Fostamatinib - Rigel Pharmaceuticals
Alternative Names: FosD; Fostamatinib disodium; Fostamatinib disodium hexahydrate; Fostamatinib sodium; R 985788; R-406/788; R-788; R-935/788; R788 sodium; R935788 sodium; Tamatinib fosdium; TAVALISSE; Tavalisse; TAVLESSELatest Information Update: 15 Feb 2024
At a glance
- Originator Rigel Pharmaceuticals
- Developer AstraZeneca; Duke University Medical Center; Grifols; JW Pharmaceutical; Kissei Pharmaceutical; Knight Therapeutics; National Heart, Lung and Blood Institute; Rigel Pharmaceuticals; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; Vanderbilt University Medical Center
- Class Anti-inflammatories; Antianaemics; Antihyperglycaemics; Antineoplastics; Antirheumatics; Oxazines; Phosphoric acid esters; Pyridines; Pyrimidines; Small molecules
- Mechanism of Action Syk kinase inhibitors
-
Orphan Drug Status
Yes - Idiopathic thrombocytopenic purpura; Autoimmune haemolytic anaemia
Orphan designation is assigned by a regulatory body to encourage companies to develop drugs for rare diseases.
- New Molecular Entity Yes
Highest Development Phases
- Marketed Idiopathic thrombocytopenic purpura
- Preregistration COVID 2019 infections
- Phase III Autoimmune haemolytic anaemia
- Phase II/III COVID-19 pneumonia
- No development reported Graft-versus-host disease; Ovarian cancer; Waldenstrom's macroglobulinaemia
- Discontinued Chronic lymphocytic leukaemia; Diffuse large B cell lymphoma; IgA nephropathy; Rheumatoid arthritis; Solid tumours; Systemic lupus erythematosus; T-cell lymphoma; Type 1 diabetes mellitus
Most Recent Events
- 06 Feb 2024 Preregistration for Idiopathic thrombocytopenic purpura in South Korea (PO), prior to February 2024 (Kissei Pharmaceutical pipeline, February 2024)
- 31 Dec 2023 Rigel Pharmaceuticals has patent protection for Fostamatinib in USA, Japan, Europe and multiple countries Worldwide
- 31 Dec 2023 Rigel Pharmaceuticals decides not to submit an Emergency Use Authorization or sNDA for COVID-2019 infections
Development Overview
Introduction
Fostamatinib is an orally administered, spleen tyrosine kinase (SYK) inhibitor, developed by Rigel Pharmaceuticals, for the treatment of idiopathic (immune) thrombocytopenic purpura (ITP), autoimmune haemolytic anaemia, and Waldenström's macroglobulinemia. Syk kinase inhibitors block release of all major downstream mediators of inflammation by activation of the IgG receptor on inflammatory cells and also hinder platelet destruction. Fostamatinib is a prodrug that is metabolised to R 406. SYK inhibition may improve outcomes in patients with COVID-19 via inhibition of key Fc gamma receptor and c-type lectin receptor (CLR) mediated drivers of pathology, such as inflammatory cytokine release by monocytes and macrophages, production of neutrophil extracellular traps (NETs) by neutrophils, and platelet aggregation. Furthermore, SYK inhibition in neutrophils and platelets may lead to decreased thromboinflammation, alleviating organ dysfunction in critically ill patients with COVID-19. The product is approved and launched in the US, Germany, the UK, Japan, Israel, France, Czech Republic, Norway, Denmark, The Netherlands, Italy, Spain and Canada for idiopathic (immune) thrombocytopenic purpura. It is registered in the EU, Iceland, Liechtenstein for Idiopathic thrombocytopenic purpura. The product is under review for the treatment of idiopathic (immune) thrombocytopenic purpura in Brazil, Argentina, South Korea, Colombia and Mexico. The drug is under regulatory review for COVID-2019 infections in the US. Early research is underway in the US for Waldenström's macroglobulinemia. Clinical development for autoimmune haemolytic anaemia and idiopathic (immune) thrombocytopenic purpura is underway in multiple countries across the world. Clinical development for pneumonia associated with COVID-2019 infections is underway in the UK and clinical development for COVID-2019 infections is underway in multiple countries.
Clinical development of fostamatinib for the treatment of IgA nephropathy, rheumatoid arthritis, diffuse large B-cell lymphoma, chronic lymphocytic leukaemia, systemic lupus erythematosus, solid tumour, T-cell lymphoma and type I diabetes mellitus was not listed on the Rigel's pipeline. It therefore appears that development for these indications was discontinued. Phase I development in graft versus host disease and ovarian cancer was conducted in the US. As at March 2021, no recent reports of development had been identified.
AstraZeneca had previously been developing fostamatinib with Rigel under a worldwide licensing agreement. However, in June 2013, AstraZeneca decided to return all rights to the compound to Rigel based on results from the phase III OSKIRA programme for treatment of rheumatoid arthritis.
As at July 2023, no recent reports of development had been identified for research development in Waldenstrom's macroglobulinaemia in USA (PO).
Company Agreements
In May 2022, Rigel Pharmaceuticals entered into a commercial license agreement with Knight Therapeutics for the commercialisation of fostamatinib in all indications in Latin America. Under the terms of agreement Rigel received a $US2.0 million upfront payment in the second quarter of 2022, with potential for up to an additional $20.0 million in regulatory and sales-based commercial milestone payments, and will receive twenty- to mid-thirty percent, tiered, escalated net sales-based royalty payments for products sold in the Knight territory. [1]
In August 2021, Inmagene and Kissei Pharmaceutical entered into an exclusive license agreement for the development and commercialization of fostamatinib in mainland China, Hong Kong and Macau. Under the terms of the agreement, Inmagene will obtain exclusive rights to develop and commercialize fostamatinib in all potential indications in China. Inmagene will bring fostamatinib to China via an accelerated development and registration pathway. In return, Kissei will receive an upfront payment and milestone payments based on the progress of development and commercialization. [2]
In June 2021, JW Pharmaceutical Corporation enter into licensing agreement with Kissei Pharmaceutical to develop and commercialize fostamatinib for the treatment of immune thrombocytopenic purpura (ITP) in South Korea. Under the terms of agreement, JW Pharmaceutical will proceed with the development, regulatory approval process, and marketing of fostamatinib in South Korea and hence strengthen its hemato-oncology product portfolio. [3]
In February 2020, Rigel Pharmaceuticals received a $US20 million payment from its collaborative partner Grifols. The payment is comprised of $US17.5 million for the European Commission's approval of the marketing authorization application for fostamatinib for the treatment of chronic immune thrombocytopenia (ITP) in adult patients who are refractory to other treatments and a $US2.5 million creditable advance royalty payment based on the terms of the collaboration agreement. Earlier, in January 2019, Rigel Pharmaceuticals entered into an exclusive license and supply agreement with Grifols to commercialise fostamatinib in all potential indications in Europe and Turkey. Under terms of the agreement, Rigel will receive a $US30 million upfront cash payment, with the potential for $US297.5 million in payments related to regulatory and commercial milestones, which includes a $US20 million payment for EMA approval of fostamatinib for the treatment of ITP. Rigel will receive significant stepped double-digit royalty payments based on tiered net sales which may reach 30% of net sales. In return, Grifols receives exclusive rights to fostamatinib in human diseases, including chronic ITP, autoimmune hemolytic anemia (AIHA), and IgA nephropathy (IgAN), in Europe and Turkey. In the event that, in 2021, after the second anniversary of the agreement, fostamatinib has not been approved by the EMA for the treatment of ITP in Europe, Grifols will have the option during a six-month time-frame to terminate the entire agreement which would terminate all their rights to ITP, AIHA, and all other indications. In this limited circumstance, Rigel will pay Grifols $US25 million and regain all rights to fostamatinib in Europe and other territories. Rigel retains the remaining global rights to fostamatinib outside the Grifols territories and those rights previously granted to Kissei Pharmaceuticals (in Japan, China, Taiwan and the Republic of Korea). [4] [5]
In October 2019, Rigel Pharmaceuticals entered into exclusive commercialisation license agreements with Medison Pharma to commercialise fostamatinib in all potential indications in Canada and Israel. Under the terms of the agreements, Rigel will receive an upfront payment of $US 5 million, including an advanced royalty payment and Rigel may receive approximately $US 35 million on achieving regulatory and commercial milestones. Rigel Pharmaceuticals will receive royalty payments starting at 30% of net sales after the fullfillment of credit for the advanced royalty payment. [6]
In October 2018, Rigel Pharmaceuticals entered into an exclusive license and supply agreement with Kissei Pharmaceuticals to develop and commercialise fostamatinib disodium hexahydrate (TAVALISSE™) in all current and potential indications in Japan, China, Taiwan and the Republic of Korea. Under the terms of the agreement, Rigel will receive an upfront cash payment of $US33 million, with the potential for an additional $US147 million in development and commercial milestone payments, and will receive product transfer price payments in the mid to upper twenty percent range based on tiered net sales for the exclusive supply of TAVALISSE. Kissei will receive exclusive rights to TAVALISSE in ITP and all future indications in Japan, China, Taiwan, and the Republic of Korea. Rigel will retain the global rights, excluding these Asian countries, to develop and commercialise TAVALISSE in ITP and any additional indications. [7]
In June 2013, Rigel announced that it will resume responsibility for the fostamatinib programme after AstraZeneca decided that it would not proceed with regulatory filings based on results from the phase III OSKIRA programme for treatment of rheumatoid arthritis (RA). Consequently, AstraZeneca were to return all rights to the compound to Rigel [8] . The companies originally entered into an exclusive worldwide licence agreement for the global development and commercialisation of fostamatinib in February 2010. AstraZeneca gained the rights to fostamatinib for RA and additional indications, and was responsible for development, regulatory filings, manufacturing, and global commercialisation. The agreement included an upfront payment of $US100 million to Rigel plus milestones and royalties on potential sales [9] [10] .
Key Development Milestones
Idiopathic thrombocytopenic purpura (ITP)
In May 2018, Rigel Pharmaceuticals launched fostamatinib disodium hexahydrate (TavalisseTM) in the US for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia (ITP) who had an insufficient response to a previous treatment [11] . Earlier, in April 2018, the US FDA approved fostamatinib disodium hexahydrate for the treatment of ITP based on results from FIT clinical programme, which includes study 047, study 048 and the open-label extension study 049, with a total of 163 ITP patients [see below], as well as safety data from over 4 600 patients from other trials of fostamatinib [12] . In October 2017, the FDA reported that it is not planning to hold an Oncology Drugs Advisory Committee meeting to discuss the NDA for fostamatinib in patients with chronic or persistent idiopathic (immune) thrombocytopenia. In April 2017, the US FDA conditionally accepted the proprietary name Tavalisse™, based on the FDA's guidance for industry, contents of a complete submission for the evaluation of proprietary names [13] [14] . In June 2017, the US FDA accepted for review Rigel's New Drug Application for fostamatinib, which was submitted in April 2017 [15] [16] [17] .
As at December 2022, TAVLESSE® (fostamatinib) is available Czech Republic, Norway, Denmark and the Netherlands for treatment of adult idiopathic (immune) thrombocytopenic purpura, in patients refractory to other treatments [18] . In September 2021, TAVLESSE® (fostamatinib) was available in France, Italy and Spain for treatment of adult idiopathic (immune) thrombocytopenic purpura, in patients refractory to other treatments [19] . In July 2020, Grifols reported that fostamatinib is available in Germany and the UK, with a phased rollout across the rest of Europe planned over the next 18 months before expanding into Turkey. Earlier in January 2020, Grifols announced that the European Commission (EC) approved the Marketing Authorization Application (MAA) which was validated earlier for fostamatinib for treatment of adult idiopathic (immune) thrombocytopenic purpura, in patients refractory to other treatments, and initiated the review process. The approval triggered a milestone payment of $US20 million to Rigel Pharmaceuticals. In May 2019, the company reported the furtherance of the MAA by responding to EMA's day-180 questions, related to the application. Further in October 2019, the Committee on Human Medicinal Products (CHMP) of the EMA adopted a positive trend vote on the MAA and in Novemebr 2019 issued the positive opinion based on the results of 163 idiopathic thrombocytopenic purpura patients from the phase III FIT clincial programme [20] [21] [22] [23] [24] [25] .
As of January 2021, TavalisseTM is commercially available for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia in Canada [26] . Health Canada, in November 2020, approved fostamatinib disodium hexahydrate (TavalisseTM) for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to other treatments [27] .
In April 2023, Kissei Pharmaceutical announced that TAVALISSE® Tab. 100mg and 150mg, for chronic idiopathic thrombocytopenic purpura launched in Japan. In March 2023, TAVALISSE® was listed on the NHI drug price list. In December 2022, Ministry of Health, Labour and Welfare (MHLW) granted manufacturing and marketing approval to Kissei Pharmaceuticals for fostamatinib (100mg and 150mg) for the treatment of chronic immune thrombocytopenic purpura (ITP). The approval was based on the results of the phase III clinical trials (Study ID: R788-1301) of fostamatinib in ITP patients in Japan and outside of Japan [see below]. Previously, in April 2022, Kissei Pharmaceutical submitted a new drug application (NDA) for approval of manufacturing and marketing in Japan for fostamatinib for chronic immune thrombocytopenic purpura (ITP). The NDA submission was based on positive results from a Japan phase III clinical trial in chronic ITP [28] [29] [30] .
In October 2022, Grifols announced that fostamatinib (TAVLESSE®) received NICE recommendations for treating refractory chronic immune thrombocytopenia [31] .
As of March 2023, TAVALISSE is commercially available for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia in Israel [32] . Earlier in November 2020, Rigel Pharmaceuticals filed a New drug Application with Israel Ministry of Health for fostamatinib for the treatment of chronic immune thrombocytopenia [27] .
As of February 2024, Kissei Pharmaceutical reported the submission of New Drug Application (NDA) for fostamatinib in the treatment of idiopathic thrombocytopenic purpura in South Korea (Kissei Pharmaceutical pipeline, February 2024).
As of December 2022, Knight therapeutics submitted for regulatory approval of fostamatinib for the treatment of idiopathic thrombocytopenic purpura in Brazil, Argentina, Colombia and Mexico [33] [34] .
In February 2020, Fostamatinib was granted orphan drug designation from the Japanese Ministry of Health, Labour and Welfare for the treatment of in chronic idiopathic thrombocytopenic purpura [5] .
In September 2015, Fostamatinib was granted orphan drug designation from the US FDA for the treatment of chronic immune thrombocytopenic purpura [35] .
In September 2023, Kissei Pharmaceutical completed a phase III clinical trials that investigated the efficacy, safety and pharmacokinetics of fostamatinib compared with placebo, and that investigated the safety and efficacy of long term dosing of fostamatinib in patients with chronic idiopathic thrombocytopenic purpura (NCT04132050; JapicCTI195001; R788-1301). The randomized, double-blind study initiated in December 2019 and enrolled 34 participants in Japan [36] . In December 2021, top-line results from the trial were released by the company [37] . In December 2023, results from the trial were presented at the 65th American Society of Hematology Annual Meeting and Exposition (ASH-Hem-2023) [38] .
In October 2019, Rigel Pharmaceuticals initiated a phase III open label extension study of fostamatinib disodium in the treatment of warm antibody autoimmune hemolytic anemia (C935788-058; EudraCT2019-001882-34; NCT04138927). The open label trial intends to enrol approximately 90 patients in the US, Australia, Austria, Belarus, Belgium, Bulgaria, France, Czech Republic, Georgia, Germany, Italy, Netherlands, Norway, Russia, Serbia, Spain, Ukraine, United Kingdom, Hungary [39] .
In September 2019, Kissei Pharmaceuticals initiated a randomised, double-blind, placebo-controlled phase III trial to investigate the safety and efficacy of orally-administered fostamatinib in adult patients with chronic immune thrombocytopenia (ITP) (Idiopathic thrombocytopenic purpura in development table) in Japan. In May 2021, Rigel Pharmaceuticals announced that the enrolment in the trial has been completed. Earlier, the Pharmaceuticals and Medical Devices Agency (PMDA) of Japan had accepted a phase III trial protocol which Kissei Pharmaceuticals had submitted in early 2019. The discussions regarding defining a regulatory path for fostamatinib in Japan were initiated with the Pharmaceuticals and Medical Devices Agency (PMDA) in May 2019 [40] [41] [24] [42] .
In December 2017, Rigel Pharmaceuticals initiated an open-label, multi-centre, expanded access study for fostamatinib in patients with immune thrombocytopenic purpura (C-935788-055; NCT03363334) [43] .
In March 2017, additional positive data from the trials were released by Rigel [44] . Earlier, in January 2017, Rigel had released data validating fostamatinib as a potential new treatment option for patients with serious ITP [45] .
In August 2016, the primary endpoint of a stable platelet response by week 24 was met, in the first of two identical phase III trials in patients with chronic ITP (Study 047; C-935788-047; EudraCT2013-005452-15; NCT02076399; FIT 1) [46] . Rigel completed the first of the two randomised, double-blind, placebo-controlled, phase III trials in April 2016. The trial evaluated the safety and efficacy of fostamatinib. Subjects were randomised in a 2:1 ratio to receive either fostamatinib or placebo for 6 months. The trial enrolled 75 patients in the US, Australia, Canada, Denmark, Hungary, Italy, the Netherlands, the UK [47] [48] [49] [50] [51] . The second trial was completed in August 2016. The trial was initiated in November 2014 and enrolled 74 patients in the US, Austria, Bulgaria, Czech Republic, Germany, Norway, Poland, Romania and Spain (Study 048; C-935788-048; EudraCT2013-005453-76; NCT02076412; FIT 2). In October 2013, Rigel announced that it had an end-of-phase II meeting with the US FDA for development of fostamatinib in ITP. In October 2016, Rigel announced results from the FIT 2 trial mentioning that the primary endpoint of stable platelet response was not met [52] [53] [54] .
In June 2020, Rigel Pharmaceuticals completed a phase III, long-term extension trial that investigated the long term safety and efficacy of fostamatinib in patients with chronic ITP who have participated in qualifying studies C935788-047 or C935788-048 (049 FIT (Fostamatinib for Immune Thrombocytopenia) Extension Study; C935788-049; 16835; NCT02077192; EudraCT2013-005454-30; Study 049). This open-label trial was initiated in July 2014, and enrolled 124 patients in the US, Australia, Austria, Bulgaria, Canada, Czech Republic, Denmark, Hungary, Italy, Netherlands, Norway, Poland, Romania, Spain and the UK. In December 2018, data from the study were presented at the 60th Annual Meeting and Exposition of the American Society of Hematology [55] [56] .
Rigel completed a proof-of-concept phase II trial of fostamatinib in adult patients in the US with chronic refractory ITP (D4300C00022; C-935788-007; NCT00706342). Data presented by the company in November 2007 demonstrated that fostamatinib improved platelet counts in these patients. A phase I trial for this indication was previously conducted by Rigel in February 2006 [57] [58] [59] .
Autoimmune haemolytic anaemia (AIHA)
In October 2022, Rigel Pharmaceuticals announced that they received guidance from the U.S. Food and Drug Administration (FDA)'s review of the company's re-analysis of data from the FORWARD phase III trial [See below] of fostamatinib for the treatment of patients with warm autoimmune hemolytic anemia (wAIHA). Based on this guidance, Rigel does not expect to file a supplemental New Drug Application (sNDA) for this indication [60] .
In May 2021, Rigel Pharmaceuticals announced that the US FDA has granted a Fast Track designation to fostamatinib for the treatment of autoimmune haemolytic anaemia [40] .
In April 2022, Rigel Pharmaceuticals completed a phase III FORWARD trial that evaluated the efficacy of fostamatinib in patients with warm antibody autoimmune haemolytic anaemia, who have failed at least one prior treatment (C-935788-057; NCT03764618). The randomised, double-blind, placebo-controlled trial was initiated in April 2019 and enrolled 90 patients in the US, Australia, Austria, Belarus, Belgium, Bulgaria, Canada, Czech Republic, Denmark, France, Georgia, Germany, Hungary, Italy, Netherlands, Norway, Romania, Russia, Serbia, Spain, UK and Ukraine [61] . In November 2021, Rigel announced the completion of enrollment of the trial [62] . In May 2019, Rigel Pharmaceuticals enrolled the first patient in the study. Prior to January 2019, the company conducted meetings with the US FDA to discuss this trial for autoimmune haemolytic anaemia. In November 2020, Rigel Pharmaceuticals reached agreement with the US FDA on the final design of this pivotal phase III FORWARD trial of fostamatinib in warm autoimmune hemolytic anaemia (AIHA). The FDA agreed to the company's proposed durable response measure for the primary efficacy endpoint and the inclusion of additional secondary endpoints. The primary efficacy endpoint is a durable response defined as a hemoglobin level = 10 g/dl with an increase from baseline of = 2 g/dl on three consecutive available visits during the 24-week treatment period, with the response not being attributed to rescue therapy [40] [63] [64] [65] [42] [66] [5] [67] [68] . As of August 2021, approximately 80 patients were enrolled in the trial [69] . In June 2022, Rigel Pharmaceuticals released efficacy and safety data from the trial [70] . In December 2022, efficacy and safety data were presented at the 64th American Society of Hematology Annual Meeting and Exposition (ASH-Hem-2022) [71] .
In January 2018, the US FDA granted Orphan Drug Designation to fostamatinib for the treatment of warm antibody autoimmune haemolytic anaemia [72] .
In October 2017, trial met pre-specified primary endpoints. In December 2019, Rigel Pharmaceuticals completed phase II proof-of-concept SOAR trial which evaluated the safety and efficacy of fostamatinib (100 mg and 150 mg) bid for the treatment of patients with warm antibody AIHA (SOAR; C-935788-053, NCT02612558). Increase in haemoglobin from baseline was the defined primary endpoint of the trial. The single-group, two-stage, Simon two-stage trial was initiated in February 2016 and enrolled approximately 26 patients in the US and Canada [73] [74] . In October 2017, Rigel Pharmaceuticals completed enrolment of 17 patients in stage I of the trial [75] [76] [77] [78] [79] [80] [81] [82] . The company commenced enrolment of approximately 20 patients in stage II of the study in late 2017. In March 2018, the company released updated efficacy results of stage 1 of the study and reported that the safety profile was consistent with the existing fostamatinib safety database [72] [83] . In June 2019, updated results from extension period of the trial were presented at the 24th Congress of the European Haematology Association Session (EHA-2019). Results were also released by the company in November 2019 [84] [85] [86] . Later in December 2019, updated safety data from the trial were released by the company [87] . In March 2022, Rigel Pharmaceuticals announced the publication of safety and efficacy data in the American Journal of Hematology from the trial [88] .
COVID-2019 infections
As of December 2023, Rigel Pharmaceuticals announced that given the end of the federal COVID-19 Public Health Emergency (PHE) in May 2023, and based on feedback from the FDA, DOD and other advisors regarding the program’s regulatory requirements, costs, timeline and potential for success, company decided not to submit an Emergency Use Authorization (EUA) or sNDA [89] . In August 2021, Rigel Pharmaceuticals announced that, the USFDA declined to issue emergency use authorization (EUA) for fostamatinib for the treatment of COVID-19 in hospitalized adults.The USFDA stated that, clinical data submitted in by the company for EUA approval was insufficient for an emergency use authorization (EUA). Company announced that, based on phase III data [See below] company plans to resubmit EUA application. In May 2021, Rigel Pharmaceuticals filed an application for the emergency use authorization (EUA) from the US FDA for fostamatinib, in hospitalized patients diagnosed with COVID-2019 infections. The application contains data from it previously completed National Heart, Lung, and Blood Institute (NHLBI) sponsored phase II trial (see below) [90] [91] [69] .
In September 2023, the Data and Safety Monitoring Board (DSMB) recommended that the fostamatinib study arm of the ACTIV-4 Host Tissue (NECTAR) platform cease enrollment as no safety concerns were identified. The National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health, concurs with the DSMB's recommendations and has asked the trial investigators to cease enrollment, complete follow-up for participants already enrolled, and complete study closeout. The company is planning to analyzed and disseminated full study data, previously planned [92] [93] . In December 2023, Vanderbilt University Medical Center completed the phase II/III NECTAR ACTIV-4 Host Tissue trial (Accelerating COVID-19 Therapeutic Interventions and Vaccines) (ACTIV) which was designed to evaluate the effect of fostamatinib in the host tissue outcomes against COVID-2019 infections. Therapeutic goals for patients hospitalized for COVID-19 include hastening recovery and preventing progression to critical illness, multiorgan failure, or death (NCT04924660; 210982; EudraCT2022-000715-31). The randomized, double blind, placebo controlled trial was initiated in July 2021 and enrolled 871 participants in the US and Italy [90] [93] .
In October 2023, Rigel Pharmaceuticals announced that the trial met its primary endpoint. In September 2022, Rigel Pharmaceuticals completed phase III FOCUS trial to evaluate the efficacy and safety of fostamatinib in COVID-19 patients (NCT04629703; C-935788-061). The randomised, double-blind trial was initiated in March 2021 and enrolled 280 patients in the US, Argentina, Brazil and Mexico [94] [95] . As of August 2021, approximately 150 patients were enrolled in the trial. As of August 2021, approximately 176 patients were enrolled in the study, company plans to complete the enrolment by year-end of 2021. In September 2021, data from study was presented at the IDWeek 2021 (IDW-2021) [96] [90] [69] . In July 2022, Rigel Pharmaceuticals announced the completion of enrolment with 280 patients in the trial [97] [1] [98] . In November 2022, company released the top-line safety and efficacy results from the trial. The Other Transaction Authority (OTA) agreement for this study was executed by the Defense Department's Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND), in collaboration with the U.S. Army Contracting Command – Aberdeen Proving Ground, using Coronavirus Aid, Relief, and Economic Security (CARES) Act funding [99] . In October 2023, the Company presented results of the trial at the ID Week 2023 (IDW- 2023) [100] [101]
In April 2021, Rigel Pharmaceuticals announced that the trial met its primary endpoint of safety. In May 2021, Rigel Pharmaceuticals completed a phase II trial and met its primary endpoint of safety and showed broad and consistent improvement in efficacy endpoints, which included mortality, ordinal scale assessment and number of days in the ICU. In September 2020, Rigel Pharmaceuticals in collaboration with National Heart, Lung, and Blood Institute (NHLBI) and Inova® Health System had initiated a phase II trial to evaluate the safety and efficacy of orally administered fostamatinib in hospitalised patients with COVID-2019 infection (NCT04579393; 10000110; 000110-H). The randomised, double-blind, placebo-controlled trial enrolled 62 patients who are a 5 to 7 on the 8-point ordinal scale (requiring supplemental oxygen via nasal canula or non-invasive ventilation, requiring mechanical ventilation or extracorporeal membrane oxygenation) in the US. The secondary objective will be to assess the early efficacy and clinically relevant measures of disease progression. In March 2021, the enrolment was completed in the trial. The data obtained from the trial will be utilised for a discussion between the company and the US FDA for an Emergency Use Authorisation (EUA) for fostamatinib for the treatment of hospitalised COVID-19 patients. In April 2021, Rigel Pharmaceuticals released top-line results from the trial [102] [40] [103] [104] [105] . Later, in September 2021, the company published topline efficacy and adverse events data in Clinical Infectious Diseases, an official publication of the Infectious Disease Society of America [106] .
Adult respiratory syndrome or pneumonia (associated with COVID-2019 infections)
In July 2020, Rigel Pharmaceuticals initiated an investigator-sponsored phase II/III MATIS trial to evaluate the efficacy of ruxolitinib [see AdisInisight drug profile 800026694] plus best supportive treatment (BST) versus fostamatinib plus BST versus BST, for the treatment of COVID-19 pneumonia (20HH5926; EudraCT2020-001750-22; NCT04581954). In the two-stage open label, controlled clinical trial, the patients will be randomized (1:1:1) to fostamatinib, ruxolitinib, or standard of care. The primary objective will be to determine the efficacy of fostamatinib and the efficacy of ruxolitinib compared to standard of care to reduce the proportion of hospitalized patients progressing from mild or moderate to severe COVID-19 pneumonia. Rigel will provide support for this trial along with Novartis and is being conducted by Imperial College London. The trial intends enroll 186 patients in the UK [107] [108] .
In in vitro studies, R406 showed activity of blocking macrophage hyperinflammatory responses to a combination of immune complexes formed by anti-Spike IgG in serum from severe COVID-19 patients [109] .
Rigel Pharmaceuticals believe that inhibition of SYK kinase with fostamatinib could inhibit release of harmful cytokines in response to SARS-CoV-2 which will be beneficial for the treatment of pneumonia or acute respiratory distress syndrome in in patients with COVID-2019 infections. For the development, Rigel is actively seeking opportunities to collaborate with research institutes [66] .
Ovarian cancer
In February 2018, Rigel Pharmaceuticals, in collaboration with Sidney Kimmel Comprehensive Cancer Center, initiated a phase I trial to determine the maximally tolerated dose (MTD) of fostamatinib when administered with weekly paclitaxel in women with recurrent platinum-resistant ovarian, fallopian tube or primary peritoneal cancer (J1708; NCT03246074; IRB00110406). The open-label, non-randomized, dose-escalation study will enrol 27 patients in the US. In June 2023, efficacy and adverse events from phase I trial in ovarian cancer were presented at 59th Annual Meeting of the American Society of Clinical Oncology (ASCO-2023) [110] [111] .
Waldenstrom's macroglobulinaemia
In June 2019, preclinical data for Waldenstrom's macroglobulinaemia were presented at the 55th Annual Meeting of the American Society of Clinical Oncology (ASCO-2019) [112] .
IgA nephropathy
As at November 2018, IgA nephropathy is not listed as active development indication for fostamatinib, on Rigel Pharmaceuticals' pipeline. Hence the development has been discontinued.
In April 2018, Rigel Pharmaceuticals released top line data from the proof-of-concept, phase II trial which showed that the trial did not attain statistical significance for its primary endpoint [113] . Rigel had initiated the randomised, double-blind, placebo-controlled phase II SIGN trial in October 2014 to assess the safety and efficacy of ascending doses of fostamatinib in the treatment of IgA nephropathy (C-935788-050; EudraCT2014-000331-16; NCT02112838). The primary endpoint is the mean change in renal function, histology and proteinuria at 24 weeks from baseline. In August 2017, the trial completed enrolment of 76 patients, in the US, Austria, Germany, Hong Kong, Singapore, Switzerland, Taiwan and the United Kingdom. Data from the completed first cohort (fostamatinib 100mg BID, n = 26; placebo n = 12) demonstrated a favourable 24-week safety profile, with a trend towards greater reductions in proteinuria in fostamatinib-treated subjects, versus those who received placebo. Further data are expected later in 2017. The company completed the enrolment in the second cohort (fostamatinib 150mg) in 2017 [78] [81] [114] [115] [48] [116] [117] . The company also planned a phase II extension trial of fostamatinib in patients who participated in study C-935788-050 (C-935788-051; NCT02433236). This non-randomised trial was expected to enrol approximately 25 patients in the US, Austria, Germany, Hong Kong, Singapore, Switzerland, Taiwan, United Kingdom; however, the study was withdrawn prior to enrolment [118] .
Rheumatoid arthritis (RA)
Rigel reported in June 2013 that it was reviewing the results of AstraZeneca's extensive development efforts with fostamatinib to determine the appropriate path forward, after AstraZeneca determined that it would not proceed with regulatory filings for the indication. AstraZeneca's decision was based on results from the phase III OSKIRA (Oral Syk Inhibition in Rheumatoid Arthritis) programme, which had been initiated in September 2010 [8] [119] . Since at least October 2013, RA has not been listed on Rigel's pipeline and it appears that the company has decided to discontinue development of fostamatinib in this indication. The OSKIRA programme consisted of four phase III trials, which enrolled patients throughout the US, Canada, Europe, Australia, Latin America, South Africa, India and the Israel (NCT01197521, NCT01197534, NCT01197755, NCT01264770). The programme also included a long-term extension study (OSKIRA-X; NCT01242514) [120] [121] . Initiation of the phase III OSKIRA programme triggered two milestone payments totalling $US25 million from AstraZeneca to Rigel, for the initiation of the trials and completion of the transfer of the programme to AstraZeneca [122] [123] [119] [124] [10] [125] . AstraZeneca terminated the OSKIRA programme in the third quarter of 2013, following its decision to discontinue its involvement in the development of fostamatinib.
In April 2013, top-line results from the first phase III trial (OSKIRA-1) were released, which showed that the trial met one of its primary endpoints, the American College of Rheumatology 20% response rate (ACR20) (NCT01197521). However, the other primary endpoint, modified Total Sharp Score (mTSS) was not met. The trial evaluated the safety and efficacy of two dosing regimens of fostamatinib in patients with rheumatoid arthritis who had an inadequate response to methotrexate [126] . The randomised, double-blind, placebo-controlled trial enrolled 923 patients and was completed in November 2012 [120] [127] . The second trial (OSKIRA-2) is comparing the effectiveness of two dosing regimens of fostamatinib with placebo and enrolled 913 patients with RA who were not responding to DMARD treatment (NCT01197534) [128] . The OSKIRA-3 trial, completed in February 2013, was investigating the drug in 322 patients with RA who were on methotrexate and had previously had a poor response to a TNF-alpha antagonist (NCT01197755) [129] . Results from OSKIRA-2 and OSKIRA-3 were expected during the second quarter of 2013 [126] .
Top-line results released in December 2012 showed that fostamatinib met one of two primary endpoints in the OSKIRA-4 study. The 6-month phase IIb trial compared three dose regimens of fostamatinib monotherapy with adalimumab monotherapy in DMARD-naïve patients (n=280) with active RA (NCT01264770) [121] . Fostamatinib was superior to placebo at 6 weeks in change from baseline in DAS28 score (first primary objective) but all dose regimens did not demonstrate non-inferiority against adalimumab monotherapy at 24 weeks (second primary objective) [125] .
In January 2013, AstraZeneca completed a phase II trial that investigated the incidence of hypertension in patients with active rheumatoid arthritis receiving fostamatinib in combination with a disease-modifying anti-rheumatic drug (Oskira ABPM; NCT01563978). The trial enrolled 135 patients in the US, the EU (Bulgaria, Czech Republic, Germany and Poland), Ukraine, South America and South Africa [130] . Another phase II study was investigating the efficacy and tolerability of fostamatinib in combination with methotrexate in approximately patients with active rheumatoid arthritis and an inadequate response to methotrexate in Asia (OSKIRA-Asia-1; NCT01569074). However, the trial was terminated following AstraZeneca's decision to discontinue development in RA. The trial had enrolled 163 patients in Japan, Taiwan, Thailand, South Korea, Hong Kong and Vietnam [131] . An open-label, long-term extension for this trial was also terminated (OSKIRA-Asia-1X; NCT01640054) [132] .
Two phase IIb trials of fostamatinib were initiated in the US, the EU and Latin America in June 2008. The first trial has been completed and positive results have been reported (TASKi-2; NCT00665925). In this double-blind trial, 457 patients who had previously failed methotrexate monotherapy were randomised to receive either fostamatinib 100mg twice-daily; 150mg once-daily; or placebo, for 6 months. In addition, all patients received a stable dose of methotrexate throughout the trial [133] [134] . The second trial has also been completed, but it failed to meet its efficacy endpoints (TASKi-3; NCT00665626). This trial evaluated fostamatinib 100mg twice-daily versus placebo, in 219 patients with RA who had failed at least one marketed biologic agent, including anti-TNF injectables. During the three-month trial, patients could continue on their stable dose of methotrexate and/or other non-biologic therapies [135] . The primary endpoints of TASKi-2 and TASKi-3 were to measure the efficacy of fostamatinib as determined by the ACR20 scores at six months and three months, respectively. TASKi 3 also included measurement of changes in bone morphology by MRI [136] [137] [138] [139] .
A randomised, double-blind, placebo-controlled phase IIa study, evaluating up to three doses of fostamatinib in patients with RA on chronic methotrexate therapy, has been completed (TASKi-1; NCT00326339). The study showed that orally administered fostamatinib at doses of 100mg twice daily and 150mg twice daily produced significant improvements in RA symptoms [140] [139] [141] [142] [143] .
AstraZeneca terminated an open-label, multicentre phase II extension study in patients with rheumatoid arthritis who have completed the treatment phase of a study sponsored by Rigel (NCT00805467). This was following AstraZeneca's decision to return its rights for fostamatinib to Rigel [144] .
In December 2005, Rigel initiated a phase I trial of fostamatinib in combination with methotrexate in patients with rheumatoid arthritis. Results showed that fostamatinib was well-tolerated [145] [146] .
B-cell lymphoma
In October 2013, AstraZeneca completed a phase II trial of fostamatinib in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) (NCT01499303). The open-label trial assessed the efficacy of fostamatinib (200mg twice-daily) in 101 patients in the US and the UK [147] [142] [148] . However, in line with AstraZeneca's withdrawal from further development of fostamatinib, development in this indication has been discontinued.
In October 2010, AstraZeneca completed a phase I/II trial to investigate the effect of fostamatinib in patients with B-cell lymphoma (D4300C00023; NCT00446095). The two part trial was initiated in April 2007 and enrolled 81 patients with diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, non-Hodgkin's lymphoma and chronic lymphocytic leukaemia in the US [149] .
Chronic lymphocytic leukaemia
The Policlinico Universitario Agostino Gemelli hospital in Italy initiated an uncontrolled phase II trial in June 2009 to evaluate fostamatinib as a treatment for residual disease after chemotherapy in patients with chronic lymphocytic leukaemia (EudraCT2009-009034-32). However, the trial was discontinued.
In an in vitro study, fostamatinib was shown to be effective in disrupting different B-cell receptor-derived responses, suggesting its potential utility in the treatment of chronic lymphocytic leukaemia [150] . Rigel had previously reported promising data in December 2006 in a preclinical model of leukaemia [151] . However, as this indication no longer appears on Rigel's pipeline, development appears to have been discontinued.
Solid tumours
The National Cancer Institute completed a phase II trial of fostamatinib in the USA for the treatment of advanced solid tumours (090138; 09-C-0138; NCT00923481). The trial included 37 patients with advanced colorectal cancer, thyroid cancer, non-small cell lung cancer, hepatocellular cancer, head and neck cancer or renal cell cancer that had not responded to at least one line of anticancer therapy. Patients received oral fostamatinib twice-daily, in 28-day treatment cycles; treatment continued until the occurrence of disease progression or patient or physician withdrawal [152] . Rigel supplied the drug and received clinical data and trial results. However, no recent development for this indication has been reported [153] .
Systemic lupus erythematosus
Rigel initiated a phase II trial in the second half of 2008 to evaluate the safety and efficacy of fostamatinib for the treatment of SLE (SOLEIL; C-935788-015; 2008-004472-50; NCT00752999). However, this trial was suspended in December 2008 and subsequently terminated in May 2010 [154] .
Fostamatinib successfully treated lupus-prone mice and significantly improved their survival [155] .
T-cell lymphoma
Rigel completed a phase II trial of fostamatinib in patients with refractory or relapsed peripheral T-cell lymphoma (D4300C00024;C-935788-017; NCT00798096). This study assessed the efficacy of the drug in 61 patients from the USA and Canada who had previously failed to respond to standard of care treatment [156] [157] . However, this indication no longer appears on Rigel's pipeline, and development in this area appears to have been discontinued.
Type 1 diabetes mellitus
In April 2008, Rigel presented results at the American Association of Immunologists meeting from a preclinical study that showed the potential of fostamatinib in delaying the onset of type 1 diabetes mellitus and prolonging the survival of diabetic mice [158] . No further development was reported in this indication, and is therefore assumed to have been discontinued.
Phase I trials
In March 2013, AstraZeneca completed a phase I trial in the US that assessed the bioequivalence of 13% versus 38% drug-loaded fostamatinib tablet formulations at 100 and 150mg doses in 88 healthy volunteers (D4300C00020; NCT01645085) [159] .
AstraZeneca completed several phase I trials in volunteers to investigate potential drug interactions between fostamatinib and other drugs, including rifampicin (NCT01336218) [160] , pioglitazone (NCT01309854) [161] , ranitidine (NCT01682408) [162] , warfarin (NCT01311622) [163] , digoxin (NCT01355354) [164] , rosuvastatin and simvastatin (NCT01725230) [165] , and ethinylestradiol/levonorgestrel (Microgynon®) (NCT01276262) [166] .
The company also investigated the tolerability and pharmacokinetics of fostamatinib in specific populations, including Japanese volunteers (NCT01608542; NCT01167868) [167] [168] , patients with impaired liver function (NCT01222455), and patients with impaired renal function (NCT01245790) [169] .
AstraZeneca completed several phase I trials in volunteers to assess the bioavailability of oral fostamatinib tablets (50 – 150mg) (NCT01208155; NCT01387308) [170] [171] . The absolute bioavailability of oral fostamatinib in relation to an intravenous micro-tracer dose of the radiolabelled R 406 (the major metabolite of the prodrug fostamatinib) was assessed in a trial that was completed in August 2012 (NCT01598571). This non-randomised trial involved 37 male volunteers from the UK [172] .
In February 2009, Rigel reported the results of a completed QT/QTc safety study of fostamatinib in healthy volunteers. The results confirmed that fostamatinib does not elicit a QT/QTc signal. The trial protocol was pre-reviewed by the US FDA [137] .
NIO-sponsored trials
In February 2022, Duke University completed a phase I trial which assessed the safety and efficacy of fostamatinib (100mg qd, 150mg qd, or 100mg bid) in prevention of chronic graft versus host disease (cGVHD) after allogeneic stem cell transplant (Pro000164227; NCT02611063). The single-group, open-label trial was initiated in January 2016, and enrolled 22 patients in the US [173] .
Financng information
In January 2021, Rigel Pharmaceuticals was awarded $US16.5 million by the US Department of Defense's (DOD) Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND) to support Rigel's ongoing phase III trial to evaluate the safety and efficacy of fostamatinib in hospitalised COVID-19 patients [see above] [94] .
Patent Information
As of December 2023, Fostamatinib is covered as a composition of matter in the US Patent No. 7 449 458 for which the US Patent and Trademark Office granted a patent term extension on December 21, 2023. Accordingly, the term of the US 7 449 458 patent has been extended to September 2031. Additional patents covering fostamatinib composition of matter, methods for use, formulations, methods for making and intermediates expire at various dates from 2023 to 2041. Company has owned 7 pending patent applications and 43 issued and active patents in the US for fostamatinib. Corresponding applications have been filed in foreign jurisdictions under the PCT, and are at various stages of prosecution. Of note, patents covering fostamatinib as a composition of matter and in compositions for use treating various diseases are issued in Europe and Japan, as well as in other jurisdictions abroad [89] .
As at May 2021, Rigel pharmaceuticals has patent protection for fostamatinib covering composition of matter patent in the US with an expected expiration in September 2031, with a patent term adjustment and extension rules [174] .
As at May 2021, Rigel pharmaceuticals has patent protection for fostamatinib covering broader composition of matter claims in a US with expiration date in March 2026, with a patent term adjustment [174] .
As at May 2021, Rigel pharmaceuticals has patent protection for additional patents covering fostamatinib composition of matter, methods for use, formulations, methods for making with expiry in 2023, 2026, 2028, 2030, 2032 and 2034, in the US [174] .
As at May 2021, Rigel pharmaceuticals has pending patents in foreign jurisdictions under the PCT, and are at various stages of prosecution [174] .
As at May 2021, Rigel pharmaceuticals has patent protection for fostamatinib covering composition of matter and in compositions for use treating various diseases in the EU [174] .
In April 2017, Rigel pharmaceuticals applied to the US Patent Office (USPTO) for obtaining federal registration of Tavalisse™ mark [14] .
In March 2016, Rigel pharmaceuticals reported that the company has a patent covering the composition of R 406 in the US and the patent is expected to expire in February 2025, inclusive of a patent term adjustment. The company also has two patents issued in the US, for methods of using R 406 to treat various indications and compositions of matter covering certain intermediates used to make R406. These patents also cover broader composition of matter and are expected to expire in February 2023 and July 2024. Corresponding applications have also been filed in other jurisdictions under the patent cooperation treaty (PCT) (Rigel Pharmaceuticals 10-K, March 2016).
Rigel has a composition of matter patent in the US with an expiry date in September 2026. Fostamatinib is also covered under broader composition of matter claims in a US issued patent which expires in 2026. Methods of using fostamatinib to treat various indications, methods of making fostamatinib, and compositions of matter covering certain intermediates used to make fostamatinib are also covered, in three US issued patents with expiry dates ranging from April 2023 to June 2026. These expiration dates take into account patent term adjustments.
A patent covering fostamatinib as a composition of matter and in compositions for use treating various diseases has been granted by the European Patent Office.
Drug Properties & Chemical Synopsis
- Route of administration PO
- Formulation Tablet, unspecified
- Class Anti-inflammatories, Antianaemics, Antihyperglycaemics, Antineoplastics, Antirheumatics, Oxazines, Phosphoric acid esters, Pyridines, Pyrimidines, Small molecules
- Target Syk kinase
- Mechanism of Action Syk kinase inhibitors
-
WHO ATC code
A10X (Other Drugs Used in Diabetes)
B02B-X09 (Fostamatinib)
B03X (Other Antianemic Preparations)
L01 (Antineoplastic Agents)
L04A (Immunosuppressants)
M01 (Antiinflammatory and Antirheumatic Products)
-
EPhMRA code
A10X (Other Drugs Used in Diabetes)
B3X (Other Anti-Anaemic Products, Including Folic Acid, Folinic Acid)
L1 (Antineoplastics)
L4X (Other Immunosuppressants)
M1 (Anti-Inflammatory and Anti-Rheumatic Products)
- Chemical name 2H-Pyrido[3,2-b]-1,4-oxazin-3(4H)-one, 6-[[5-fluoro-2-[(3,4,5-trimethoxyphenyl)amino]- 4-pyrimidinyl]amino]-2,2-dimethyl-4-[(phosphonooxy)methyl]-, disodium salt, hexahydrate
- Molecular formula C23 H24 F N6 Na2 O9 P . 6 H2 O
- SMILES [Na+].[Na+].O.O.O.O.O.O.P(=O)(OCN1C2C(OC(C1=O)(C)C)=CC=C(N=2)NC1=NC(=NC=C1F)NC1C=C(C(=C(C=1)OC)OC)OC)([O-])[O-]
-
Chemical Structure
- CAS Registry Number 914295-16-2
Biomarkers Sourced From Trials
| Indication | Biomarker Function | Biomarker Name | Number of Trials |
|---|---|---|---|
|
B-cell lymphoma |
Arm Group Description |
Mannitol |
|
|
B-cell lymphoma |
Eligibility Criteria |
VKORC1 FSH CYP2C9 |
|
|
B-cell lymphoma |
Outcome Measure |
sex hormone-binding globulin Progesterone FSH |
|
|
chronic lymphocytic leukaemia |
Eligibility Criteria |
VKORC1 CYP2C9 |
|
|
chronic lymphocytic leukaemia |
Outcome Measure |
sex hormone-binding globulin Progesterone FSH |
|
|
colorectal cancer |
Detailed Description |
RAC-alpha serine/threonine-protein kinase (AKT) MAPK1 EPH receptor B2 |
|
|
cOVID 2019 infections |
Arm Group Description |
ACE2 |
|
|
cOVID 2019 infections |
Official Title |
Renin Aldosterone |
|
|
cOVID 2019 infections |
Outcome Measure |
Interleukin-6 (IL-6) Fibrinogen Ferritin D-dimer Cardiac Troponin I C-reactive protein (CRP) BNP ACE2 |
|
|
COVID-19 pneumonia |
Detailed Description |
Lactate dehydrogenase (LDH) Interleukin-6 (IL-6) FOS Ferritin D-dimer C-reactive protein (CRP) |
|
|
COVID-19 pneumonia |
Eligibility Criteria |
C-reactive protein (CRP) |
|
|
COVID-19 respiratory infection |
Outcome Measure |
Interleukin-6 (IL-6) Fibrinogen Ferritin D-dimer C-reactive protein (CRP) |
|
|
duodenal ulcer |
Arm Group Description |
Mannitol |
|
|
gastric ulcer |
Arm Group Description |
Mannitol |
|
|
gastro-oesophageal reflux |
Arm Group Description |
Mannitol |
|
|
graft-versus-host disease |
Detailed Description |
B-cell linker |
|
|
head and neck cancer |
Detailed Description |
RAC-alpha serine/threonine-protein kinase (AKT) MAPK1 EPH receptor B2 |
|
|
Hidradenitis suppurativa |
Detailed Description |
T-cell receptor T3 delta chain (CD3d) T-cell receptor CD3-epsilon (CD3e) Syndecan-1 (SDC1 Elastase, neutrophil Elastase auto-antibodies Cytokeratin 20 CD3 gamma chain (CD3G) B-lymphocyte antigen CD20 |
|
|
Hidradenitis suppurativa |
Outcome Measure |
T-cell receptor T3 delta chain (CD3d) T-cell receptor CD3-epsilon (CD3e) Syndecan-1 (SDC1 Elastase, neutrophil Elastase auto-antibodies Cytokeratin 20 CD3 gamma chain (CD3G) B-lymphocyte antigen CD20 |
|
|
IgA nephropathy |
Outcome Measure |
Creatinine |
|
|
liver cancer |
Detailed Description |
RAC-alpha serine/threonine-protein kinase (AKT) MAPK1 EPH receptor B2 |
|
|
non-small cell lung cancer |
Detailed Description |
RAC-alpha serine/threonine-protein kinase (AKT) MAPK1 EPH receptor B2 |
|
|
Phaeochromocytoma |
Detailed Description |
RAC-alpha serine/threonine-protein kinase (AKT) MAPK1 EPH receptor B2 |
|
|
pregnancy |
Outcome Measure |
sex hormone-binding globulin Progesterone FSH |
|
|
renal cancer |
Detailed Description |
RAC-alpha serine/threonine-protein kinase (AKT) MAPK1 EPH receptor B2 |
|
|
rheumatoid arthritis |
Outcome Measure |
sex hormone-binding globulin Progesterone FSH Estrogen receptor alpha (ER alpha) CD95 (APO-1/Fas) C-reactive protein (CRP) Alkaline phosphatase (ALPL) acrosin |
|
|
rheumatoid arthritis |
Brief Title |
Tumor necrosis factor alpha (TNF-alpha) |
|
|
rheumatoid arthritis |
Arm Group Description |
Mannitol |
|
|
rheumatoid arthritis |
Eligibility Criteria |
VKORC1 Rheumatoid factor FSH CYP2C9 CCP antibodies C-reactive protein (CRP) |
|
|
rheumatoid arthritis |
Official Title |
Tumor necrosis factor alpha (TNF-alpha) |
|
|
solid tumours |
Arm Group Description |
Mannitol |
|
|
solid tumours |
Detailed Description |
RAC-alpha serine/threonine-protein kinase (AKT) MAPK1 EPH receptor B2 |
|
|
solid tumours |
Eligibility Criteria |
VKORC1 CYP2C9 |
|
|
solid tumours |
Outcome Measure |
sex hormone-binding globulin Progesterone FSH |
|
|
T-cell lymphoma |
Eligibility Criteria |
VKORC1 CYP2C9 |
|
|
T-cell lymphoma |
Outcome Measure |
sex hormone-binding globulin Progesterone FSH |
|
|
thromboembolism |
Eligibility Criteria |
VKORC1 CYP2C9 |
|
|
thyroid cancer |
Detailed Description |
RAC-alpha serine/threonine-protein kinase (AKT) MAPK1 EPH receptor B2 |
|
|
type 1 diabetes mellitus |
Eligibility Criteria |
VKORC1 CYP2C9 |
|
|
type 1 diabetes mellitus |
Outcome Measure |
sex hormone-binding globulin Progesterone FSH |
Biomarker
| Drug Name | Biomarker Name | Biomarker Function |
|---|---|---|
| Fostamatinib - Rigel Pharmaceuticals | ACE2 | Arm Group Description, Outcome Measure |
| acrosin | Outcome Measure | |
| Aldosterone | Official Title | |
| Alkaline phosphatase (ALPL) | Outcome Measure | |
| B-cell linker | Detailed Description | |
| B-lymphocyte antigen CD20 | Detailed Description, Outcome Measure | |
| BNP | Outcome Measure | |
| C-reactive protein (CRP) | Detailed Description, Eligibility Criteria, Outcome Measure | |
| Cardiac Troponin I | Outcome Measure | |
| CCP antibodies | Eligibility Criteria | |
| CD3 gamma chain (CD3G) | Detailed Description, Outcome Measure | |
| CD95 (APO-1/Fas) | Outcome Measure | |
| Creatinine | Outcome Measure | |
| CYP2C9 | Eligibility Criteria | |
| Cytokeratin 20 | Detailed Description, Outcome Measure | |
| D-dimer | Detailed Description, Outcome Measure | |
| Elastase auto-antibodies | Detailed Description, Outcome Measure | |
| Elastase, neutrophil | Detailed Description, Outcome Measure | |
| EPH receptor B2 | Detailed Description | |
| Estrogen receptor alpha (ER alpha) | Outcome Measure | |
| Ferritin | Detailed Description, Outcome Measure | |
| Fibrinogen | Outcome Measure | |
| FOS | Detailed Description | |
| FSH | Eligibility Criteria, Outcome Measure | |
| Interleukin-6 (IL-6) | Detailed Description, Outcome Measure | |
| Lactate dehydrogenase (LDH) | Detailed Description | |
| Mannitol | Arm Group Description | |
| MAPK1 | Detailed Description | |
| Progesterone | Outcome Measure | |
| RAC-alpha serine/threonine-protein kinase (AKT) | Detailed Description | |
| Renin | Official Title | |
| Rheumatoid factor | Eligibility Criteria | |
| sex hormone-binding globulin | Outcome Measure | |
| Syndecan-1 (SDC1 | Detailed Description, Outcome Measure | |
| T-cell receptor CD3-epsilon (CD3e) | Detailed Description, Outcome Measure | |
| T-cell receptor T3 delta chain (CD3d) | Detailed Description, Outcome Measure | |
| Tumor necrosis factor alpha (TNF-alpha) | Brief Title, Official Title | |
| VKORC1 | Eligibility Criteria |
Development Status
Summary Table
| Indication | Qualifier | Patient Segment | Phase | Countries | Route / Formulation | Developers | Event Date |
|---|---|---|---|---|---|---|---|
| Autoimmune haemolytic anaemia | - | Treatment-experienced | Phase III | Australia, Austria, Belarus, Belgium, Bulgaria, Canada, Czech Republic, Denmark, France, Georgia, Germany, Hungary, Italy, Netherlands, Norway, Romania, Russia, Serbia, Spain, USA (fast track), Ukraine, United Kingdom | PO / unspecified | Rigel Pharmaceuticals | 04 Apr 2019 |
| Autoimmune haemolytic anaemia | - | - | Phase II | Canada | PO / unspecified | Rigel Pharmaceuticals | 25 Feb 2016 |
| COVID 2019 infections | in hospitalised patients | Adjunctive treatment | Preregistration | USA | PO / Tablet | Rigel Pharmaceuticals | 31 May 2021 |
| COVID 2019 infections | - | Adjunctive treatment | Phase III | Argentina, Brazil, Mexico | PO / Tablet | Rigel Pharmaceuticals | 30 Nov 2021 |
| COVID 2019 infections | - | - | Phase II/III | Italy | PO / Tablet | Vanderbilt University Medical Center | 24 Aug 2022 |
| COVID 2019 infections | - | - | Phase II/III | USA | PO / Tablet | National Heart, Lung and Blood Institute, Vanderbilt University Medical Center, Rigel Pharmaceuticals | 15 Jul 2021 |
| COVID-19 pneumonia | - | - | Phase II/III | United Kingdom | PO / Tablet | Rigel Pharmaceuticals | 14 Jul 2020 |
| Chronic lymphocytic leukaemia | - | Adjuvant therapy | Discontinued (II) | Italy | PO / Tablet | Rigel Pharmaceuticals | 29 Oct 2013 |
| Diffuse large B cell lymphoma | - | - | Discontinued (II) | USA, United Kingdom | PO / Tablet | AstraZeneca, Rigel Pharmaceuticals | 29 Oct 2013 |
| Graft-versus-host disease | - | - | No development reported (I) | USA | PO / unspecified | Duke University Medical Center | 28 Jan 2021 |
| Idiopathic thrombocytopenic purpura | - | - | Marketed | Japan | PO / Tablet | Kissei Pharmaceutical | 06 Apr 2023 |
| Idiopathic thrombocytopenic purpura | - | Treatment-experienced | Marketed | Czech Republic, Denmark, France, Germany, Italy, Netherlands, Spain, United Kingdom | PO / Tablet | Grifols | 31 Dec 2022 |
| Idiopathic thrombocytopenic purpura | Chronic immune thrombocytopenic purpura | Treatment-experienced | Marketed | Canada, Israel, Norway, USA | PO / Tablet | Rigel Pharmaceuticals | 28 Mar 2023 |
| Idiopathic thrombocytopenic purpura | - | Treatment-experienced | Registered | European Union, Iceland, Liechtenstein | PO / Tablet | Rigel Pharmaceuticals | 16 Jan 2020 |
| Idiopathic thrombocytopenic purpura | - | - | Preregistration | Mexico | PO / unspecified | Knight Therapeutics | 31 Dec 2022 |
| Idiopathic thrombocytopenic purpura | - | - | Preregistration | Argentina, Brazil, Colombia | PO / Tablet | Knight Therapeutics | 31 Dec 2022 |
| Idiopathic thrombocytopenic purpura | - | - | Preregistration | South Korea | PO / Tablet | JW Pharmaceutical, Kissei Pharmaceutical | 06 Feb 2024 |
| IgA nephropathy | - | - | Discontinued (II) | Austria, Germany, Hong Kong, Singapore, Switzerland, Taiwan, USA, United Kingdom | PO / Tablet | Rigel Pharmaceuticals | 21 Nov 2018 |
| Ovarian cancer | - | Combination therapy, In adults, In the elderly, Recurrent, Second-line therapy or greater | No development reported (I) | USA | PO / Tablet | Rigel Pharmaceuticals, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | 28 Mar 2021 |
| Rheumatoid arthritis | - | - | Discontinued (III) | Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, Chile, Colombia, Czech Republic, Estonia, France, Germany, Hungary, India, Israel, Italy, Latvia, Lithuania, Mexico, Netherlands, Peru, Poland, Portugal, Romania, Russia, Serbia, Slovakia, South Africa, Spain, USA, Ukraine, United Kingdom | PO / Tablet | Rigel Pharmaceuticals | 29 Oct 2013 |
| Rheumatoid arthritis | - | - | Discontinued (II) | Hong Kong, Japan, South Korea, Taiwan, Thailand, Vietnam | PO / Tablet | Rigel Pharmaceuticals | 29 Oct 2013 |
| Solid tumours | - | Late-stage disease | Discontinued (II) | USA | PO / Tablet | Rigel Pharmaceuticals | 29 Oct 2013 |
| Systemic lupus erythematosus | - | - | Discontinued (II) | USA | PO / Tablet | Rigel Pharmaceuticals | 20 May 2010 |
| T-cell lymphoma | - | - | Discontinued (II) | Canada, USA | PO / Tablet | Rigel Pharmaceuticals | 12 Apr 2013 |
| Type 1 diabetes mellitus | - | - | Discontinued (Preclinical) | USA | PO / Tablet | Rigel Pharmaceuticals | 12 Apr 2013 |
| Waldenstrom's macroglobulinaemia | - | - | No development reported (Research) | USA | PO / unspecified | Rigel Pharmaceuticals | 28 Jul 2023 |
Priority Development Status
| Type | Region | Indication |
|---|---|---|
| Fast Track | USA | Autoimmune haemolytic anaemia |
Orphan Status
| Indication | Patient Segment | Country | Organisation | Event Date |
|---|---|---|---|---|
| Autoimmune haemolytic anaemia | - | USA | Rigel Pharmaceuticals | 31 Jan 2018 |
| Idiopathic thrombocytopenic purpura | - | Japan | Kissei Pharmaceutical | 29 Feb 2020 |
| Idiopathic thrombocytopenic purpura | - | South Korea | Kissei Pharmaceutical | 07 Apr 2023 |
| Idiopathic thrombocytopenic purpura | - | USA | Rigel Pharmaceuticals | 08 Sep 2015 |
Commercial Information
Involved Organisations
| Organisation | Involvement | Countries |
|---|---|---|
| Rigel Pharmaceuticals | Originator | USA |
| Rigel Pharmaceuticals | Owner | USA |
| Knight Therapeutics | Market Licensee | Latin America |
| Kissei Pharmaceutical | Licensee | China, Japan, South Korea, Taiwan |
| Grifols | Licensee | Europe, Turkey |
| Medison Pharma | Licensee | Canada, Israel |
| Inmagene | Sub-licensee | China, Hong Kong, Macau |
| JW Pharmaceutical | Sub-licensee | South Korea |
| United States Department of Defense | Funder | USA |
| Inova | Collaborator | USA |
| Duke University Medical Center | Collaborator | USA |
| National Heart, Lung and Blood Institute | Collaborator | USA |
| Imperial College of Science, Technology and Medicine | Collaborator | United-Kingdom |
| Vanderbilt University Medical Center | Collaborator | USA |
| Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Collaborator | USA |
Brand Names
| Brand Name | Organisations | Indications | Countries |
|---|---|---|---|
| TAVALISSE | Rigel Pharmaceuticals | Idiopathic thrombocytopenic purpura | Israel |
| TAVLESSE | Grifols | Idiopathic thrombocytopenic purpura | Europe |
| Tavalisse | Rigel Pharmaceuticals, Kissei Pharmaceutical | Idiopathic thrombocytopenic purpura | Canada, Japan, USA |
Credit Suisse Market Status
| Indication | Region | Company | Phase | Expected Launch Year | Probability of Success% | Patent Expiry Year | Expected Generic Entry | Last Update |
|---|---|---|---|---|---|---|---|---|
| Cancer | Wrld (50% US) | - | Development Stopped | - | - | - | - | 05 Nov 2023 |
| ITP | ex US | Grifols | Marketed | 2020 | 100 | - | - | 05 Nov 2023 |
| Rheumatoid arthritis | Wrld (50% US) | - | Development Stopped | - | - | - | - | 05 Nov 2023 |
Credit Suisse Financial Forecast
| Indication | Region | 2021 | 2022 | 2023 | 2024 | 2025 | 2026 | 2027 | 2028 | 2029 | 2030 | Last Update |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ITP | ex US | 15 | 20 | 35 | 45 | 54 | 65 | 76 | 88 | 95 | 100 | 05 Nov 2023 |
| Total | 15 | 20 | 35 | 45 | 54 | 65 | 76 | 88 | 95 | 100 |
Scientific Summary
-
Adverse Events
Frequent:
Diarrhoea
Occasional: Dizziness; Elevated liver enzymes; Febrile neutropenia; Fever; Headache; Hypertension; Mucositis; Nasopharyngitis; Nausea; Neutropenia; Vomiting
Pharmacokinetic Measures
| Characterstic | Measure |
|---|---|
| Active Metabolites | yes |
Adverse Events
B-cell lymphoma
In a phase II trial involving 68 patients with relapsed or refractory B-cell lymphoma, the most common treatment-related adverse events included cytopenias, fatigue, diarrhoea/abdominal discomfort, and hypertension; all of which were mild to moderate and reversible. There were four cases of febrile neutropenia and eight patients required dose-modification due to neutropenia, hypertension, liver function test abnormalities, fever, and mucositis [183] [182] [147] .
Rheumatoid arthritis
Phase III
in the phase III OSKIRA-1 trial in patients with rheumatoid arthritis (RA), the most common adverse events were diarrhoea, headache, hypertension, nausea and nasopharyngitis. The randomised, placebo-controlled trial enrolled 923 patients with rheumatoid arthritis who had an inadequate response to methotrexate. The trial evaluated safety and tolerability of two dosing regimens of fostamatinib, specifically, 100mg twice daily or 100mg twice daily for four weeks followed by 150mg once daily [126] .
Further data from the pivotal OSKIRA-2 and OSKIRA-3 trials have confirmed that fostamatinib continues to be well tolerated in patients with RA who have had an inadequate response to DMARDs. The OSKIRA (Oral SYK Inhibition in Rheumatoid Arthritis) programme was designed to assess fostamatinib as a potential new oral treatment option for RA and an alternative to injectable therapies in patients with an inadequate response to conventional DMARDs, including methotrexate (OSKIRA-1 and OSKIRA-2) and those with an inadequate response to TNF-α antagonists (OSKIRA-3). The safety findings in both the OSKIRA-2 and OSKIRA-3 studies were generally consistent with those observed in the prior OSKIRA-1 study, as well as the phase II TASKI trials for RA [8] .
Phase II:
in a phase II TASKI-1 trial involving 189 patients with active RA who were treated with fostamatinib (50mg, 100mg and 150mg twice daily), the major adverse events were dose-related and reversible, including diarrhoea (45% with the 150mg bid dose) and neutropenia (occurred in overall of 15% of patients treated with fostamatinib. In this 3-month trial, 189 patients with RA who were receiving chronic methotrexate therapy were randomised to receive fostamatinib 50mg bid (n = 46), 100mg bid (n = 49), 150mg bid (n = 47), or placebo (n = 47). Other adverse events included dizziness (11% of fostamatinib 150mg bid recipients vs 2% of placebo recipients) and high BP (5% of patients in the higher fostamatinib dose groups vs 0% in the placebo group). Six patients treated with fostamatinib 50mg bid, 6 patients receiving fostamatinib 100mg bid, 8 patients treated with fostamatinib 150mg bid , and 11 patients treated with placebo discontinued the study because of consent withdrawal or adverse events. Neutropenia, requiring dose reduction, occurred in 5 patients and 10 patients treated with fostamatinib 100 and 150mg, respectively. Three patients receiving the highest dose of fostamatinib had ALT levels >3XULN. There was also a significant decrease from baseline in the biomarkers serum IL-6 and MMP-3 levels in the fostamatinib 100mg and 150mg bid dose groups, versus the placebo group, as early as week 1 and also at week 12. Moderate-to-severe diarrhoea occurred in 3 patients, 2 patients and 10 patients treated with fostamatinib 50mg, 100mg and 150mg bid, respectively. Upper gastrointestinal adverse events (gastritis, nausea, dyspepsia) occurred in one patient, two patients and 12 patients receiving fostamatinib 50mg, 100mg and 150mg bid, respectively, compared with two patients receiving placebo. 158 of the 189 patients (84%) completed the study, including 122 patients (86%) in the fostamatinib groups and 36 patients (77%) in the placebo group [140] [184] .
In a phase II trial of fostamatinib in patients with chronic refractory immune thrombocytopenic purpura, the primary adverse events were gastrointestinal. Treatment elevated blood pressure in some patients but did not appear to significantly effect neutrophil counts [185] [186] .
Immune thrombocytopenic purpura (ITP)
Phase III
Mild or moderate adverse events (AEs), with gastrointestinal related AEs were observed most frequently, and were reversible over time. No new or unusual safety issues were reported in the randomised, double-blind, phase III FIT 1 and FIT 2 trials evaluating fostamatinib versus placebo in patients with persistent or chronic ITP [52] [46] [50] [51] [56] .
Results from a phase III trial in patients with idiopathic thrombocytopenic purpura, safety of fostamatinib was observed in Japanese patients with primary ITP, along with the feasibility of glucocorticoid reduction/discontinuation during fostamatinib treatment, and a lack of bleeding events after abrupt discontinuation of fostamatinib. Adverse events were reported in 96% (21/22) of the fostamatinib-fostamatinib group and 100% (11/11) of the placebo-fostamatinib group, and treatment related adverse events in 77% (17/22) and 46% (5/11), respectively. In the washout period, adverse events were reported in 50% (6/12) of patients, and treatment related adverse events in 0% (0/12). We found no new safety risk or late-onset adverse events specific to Japanese patients [38] [37] [36] .
Autoimmune haemolytic anaemia:
Phase III: Results from a phase III FORWARD trial demonstrated that fostamatinib was generally safe and well-tolerated. The most common adverse events (≥10%) with fostamatinib and placebo were diarrhea (26.7% and 6.7%), hypertension (24.4% and 17.8%), fatigue (15.6% and 11.1%), pyrexia (13.3% and 6.7%), nausea (13.3% and 8.9%), and dyspnea (13.3% and 11.1%). There were five deaths on the study (2 with fostamatinib and 3 with placebo), all of which were determined to be unrelated to study drug [71] [70] [61] .
Data from two patients with relapsed/refractory diffuse large B-cell lymphoma who have had therapeutic benefits for over six years in a phase II study demonstrated an event of ventricular fibrillation and grade 4 cardiac arrest at Day 90 in one of them. The event was treatment unrelated and resolved [176] [148] .
In the FIT phase III long-term extension study 049, AEs were reported by 95 (77%) patients and were mild/moderate in 92 (75%). The most common AEs were diarrhea and hypertension, which were manageable with targeted treatment, fostamatinib dose modifications, or treatment withdrawal (5 patients withdrew due to diarrhea and none due to hypertension). Serious adverse events (SAE) were reported in 28 patients (23%), were considered unrelated to fostamatinib in 23 patients (19%) and included bleeding-related SAEs in 11 subjects (9%), thrombocytopenia in 6 subjects (5%), epistaxis in 3 (2%), sepsis in 2 (2%) and transaminases increased in 2 (2%). Adverse events were consistent with those reported during the placebo-controlled trials [55] [56]
The most common clinically meaningful drug-related adverse events noted in the 6-month, randomised, phase IIb TASKi-2 trial of fostamatinib were diarrhoea and hypertension. With dose reductions (which were pre-specified in the trial protocol), patients generally completed the trial with minimal safety issues. The most common adverse events in the trial overall were related to infections, and these were generally evenly distributed among the active treatment and placebo groups. In the placebo, 150mg QID and 100mg bid groups, the percentages of patients experiencing diarrhoea were 3%, 12% and 19%, and the percentages experiencing hypertension were 5%, 12% and 14%, respectively. The percentages experiencing infections were 27%, 24% and 35%, respectively. Other adverse events included, nausea, vomiting, dizziness and elevated liver enzymes. The mean increase in blood pressure from baseline, at 6 months (using LOCF methodology) was< 0.5 mmHg for the 150mg od group, and ~1mmHg for the 100mg bid group. Approximately 18% and 23% of patients in the 150mg od and 100mg bid groups, respectively, had blood pressure medication adjusted (or in some cases initiated) during the trial, compared with 7% of the placebo patients. The trial enrolled 457 patients with rheumatoid arthritis, all of whom received stable doses of methotrexate throughout the study period [133] .
The most common clinically meaningful drug-related adverse events noted in the 3-month, phase IIb TASKi-3 trial were diarrhoea and hypertension. In the placebo and fostamatinib groups, 3% and 14% of patients, respectively, opted for pre-specified dose reductions, which generally allowed them to complete the trial safely. Diarrhoea occurred in 7% and 12%, and hypertension occurred in 4% and 13% of placebo- and fostamatinib-treated patients, respectively. Grouped together, diarrhoea, nausea, vomiting or dizziness occurred in 1% and 5% of placebo and fostamatinib patients, respectively. The most common adverse events in the trial overall were related to infections, though these were evenly distributed among the placebo and fostamatinib groups: 21% and 23%, respectively. Neutropenia (ANC <1500) occurred in 2% of fostamatinib patients, but not in placebo patients, and liver enzyme elevations occurred in 3% of fostamatinib patients, but not in placebo patients. Increased blood pressure occurred in 1% and 5% of placebo and fostamatinib patients, respectively. The mean increase in blood pressure at 3 months, from baseline, using LOCF methodology, was +3.6/+3.2 mmHg in the fostamatinib group. Approximately 17% of patients in that group had blood pressure medication adjusted, or in some cases initiated, during the trial, compared with 8% of placebo patients. For those who had blood pressure medications adjusted or initiated, their blood pressure was successfully reduced, and was generally well-controlled throughout the trial. The trial enrolled patients with rheumatoid arthritis who had failed at least one marketed biologic agent, including anti-TNF injectables. Patients were randomised to fostamatinib 100mg bid (n = 146) or placebo (n = 73). All patients were on stable doses of methotrexate throughout the trial [136] .
Updated data from a phase II trial of fostamatinib in adults with warm antibody autoimmune hemolytic anemia (wAIHA) who had failed at least one prior treatment, the most commonly reported adverse events (AEs) were diarrhea (42%), fatigue (42%), hypertension (27%), dizziness (27%), and insomnia (23%). The reported AEs were manageable and consistent with the fostamatinib safety database of over 3,900 patients across multiple diseases (rheumatoid arthritis, B-cell lymphoma, COVID-19, and immune thrombocytopenia (ITP)). No new safety signals were detected [88] . Earlier the safety data from the phase II SOAR trial demonstrated that the overall, adverse events (AE) were manageable and consistent with those previously reported with fostamatinib in other conditions. No new safety signals were detected. The most common AEs during the initial treatment period were diarrhoea in 9, fatigue in 8, hypertension in 7, and dizziness in 6 patients. Seven patients had serious AEs, including anemia, acute myocardial infarction, fall, Hgb decreased, inappropriate secretion of antidiuretic hormone, infection, pneumonia, rhabdomyolysis, sepsis, skin necrosis, and systemic inflammatory response syndrome. Two patients had AEs leading to death: one had infection with skin necrosis and calciphylaxis; the other had pneumonia. Neither were considered related to treatment, and both patients were immunosuppressed due to steroids. Six patients (24%) received rescue therapy, including RBC transfusion, prednisone and/or immunoglobulins. In the trial, 6 patients discontinued the study, including 3 who withdrew, 1 was lost to follow up, and 2 had a loss of response (1 of whom also had increased alanine aminotransferase) from nine patients who entered the extension phase [87] . Nine patients had more than one AE, six patients had treatment-related AEs. AEs were mostly mild to moderate, and the most common AEs were upper respiratory tract infection. Three grade 3 AEs were reported in two patients. AEs resulted in dose reduction in two patients, dose interruption in two, and study drug withdrawn in one. One patient had a serious AE (inappropriate antidiuretic hormone secretion), which was not related to fostamatinib andno new safety signals were reported. Results from the phase II SOAR trial for fostamatinib showed that of 17 patients enrolled two patients withdrew early from the study due to non-safety-related reasons and will be replaced per the study protocol. The drug was safe and well tolerated. Two patients died during the trial due to non-treatment related serious adverse events. One patient who showed non-treatment related serious adverse events was recovered [85] [189] [75] [76] [74] [86] .
COVID-2019 infections:
Phase II:
In a phase II trial in patients with COVID-2019 infections, administration of fostamatinib did not increase the incidence of serious adverse events (SAEs) compared with placebo. The overall incidence of SAEs by Day 29 was approximately 50% less in the fostamatinib group (10.5%) compared with the placebo group (22.0%) (p=0.2) . The most frequent SAE reported by Day 29 was hypoxia, occurring in 1 patient receiving fostamatinib and 3 patients receiving placebo [106] . Earlier, positive top-line results from the trial demonstrated significant safety profile. At Day 29, in the overall population zero deaths were reported in the fostamatinib group of thirty patients compared to three deaths in the placebo group of twenty-nine patients (p=0.07). In more severe patients, with an ordinal scale assessment of 6 or 7, the difference was zero of nineteen patients compared to three of seventeen patients (p=0.049), respectively [102] [105] .
Phase III
The updated results from phase III FOCUS trial demonstrated that Treatment-emergent adverse events were consistent with previous studies and were similar between the 2 groups [100] . In data from phase III trial in hospitalised COVID-19 patients without respiratory failure, fostamatinib treatment resulted in 8 adverse events (AEs) in five patients. One AE was serious and was resolving. No deaths were reported. The safety profile for fostamatinib was consistent with prior clinical experience and no new safety issues were discovered. The safety profile between fostamatinib and placebo was generally comparable [99] [96] [95] .
Phase I
all doses of R 406 (80-600mg), the metabolite of fostamatinib, were well tolerated up to the 200mg dose level among healthy volunteers in a randomised, double-blind, controlled phase I trial (n = 35). The 600mg dose was associated with increased frequency of postural dizziness [187] [190] .
Fostamatinib did not adversely affect QT/QTc intervals in a double-blind, double-dummy controlled trial in 208 healthy volunteers. Subjects were randomised to a standard dose of fostamatinib 100mg bid or 300mg bid, moxifloxacin, or placebo, dosed for 4 days. Fostamatinib (both doses) did not induce significant QT/QTc elevations, whereas moxifloxacin did induce elevations [137] .
IgA Nephropathy
Phase II: Topline data from the phase II trial demonstrated that fostamatinib was well tolerated with mostly mild to moderate adverse events. The most frequent adverse events reported were headache, hypertension, diarrhoea, nausea and vomiting. Two patients from fostamatinib (100mg) group and four patients from fostamatinib (150mg) group discontinued the trial due to adverse events. Serious adverse events were reported by six patients, two each from the placebo group and both fostamatinib dose groups. A drug related serious adverse event was observed in one patient from each of the fostamatinib groups and a fatal serious adverse events not related to treatment was observed in one patient. The randomised, double-blind, ascending-dose, placebo controlled, proof-of-concept trial enrolled 76 patients with IgA nephropathy [113] [117] .
Ovarian cancer
phase I:
The adverse events data from phase I trial in ovarian cancer showed that fostamatinib (Fos) in combination with paclitaxel (wPac) was well tolerated. The most common AEs associated with either Fos and wPac or both were diarrhea (70%), fatigue (52%), anemia (44%), neutropenia (33%), nausea (33%), hypertension (30%), and dysgeusia (30%). The treatment emergent AEs with grade 3/4 were found to be neutropenia (37%), anemia (26%), and thromboembolic event (22%). Among 10 evaluable patients, no dose limiting toxicities were observed in all the three dose levels. Out of 15 patients in dose expansion cohort, one DLT (neutropenia) was observed in one patient and one patient was infected with grade 5 infection [110] [111]
Pharmacodynamics
Summary
In syk-transformed pre-B cells, treatment with R 406 allowed the cells to differentiate normally; without treatment, the cells transformed to result in leukaemia in the animal model [151] .
Results from in vitro and in vivo studies have shown that addition of fostamatinib to several drugs (including fludarabine and rapamycin) appeared to increase activity against non-Hodgkin's lymphoma (NHL). First, using a human diffuse large B cell lymphoma (DLBCL) cell line of GCB genotype (OCI-Ly19), the in vitro effects of combining of R 406 with fludarabine, rapamycin, rituximab, bendamustine and bortezomib were analysed. Increased cytotoxicity was observed using in vitro culture assays with the addition of fludarabine, rapamycin, or rituximab to R 406. Cell viability at 72 hours was 25% with R 406 alone, 27% for fludarabine alone, and only 9% for the fludarabine + R406. At 48 hours, cell viability was 49% using R 406 alone, 31% using rituximab alone, and 21% for rituximab + R 406. At 120 hours using primary lymphoma cells (DLCL27), there were no viable cells treated with the rapamycin + fostamatinib combination, compared with rapamycin alone (7%) or fostamatinib alone (25%). The addition of bortezomib or bendamustine to fostamatinib resulted in only a minimal additive increase in cytotoxicity. In mice with DLBCL cell line OCI-Ly19 tumours, animals were simultaneously treated with fostamatinib (n = 7; 3 mg/kg ad. lib.; translated into 2-5 micromolar R 406 systemically throughout the 24-hour period) and either bortezomib, (n = 6; 0.4 mg/kg weekly IP), or rituximab, (n = 13; 3 mg/kg, twice weekly IP). Analysis of the OCI-Ly19 tumour volumes at day 46 showed a median of 2364 mm3 with bortezomib alone, compared with 1823 mm3 with bortezomib + fostamatinib. The most significant cytotoxicity was observed with fostamatinib + rituximab (median tumour volume of 497 mm3 ; p = 0.01), versus fostamatinib alone (3150 mm3) or rituximab alone (1764 mm3) [179] .
In vitro
cell based assays evaluating fostamatinib in Waldenström's macroglobulinemia (WM) revealed that spleen tyrosine kinase (SYK) was involved in B-cell antigen receptor (BCR) mediated signaling and cell adhesion in WM. Anti-IgM or PMA alone stimulated the adhesion of MWCL-1 on fibronectin. The addition of R 406 (the active metabolite of fostamatinib) had a comparable effect to ibrutinib on inhibition of IgM mediated cell adhesion (IC50 = 0.32µM), consistent with the effect of both compounds on BCR mediated signaling. Neither compound affected PMA induced cell adhesion, indicating that the effect on IgM mediated cell adhesion was not due to toxicity. Lack of off-target toxicity was further confirmed in the MWCL-1 proliferation assays where the compounds showed less potency than in BCR-mediated assays. Comparable inhibition of adhesion and proliferation was seen with CAL 101 [112] .
Fostamatinib delayed disease progression and prolonged survival in a murine model of lupus. The study evaluated the effects of three doses of fostamatinib versus a control group and an untreated group of lupus-prone mice. The mice in the R 788 groups received 10 mg/kg, 20 mg/kg or 40 mg/kg, PO, twice a day, for 240 days. On completion of dosing, 2/29 mice in the 40 mg/kg group had elevated proteinuria compared to 21/30 mice in the control group. All 29 of the mice treated with 40 mg/kg of fostamatinib survived the duration of the study, compared to 14/30 mice in the control group. In a separate study, where treatment was initiated after the onset of disease, approximately 95% of the animals given the 40 mg/kg dose had elevated proteinuria levels that decreased following the onset drug treatment [155] .
In vivo
, twice daily administration of R 406 30 mg/kg po prevented the ES50 value reduction in response to electrial field stimulation of tracheal smooth muscle rings observed in ovalbumin-exposed and vehicle-treated BALB/c mice. In this mast cell dependent model of allergen-induced airway hyperresponsiveness and airway inflammation, R 406 also inhibited mast cell degranulation and cytokine production induced by cross-linking FcεRI. In a mast cell independent model R 406 significantly inhibited allergen-induced airway hyperresponsiveness and accumulation of eosinophils. R 406 also prevented increases in IL-13 levels in the bronchoalveolar lavage fluid of sensitised and challenged mice in this model [188] .
R 406, the metabolite of fostamatinib, dose-dependently inhibited human basophil CD63 expression after ex vivo anti-IgE stimulation of whole blood basophils collected from healthy volunteers dosed at 80-600mg in a randomised, double-blind, controlled trial (n = 35). Single doses of the drug at ≥ 250mg (>90% inihibition at 2-6h post-dose) resulted in prolonged inhibition of Fcε receptor (FcεR) activation with suggested EC50 values in the range of 1 µmol/L (5-600 ng/mL). Researchers concluded that R 406 could potentially have similar effects on Fcγ receptor (FcγR) signalling that could be used for treatment of arthritis as well as other inflammatory conditions [187] .
Therapeutic Trials
Ovarian cancer
phase I:-
The efficacy data from phase I trial showed that out of 18 evaluable patient treated with dose level 3, 7 (39%) had partial or complete response (95% CI: 17.3, 64.3%) [110] [111]
Results from a phase II clinical trial in patients with relapsed or refractory B-cell lymphoma showed that in 23 patients with diffuse large B-cell lymphoma, 5 patients showed an overall response. Out of 21 patients with follicular lymphoma, two showed an overall response. Among 11 patients with chronic lymphocytic leukaemia or small cell lymphocytic leukaemia, six experienced an overall response, and in nine patients with mantle cell lymphoma, one showed an overall response. Stable disease was seen in an additional 23 patients, including follicular lymphoma (12), diffuse large B-cell lymphoma (4), mantle cell lymphoma (4), and chronic lymphocytic leukemia/small lymphocytic lymphoma (2), and MALT lymphoma (1) [183] [182] [147] .
In a phase II study in patients with relapsed/refractory diffuse large B-cell lymphoma, one patient each had a complete and a partial response, while seven patients had stable disease. Data from two patients with therapeutic benefits for over six years demonstrated maintenance of complete response for over 5 years in one patient. The other patient has had a partial response with sustained improved metabolic response for over six years [176] [148] .
IgA Nephropathy:
Phase II
Topline data from the proof of concept phase II trial in patients with IgA nephropathy indicated that the trial failed to attain statistical significance for its primary endpoint. The mean change in proteinuria was -177, -577 and -158 mg/g for the placebo and fostamatinib (100mg and 150mg twice daily) dose groups respectively at 24 weeks. Analysis of initial data from a pre-specified sub-group of patients (proteinuria > 1 gm/day at baseline) demonstrated a greater, dose-dependent reduction in proteinuria for fostamatinib treated patients relative to placebo patients. The mean change in proteinuria, in patients with baseline proteinuria > 1 gm/day, was -177, -720 and -803 mg/g for the placebo and fostamatinib (100mg and 150mg twice daily) dose groups respectively at 24 weeks. A similar dose dependent reduction in proteinuria for fostamatinib treated patients relative to placebo patients was observed in patients with baseline proteinuria > 2 gm/day. The randomised, double-blind, ascending-dose, placebo controlled, proof-of-concept trial enrolled 76 patients with IgA nephropathy [113] [117] .
Autoimmune haemolytic anaemia:
Phase III: Updated results from phase-III FORWARD trial demonstrated the primary endpoint of durable hemoglobin (Hgb) response rate was met by 15 (33.3%) patients in fostamatinib group compared to 6 (14.0%) patients who received placebo (p<0.0395). All 6 placebo responders were from Eastern Europe, and a regional analysis was conducted. The durable Hgb response rate with fostamatinib in the US, Canada, Australia, and Western Europe was significantly greater than with placebo (8/25 [32.0%] vs. 0/28, p=0.0021). The Hgb response rate with fostamatinib in Eastern Europe was not significantly different than placebo (7/20 [34.0%] vs 6/15 [40%]). The study randomised 90 patients to fostamatinib (n=45) or placebo (n=45) with patient median age 58 and 64 years [71] . Results from a phase III FORWARD trial demonstrated that Durable hemoglobin response rate was 16 (35.6%) in the treatment group (n=45) and 12 (26.7%) in the placebo group (n=45) (p=0.398). Durable hemoglobin response rate in Eastern Europe was 7 (35.0%) in the treatment group (n=20) and 9 (52.9%) in the placebo group (n=17) (p=0.304). Number of subjects with haemoglobin response on at least one visit was 21 (46.7%) in the treatment group (n=45) and 16 (35.6%) in the placebo group (n=45). Number of subjects with haemoglobin response on at least one visit in Eastern Europe was 8 (40.0%) in the treatment group (n=20) and 11 (64.7%) in the placebo group (n=17). Number of subjects with change in Hgb from baseline of ≥2 g/dL was 22 (48.9%) in the treatment group (n=45) and 16 (35.6%) in the placebo group (n=45). Number of subjects with change in Hgb from baseline of ≥2 g/dL in Eastern Europe was 22 (48.9%) in the treatment group (n=45) and 16 (35.6%) in the placebo group (n=45). Change in mean Hgb from baseline to end of treatment LS Mean (95% CI) was 1.8 (1.06, 2.54) in the treatment group (n=45) and 1.85 (1.07, 2.63) in the placebo group (n=45). Change in mean Hgb from baseline to end of treatment LS Mean (95% CI) in Eastern Europe was 1.28 (-0.07, 2.64) in the treatment group (n=45) and 2.27 (0.88, 3.66) in the placebo group (n=45). Number of subjects free (no use) of rescue therapy after week 4 was 18 (40.0%) in the treatment group (n=45) and 18 (40.0%) in the placebo group (n=45). Number of subjects free (no use) of rescue therapy after week 4 in Eastern Europe was 6 (30.0%) in the treatment group (n=45) and 10 (58.8%) in the placebo group (n=45). Change from baseline to week 24 in Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT-F) scale LS Mean (95% CI) was 2.9 (-0.70, 6.50) in the treatment group (n=45) and 1.9 (-1.85, 5.69) in the placebo group (n=45). Change from baseline to week 24 in Functional FACIT-F scale LS Mean (95% CI) in Eastern Europe was -0.7 (-6.28, 4.86) in the treatment group (n=45) and 4.7 (-1.33, 10.73) in the placebo group (n=45) [70] [61] .
In a phase II trial, fostamatinib improved platelet counts in patients with chronic refractory immune thrombocytopenic purpura (ITP). Overall, these patients were highly refractory with most having failed several other therapies. A total of 10 patients had failed splenectomy and 5 were over 70 years old. From the first 14 patients studied, 64% responded favourably to treatment and demonstrated higher stable platelet counts. Six of these patients had peak platelet counts of greater than 100 000 platelets/µL of blood. Two patients who were previously receiving weekly intravenous gammaglobulin maintained platelet counts while on only fostamatinib for 20 weeks. For these two patients, this marked the first time in 10 years that each achieved prolonged avoidance of intravenous immunoglobulin G (IgG) injections. Various doses of fostamatinib were evaulated in this study with most patients receiving between 100 and 175 mg/day, administered twice-daily [185] [186] .
Phase III
Fostamatinib achieved a stable platelet response in the 18% of patients (n=76) with chronic immune thrombocytopenia (ITP) when compared with placebo (p=0.0261). The patients observed an increased platelet count at week 24, a median of more than 100,000/µL from a baseline median of 16,000/uL. The double-blind, phase III, first FIT 1 trial, which randomised patients in a 2:1 ratio to receive either fostamatinib or placebo [46] [51] . In the phase III FIT 2 study, the fostamatinib response rate was 18%, consistent with the phase III FIT 1 study. A stable platelet response was achieved in only one patient in the placebo group (4%) and therefore the difference between those on treatment and those on placebo did not reach statistical significance (p = 0.152). The combined dataset reveals this difference to be statistically significant (p = 0.007), including the increase in platelet count from a median of 18 500/µL of blood at baseline to more than 100 000/µL at week 24 of treatment in patients who met the primary endpoints. The consistent efficacy of fostamatinib across various clinical and treatment backgrounds was demonstrated by a statistically superior stable platelet response in the fostamatinib group versus the placebo group in all subgroup analyses: prior splenectomy or not; prior exposure to TPO agents or not; platelet counts below or above 15,000/µL of blood at baseline [52] .
Results from a phase III trial in patients with idiopathic thrombocytopenic purpura demonstrated that the patients treated with fostamatinib achieved long term efficacy, stable platelet response significantly higher than patients receiving a placebo control, which is defined as greater than or equal to 50,000 platelets per µL of blood on at least four of the last six scheduled visits between weeks 14 and 24 of treatment. The platelet response rate was 36% (8/22) in the fostamatinib-fostamatinib group and 27% (3/11) in the placebo-fostamatinib group. The platelet count of the responders in the fostamatinib-fostamatinib group increased to ≥50×103/μL shortly after initiating fostamatinib and remained around 100×103/μL between Week 14 and Week 52, whereas the platelet count of the responders in the placebo-fostamatinib group remained low while receiving placebo but increased after receiving fostamatinib. Among 14 patients with concomitant glucocorticoids treatments at the beginning of the open label period, 43% (6/14) reduced or discontinued glucocorticoids while receiving fostamatinib without disease relapse. In the washout period of up to 4 weeks, all 12 patients experienced a mild decrease in platelet count, but none developed bleeding events. Three of four patients who completed the 4-week washout period had a slight increase in platelet counts from Week 2 to Week 4 [38] [37] [36] .
Updated results from the open-label extension demonstrated that 56% of subjects with a stable response maintained the response for ≥24 months. Of 27 patients with a stable response, 21 (78%) maintained the response at Month 12 of fostamatinib treatment, and 15 (56%) at Month 24. At Month 12, median platelet count for the 49 subjects was 72,000/µL (range: 9000-333,000 µL). For the 32 subjects at Month 24, median platelet count was 80,500/µL (range: 7000-315,000/µL). An overall platelet response was achieved by 57/123 (46%) patients. In the FIT phase III long-term extension study 049, 118 patients who responded to fostamatinib in the parent studies (047 and 048) and exposed to fostamatinib for a median of 13 months through the combined parent and 049 trials had a median platelet count of 96 000/µL of blood.In addition, 41 out of 44 former placebo patients from the 047 and 048 studies that enrolled in the 049 study, 22% (n = 9/41, p = 0.0078) achieved a prospectively defined stable platelet response [55] [44] [45] [52] [56] .
In the pooled analysis from the phase III 047 and 048 studies, stable response was reported in 18 and transient response was reported in 11 of the 101 treated patients, compared with only one stable response and no transient responses in patients receiving placebo (n = 49). The overall response rate was 29% (29/101) in fostamatinib arm and 2% (1/49) in placebo arm (p = < 0.0001) [45] [50] [51] .
Data from the FIT phase III trials (047, 048 and 049 studies) demonstrated that fostamatinib was effective for certain immune thrombocytopenic purpura patients. Additionally, the benefit was consistent across all sub-groups analysed including TPO (blood platelet production booster) experienced patients who had limited treatment options remaining [44] [50] [51] [56] .
In patients with idiopathic thrombocytopenic purpura from phase III trials, a stable platelet response to fostamatinib was associated with presence of anti-platelet autoantibodies. Of 38 patients positive for autoantibodies, 13 (34%) had stable platelet responses. In 47 patients who were negative for autoantibodies, 6 (13%) had stable platelet responses. In the exploratory analysis, Plasma samles were collected from 85 patient, of whom 38 (45%) were positive for one or more anti-platelet autoantibodies and 19 (22%) were from patients with a stable platelet response to fostamatinib [177] .
Phase II:
Updated data from a phase II trial of fostamatinib in adults with warm antibody autoimmune hemolytic anemia (wAIHA) who had failed at least one prior treatment, demonstrated that fostamatinib rapidly and durably increased hemoglobin (Hgb) levels, with clinically meaningful Hgb responses observed in nearly half of the patients. The primary endpoint was Hgb greater than 10 g/dL with an increase of =2 g/dL from baseline by Week 24 without rescue therapy or red blood cell transfusion. The trial demonstrated that 46% (11/24) of patients achieved the primary endpoint, with 1 late responder at week 30 (total of 12 responders [50%]). Increases in median Hgb were detected at Week 2 and sustained over time [88] . Earlier the results from the phase II SOAR trial showed that primary efficacy endpoint of haemoglobin (Hgb) level >10 g/dL was met by 44% (11/25) patients with an increase of =2 g/dL from baseline by week 24. The overall response rate was found to be 48% (total of 12 responders) including one responder at week 30. Increase in the median Hgb were generally detected at week 2 and sustained over time, with 24% achieving the primary endpoint by week 2. Median Hgb of responders increased by >2.0 g/dL from baseline by week 4 versus no change for non-responders. Thirteen patients entered the extension period of the trial, including 9 of 11 responders, 1 late responder, seven patients were still on the treatment and 3 patients with a beneficial trend during the initial treatment phase. Five of nine patients had an ongoing response to fostamatinib and none had rescue therapy or an RBC transfusion. Updated data from stage 1 of the trial demonstrated an increased clinical response rate, whereby 53% (9/17) of evaluable patients achieved a response to fostamatinib treatment. Six patients responded during the 12-week evaluation period and an additional three patients met the response criteria in the extension study after 12 weeks of dosing. Interim results showed that out of 17 patients enrolled in stage 1, four responded and an additional two patients met the response criteria in the extension study after 12 weeks of dosing for a response rate of 35% (6/17) [84] [85] [76] [74] [86] [68] [72] [83] .
Phase III:
Top-line data from the pivotal phase III trials, OSKIRA-2 and OSKIRA-3, have demonstrated that fostamatinib in combination with disease modifying anti-rheumatic drugs (DMARDs) led to significant improvements in ACR20 response rates in selected dose cohorts of patients with RA who have had an inadequate response to DMARDs. In the OSKIRA-2 study, fostamatinib in combination with DMARDs significantly improved ACR20 response rates at 24 weeks in the fostamatinib 100mg twice daily (BID) group and the group receiving fostamatinib 100mg BID for 4 weeks followed by 150mg once daily (QD), compared with placebo (39.6% and 39.6% vs 24.5%). In the OSKIRA-3 study involving RA patients inadequately responding to methotrexate (MTX) and a single TNF-alpha antagonist, fostamatinib in combination with MTX led to significant improvements in ACR20 response rates at 24 weeks in the fostamatinib 100mg BID group (36.2%; p = 0.004 vs placebo), but not in the 100mg BID/150mg QD group (27.8%) or the placebo group (21.1%) [8] .
Primary endpoint analysis of the phase III OSKIRA-1 trial demonstrated that treatment with fostamatinib significantly improved the ACR20 response rate, compared with placebo, in patients with rheumatoid arthritis who had an inadequate response to methotrexate. In this double-blind study, 923 patients were randomised to receive either fostamatinib 100mg twice daily or fostamatinib 100mg twice daily for 4 weeks then 150mg once daily, or placebo. The respective ACR20 response rates at 24 weeks were 49% and 44% versus 34% (both p < 0.01). However, for the other primary endpoint, the modified Total Sharp Score (mTSS), no significant difference was observed at 24 weeks in either of the fostamatinib groups, compared with placebo [126] .
Phase II:
In the phase IIb OSKIRA-4 study, fostamatinib was superior to placebo at 6 weeks in change from baseline in DAS28 score in 280 DMARD-naïve patients with active RA. The 6-month trial compared three dose regimens of fostamatinib (100mg twice daily, 100mg twice daily for a month followed by 150mg once daily, and 100mg twice daily for a month followed by 100mg once daily) with adalimumab monotherapy and placebo (NCT01264770). However, all dose regimens did not demonstrate non-inferiority against adalimumab monotherapy at 24 weeks (second primary objective) [125] .
Fostamatinib showed promise as a treatment for patients with active rheumatoid arthritis (RA) who were receiving methotrexate therapy in a double-blind, placebo-controlled, multicentre, phase IIa trial (TASKi-1). In this 3-month trial, 189 such patients were randomised to receive twice-daily fostamatinib 50mg (n = 46), 100mg (n = 49), 150mg (n = 47), or placebo (n = 47). The primary endpoint was the ACR 20 response at week 12; this endpoint was achieved by 32% of fostamatinib 50mg bid recipients, 65% of fostamatinib 100mg bid recipients, 72% of fostamatinib 150mg bid recipients, and 38% of placebo recipients. At week 12, significantly greater proportions of patients treated with fostamatinib 100mg bid and 150mg bid achieved ACR 20 (as above), ACR 50 and ACR 70, compared with patients treated with placebo or fostamatinib 50mg bid. An ACR 50 response at week 12 was achieved by 49% of fostamatinib 100mg bid recipients and 57% of fostamatinib 150mg bid recipients, compared with 17% of fostamatinib 50mg bid recipients and 19% of placebo recipients. A corresponding ACR 70 response was achieved by 33% of fostamatinib 100mg bid recipients and 40% of fostamatinib 150mg bid recipients, compared with 2% of fostamatinib 50mg bid recipients and 4% of placebo recipients. One hundred and fifty-eight of the 189 patients (84%) completed the study, including 122 patients (86%) in the fostamatinib groups and 36 patients (77%) in the placebo group [140] [184] .
Positive results demonstrated that fostamatinib, 100mg twice-daily or 150mg once-daily, significantly improved clinical response rates for up to six months in the phase IIb TASKi-2 trial in 457 patients with rheumatoid arthritis who not responded to prior methotrexate therapy. Patients were randomised to receive fostamatinib 100mg bid or 150mg od, or placebo. In addition, all patients received a stable dose of methotrexate throughout the trial. At 6 months, the active treatment groups had higher ACR 20, ACR 50, ACR 70 and DAS28 response rates than the placebo group. The onset of effect of fostamatinib occurred within a week after the initiation of therapy and was maintained. In the placebo group, the percentages of patients achieving ACR 20, ACR 50, ACR 70 and DAS28 <2.6, were 35%, 19%, 10% and 6%, respectively. In the 150mg od group, these values were 57% (p < 0.001 vs placebo), 32% (p = 0.007), 14% (p = 0.34) and 17% (p = 0.003), respectively. In the 100mg bid group, these values were 66% (p < 0.001 vs placebo), 43% (p < 0.001), 28% (p < 0.001) and 27% (p < 0.001). All patients received a stable dose of methotrexate throughout the trial [180] [133] .
The 3-month, phase IIb TASKi-3 trial in 219 patients with rheumatoid arthritis did not meet its efficacy endpoints; the fostamatinib-treated group (n = 146) did not report significantly higher response rates than the placebo group (n = 73) at 3 months. In the placebo group, the percentages of patients achieving ACR 20, ACR 50, ACR 70 and DAS28<2.6 were 37%, 12%, 6% and 10%, respectively. In the fostamatinib group, these values were 38% (p = 0.84 vs placebo), 22% (p = 0.09), 9% (p = 0.37) and 12% (p = 0.15), respectively. The ACR scores for the fostamatinib group were within the expected range, but the placebo response rates rose unaccountably between week 6 (at which point the reported response rates between fostamatinib and placebo were significantly different) and month 3. The objective components (C-reactive protein and erythrocyte sedimentation rate) of the ACR scores did show a significant difference between groups. Anatomical changes in the patients' wrist and hands were evaluated using MRI and scored using RAMRIS (Rheumatoid Arthritis Magnetic Resonance Imaging Scoring). These results showed improvements in the fostamatinib group vs placebo in the synovitis scores (-0.52 vs +0.35, respectively; p = 0.038) and the osteitis scores (-0.19 vs +1.17, respectively; p = 0.058), but no significant effect was seen in the erosion scores at 3 months (+0.78 vs +0.94, respectively; p = 0.62). Fostamatinib was dosed at 100mg bid and the trial enrolled patients who had failed at least one marketed biologic agent, including anti-TNF injectables. All patients were on stable doses of methotrexate throughout the trial [181] [136] .
COVID-2019 infections:
Phase III:
The updated results from the phase III FOCUS trial demonstrated that the primary endpoint was met; those who received fostamatinib had lower mean days on oxygen than those who received placebo (4.8 vs. 7.6 days, p=0.0136). Fostamatinib showed significance or trend towards significance in all secondary endpoints of reducing mortality and morbidity compared to placebo. The mean change in the 8-point ordinal score from baseline to the average of Day 5 to 15 was significantly improved in patients who received fostamatinib vs. placebo (p=0.0092). Furthermore, 6 patients were enrolled with baseline ordinal score of 6 (3 in each group). All patients in the fostamatinib group survived, and all in the placebo group died by Day 30. A significantly higher proportion of patients who received fostamatinib were discharged from the hospital by Day 15 compared to placebo (p=0.0029). Significantly more patients were alive and oxygen-free by Day 29 and Day 60 with fostamatinib treatment in comparison to placebo (p=0.0213 and p=0.0271, respectively) [100] . Results from the phase III FOCUS trial demonstrated that the trial did not meet statistical significance in the primary efficacy endpoint. The mean number of days on oxygen through Day 29 in the fostamatinib treatment arm was 6.9 days compared to 9.0 days in the placebo arm (p=0.0603). By Day 29, in the overall population, there were 4 deaths in the fostamatinib group compared to 8 in the placebo group. Fostamatinib numerically reduced patient all-cause mortality by 50% (p=0.4521). The mean change from baseline in clinical status score to Day 15 using the 8-point ordinal scale was -2.4 for fostamatinib and -1.9 for placebo (p=0.0428). The median number of days to first sustained hospital discharge by Day 29 was 6 days for fostamatinib and 7 days for placebo (p=0.2371). The proportion of patients alive and oxygen free on Day 29 was 85.1% for fostamatinib and 73.4% for placebo (p=0.0653). The number of days in the ICU was 2.2 for fostamatinib and 3.3 for placebo (p=0.1883). All prespecified secondary endpoints in the study numerically favored fostamatinib over placebo, including mortality, time to sustained recovery, change in ordinal scale assessment, and number of days in the ICU [99] [95] .
Phase II:
In a phase II trial treatment with fostamatinib was associated with clinically meaningful improvement in clinical outcomes in hospitalized COVID-19 patients who required supplemental oxygen. The median number of days on oxygen was 8 (IQR 5-10) in the fostamatinib group compared to 20 (IQR 14-27) in the placebo group (p=0.2). IQR demonstrate interquartile range which is the range of the first and third quartiles of the range as a measure of spread. The difference was even greater in more severe patients with the fostamatinib group at 10 days compared to placebo at 28 days (p=0.027). At Day 15, 65.5% of patients were free of supplemental oxygen in the fostamatinib group compared to 39.9% in the placebo group (p=0.08). In more severe patients, the difference was 57.9% compared to 20% (p=0.016). The median time to recovery was 8 days in both groups. The greatest benefits were observed in more severe patients where the median time to recovery was reduced from 13 days (IQR 11-19) in the placebo group to 10 days (IQR 6-13) in the fostamatinib group [106] . Earlier, positive top-line results from the trial demonstrated improvement in the disease conditions. Four intubated patients were involved in the trial on mechanical ventilation (ordinal scale 7) with two patients randomized to each treatment group. At Day 29, both patients in the fostamatinib group improved within 7 days and came off the ventilator, while both patients in the placebo group deceased. Fostamatinib was superior to placebo in accelerating improvement in clinical status by day 15 (mean change -3.6 compared to -2.6, p=0.035) and by day 29 (mean change -4.2 compared to -3.3, p=0.12) using ordinal scale assessments. The median number of days in the ICU was reduced by 4 days, from 7 days in the placebo group to 3 days in the fostamatinib group (p=0.07). Despite general SOC use of both steroids and remdesivir in all 59 patients, there was a consistently greater reduction in NETosis and other inflammatory biomarkers (CRP, Ferritin, D-Dimer, Fibrinogen) in the fostamatinib group as compared to the placebo group [102] [105] .
Future Events
| Expected Date | Event Type | Description | Updated |
|---|---|---|---|
| 31 Dec 2023 | Regulatory Status | Rigel Pharmaceuticals plans to launch Fostamatinib for Autoimmune haemolytic anaemia in 2023 (9351602) | 11 Mar 2022 |
| 31 Mar 2022 | Regulatory Status | Kissei Pharmaceuticals plans to submit a NDA with Pharmaceuticals and Medical Devices Agency (PMDA) for Idiopathic thrombocytopenic purpura in late 2021 or early 2022. [41] | 02 Jan 2023 |
| 31 Dec 2021 | Regulatory Status | Grifols plans to launch fostamatinib for Idiopathic thrombocytopenic purpura (Treatment-experienced) in Europe and Turkey in 2021 [175] | 13 Jul 2020 |
| 15 Jul 2021 | Trial Update | Vanderbilt University Medical Center and National Institutes of Health plans the phase II/III NECTAR (ACTIV-4 Host Tissue) trial in COVID-2019 infections in USA (NCT04924660) (700338546) [91] | 21 Aug 2021 |
| 30 Jun 2021 | Regulatory Status | Rigel Pharmaceuticals expects a decision from the Isreal ministry of Health for Idiopathic thrombocytopenic purpura during Q2 2021. [27] | 25 Nov 2020 |
| 31 Mar 2021 | Regulatory Status | Medison intends to launch TAVALISSE in Canada for Idiopathic thrombocytopenic purpura in Q1 2021. [27] | 31 May 2021 |
| 31 Dec 2020 | Trial Update | Rigel Pharmaceuticals plans a phase III clinical trial of Fostamatinib in COVID-19 infection (PO) in December 2020 (NCT04629703) (700329754) [65] | 02 Feb 2021 |
| 31 Dec 2019 | Regulatory Status | Rigel Pharmaceuticals anticipates CHMP opinion for Idiopathic thrombocytopenic purpura by the fourth quarter of 2019 [25] | 27 Jan 2020 |
| 31 Dec 2019 | Regulatory Status | Rigel Pharmaceuticals anticipates a final decision for its MAA for Idiopathic thrombocytopenic purpura in European Union by the end of 2019 [42] | 27 Jan 2020 |
| 30 Jun 2019 | Trial Update | Rigel Pharmaceuticals plans to initiate a phase III trial for fostamatinib in Autoimmune haemolytic anaemia (AHM) in USA, Europe, Canada and Australia in first half of 2019 (NCT03764618) (700301231) [178] | 08 Apr 2019 |
| 31 May 2018 | Regulatory Status | Rigel Pharmaceuticals expects to launch fostamatinib for Immune thrombocytopenic purpura in USA by late May 2018 [12] | 30 May 2018 |
| 17 Apr 2018 | Regulatory Status | The US FDA assigns PDUFA action date of 17/April/2018 for fostamatinib disodium for Immune thrombocytopenic purpura [15] | 18 Apr 2018 |
| 01 Oct 2017 | Trial Update | Rigel Pharmaceuticals, in collaboration with Sidney Kimmel Comprehensive Cancer Center plans a phase I trial for Ovarian cancer (Combination therapy, In adults, In the elderly, Late-stage disease, Recurrent) in USA (NCT03246074) | 18 Feb 2018 |
| 01 Jun 2017 | Regulatory Status | Rigel Pharmaceuticals expects to receives notification regarding the NDA acceptance from the FDA for fostamatinib in Immune thrombocytopenic purpura, by June 2017 (9214754) | 26 Jun 2017 |
Development History
| Event Date | Update Type | Comment |
|---|---|---|
| 06 Feb 2024 | Phase Change - Preregistration | Preregistration for Idiopathic thrombocytopenic purpura in South Korea (PO), prior to February 2024 (Kissei Pharmaceutical pipeline, February 2024) Updated 15 Feb 2024 |
| 31 Dec 2023 | Patent Information | Rigel Pharmaceuticals has patent protection for Fostamatinib in USA, Japan, Europe and multiple countries Worldwide [89] Updated 12 Mar 2024 |
| 31 Dec 2023 | Regulatory Status | Rigel Pharmaceuticals decides not to submit an Emergency Use Authorization or sNDA for COVID-2019 infections [89] Updated 12 Mar 2024 |
| 31 Dec 2023 | Trial Update | Vanderbilt University Medical Center completes the phase II/III NECTAR trial in COVID-2019 infections in USA and Italy (NCT04924660) Updated 15 Feb 2024 |
| 10 Dec 2023 | Scientific Update | Efficacy and adverse events data from a phase-III trial in Idiopathic thrombocytopenic purpura presented at the 65th American Society of Hematology Annual Meeting and Exposition (ASH-Hem-2023) [38] Updated 30 Jan 2024 |
| 05 Nov 2023 | Financial Update | Credit Suisse financial data update Updated 05 Nov 2023 |
| 11 Oct 2023 | Scientific Update | Updated efficacy and adverse event data from the phase III FOCUS trial in COVID-2019 infections presented at the IDWeek 2023 (IDW-2023) [100] [101] Updated 13 Oct 2023 |
| 30 Sep 2023 | Regulatory Status | Data and Safety Monitoring Board (DSMB) recommends to cease enrollment in phase III NECTAR (ACTIV-4 Host Tissue) trial in COVID-2019 infections [92] Updated 09 Nov 2023 |
| 25 Sep 2023 | Trial Update | Kissei Pharmaceutical completes a phase III trial for Idiopathic thrombocytopenic purpura (Treatment-experienced) in Japan (PO) (NCT04132050) (JapicCTI-195001) Updated 03 Jan 2024 |
| 28 Jul 2023 | Phase Change - No development reported | No recent reports of development identified for research development in Waldenstrom's macroglobulinaemia in USA (PO) Updated 28 Jul 2023 |
| 02 Jun 2023 | Scientific Update | Efficacy and adverse events data from a phase I trial in Ovarian cancer presented at the 59th Annual Meeting of the American Society of Clinical Oncology (ASCO-2023) [110] Updated 08 Jul 2023 |
| 07 Apr 2023 | Regulatory Status | Fostamatinib - Rigel Pharmaceuticals receives Orphan Drug status for Idiopathic thrombocytopenic purpura in South Korea before April 2023 [28] Updated 11 Apr 2023 |
| 06 Apr 2023 | Phase Change - Marketed | Launched for Idiopathic thrombocytopenic purpura in Japan (PO) (Tablet, 100 mg) [28] Updated 11 Apr 2023 |
| 06 Apr 2023 | Phase Change - Marketed | Launched for Idiopathic thrombocytopenic purpura in Japan (PO) (Tablet, 150 mg) [28] Updated 11 Apr 2023 |
| 28 Mar 2023 | Phase Change - Marketed | Launched for Idiopathic thrombocytopenic purpura (Treatment-experienced) in Israel (PO) [32] (SEC FILING#2023) Updated 28 Mar 2023 |
| 28 Mar 2023 | Phase Change - Registered | Registered for Idiopathic thrombocytopenic purpura (Treatment-experienced) in Israel (PO) Updated 28 Mar 2023 |
| 31 Dec 2022 | Phase Change - Preregistration | Preregistration for Idiopathic thrombocytopenic purpura in Argentina (PO) [34] [33] Updated 01 Sep 2023 |
| 31 Dec 2022 | Phase Change - Preregistration | Preregistration for Idiopathic thrombocytopenic purpura in Brazil (PO) [34] [33] Updated 01 Sep 2023 |
| 31 Dec 2022 | Phase Change - Preregistration | Preregistration for Idiopathic thrombocytopenic purpura in Colombia (PO) [34] [33] Updated 01 Sep 2023 |
| 31 Dec 2022 | Phase Change - Preregistration | Preregistration for Idiopathic thrombocytopenic purpura in Mexico (PO) [34] [33] Updated 01 Sep 2023 |
| 31 Dec 2022 | Phase Change - Marketed | Launched for Idiopathic thrombocytopenic purpura (Treatment-experienced) in Norway, Czech Republic, Denmark, Netherlands (PO), prior to December 2022 [18] Updated 05 Jun 2023 |
| 23 Dec 2022 | Phase Change - Registered | Registered for Idiopathic thrombocytopenic purpura in Japan (PO) [29] Updated 02 Jan 2023 |
| 10 Dec 2022 | Scientific Update | Efficacy and adverse events data from a phase-III FORWARD trial in Autoimmune haemolytic anaemia presented at the 64th American Society of Hematology Annual Meeting and Exposition (ASH-Hem-2022) [71] Updated 20 Jan 2023 |
| 01 Nov 2022 | Scientific Update | Top-line safety and efficacy data from a phase III FOCUS trial in COVID-2019 infections released by Rigel Pharmaceuticals [99] Updated 03 Nov 2022 |
| 19 Oct 2022 | Regulatory Status | NICE recommends fostamatinib for treating refractory chronic immune thrombocytopenia [31] Updated 31 Oct 2022 |
| 10 Oct 2022 | Regulatory Status | Rigel Pharmaceuticals does not intend to file a supplemental New Drug Application (sNDA) for Autoimmune haemolytic anaemia [60] Updated 12 Oct 2022 |
| 05 Sep 2022 | Trial Update | Rigel Pharmaceuticals completes a phase III FOCUS trial in COVID-2019 infections (Adjunctive treatment) in the US, Argentina, Brazil and Mexico (NCT04629703) Updated 18 Apr 2023 |
| 24 Aug 2022 | Phase Change - II/III | Phase-II/III clinical trials in COVID-2019 Infections in Italy (PO) (EudraCT2022-000715-31) Updated 15 Feb 2024 |
| 04 Aug 2022 | Regulatory Status | Inmagene Biopharmaceuticals plans to submit a New Drug Application for fostamatinib for the treatment of idiopathic thrombocytopenic purpura in Hong Kong (Kissei pipeline, August 2022) Updated 04 Aug 2022 |
| 31 Jul 2022 | Trial Update | Rigel Pharmaceuticals completes enrolment in the phase III trial of Fostamatinib in COVID-19 infection (PO) [1] Updated 04 Aug 2022 |
| 08 Jun 2022 | Scientific Update | Safety and efficacy data from a phase III trial in Autoimmune haemolytic anaemia released by Rigel Pharmaceuticals [70] Updated 15 Jun 2022 |
| 31 May 2022 | Company Involvement | Rigel Pharmaceuticals and Knight Therapeutics enters into a commercial license agreement for the commercialisation of fostamatinib in all indications in Latin America [1] Updated 04 Aug 2022 |
| 28 Apr 2022 | Phase Change - Preregistration | Preregistration for Idiopathic thrombocytopenic purpura in Japan (PO) [30] Updated 01 May 2022 |
| 11 Apr 2022 | Trial Update | Rigel Pharmaceuticals completes a phase III FORWARD trial in Autoimmune haemolytic anaemia (Treatment-experienced) in US, Australia, Austria, Belarus, Belgium, Bulgaria, Canada, Czech Republic, Denmark, France, Georgia, Germany, Hungary, Italy, Netherlands, Norway, Romania, Russia, Serbia, Spain, UK and Ukraine (PO) (NCT03764618) (EudraCT2018-004774-97) Updated 23 Jan 2023 |
| 11 Mar 2022 | Regulatory Status | Rigel Pharmaceuticals plans to launch Fostamatinib for Autoimmune haemolytic anaemia in 2023 [88] Updated 11 Mar 2022 |
| 08 Mar 2022 | Scientific Update | Updated efficacy and safety data from the phase II SOAR trial in Autoimmune haemolytic anaemia released by Rigel Pharmaceuticals [88] Updated 11 Mar 2022 |
| 22 Feb 2022 | Trial Update | Duke University completes a phase I clinical trial in Graft-versus-host disease in USA (PO) (NCT02611063) Updated 27 Mar 2023 |
| 03 Feb 2022 | Regulatory Status | JW Pharmaceutical plans to submit a New Drug Application for fostamatinib for the treatment of idiopathic thrombocytopenic purpura in South Korea (Kissei pipeline, February 2022) Updated 04 Feb 2022 |
| 03 Feb 2022 | Trial Update | Inmagene Biopharmaceutical plans a clinical trial in idiopathic thrombocytopenic purpura in China (Kissei pipeline, February 2022) Updated 04 Feb 2022 |
| 21 Dec 2021 | Scientific Update | Top-line efficacy and adverse events data from a phase III trial in Idiopathic thrombocytopenic purpura released by Kissei Pharmaceutical [37] Updated 28 Dec 2021 |
| 30 Nov 2021 | Phase Change - III | Phase-III clinical trials in COVID-2019 infections (Adjunctive treatment) in Mexico (PO) (NCT04629703) Updated 05 Aug 2022 |
| 19 Nov 2021 | Trial Update | Rigel Pharmaceuticals completes enrolment of a phase III FORWARD trial in Autoimmune haemolytic anaemia, in the US, Australia, Georgia, Austria, Belarus, Belgium, Bulgaria, Canada, Czech Republic, Denmark, France, Georgia, Germany, Hungary, Italy, Netherlands, Norway, Romania, Russia, Serbia, Spain, UK and Ukraine [62] Updated 19 Nov 2021 |
| 17 Nov 2021 | Biomarker Update | Biomarkers information updated Updated 19 Nov 2021 |
| 29 Sep 2021 | Scientific Update | Adverse events data from phase III trial in COVID-2019 infections presented at the IDWeek 2021 (IDW-2021) [96] Updated 07 Feb 2022 |
| 28 Sep 2021 | Phase Change - Marketed | Launched for Idiopathic thrombocytopenic purpura (Treatment-experienced) in France, Italy and Spain (PO) [19] Updated 30 Sep 2021 |
| 28 Sep 2021 | Regulatory Status | Grifols plans to launch fostamatinib in Czech Republic and in Nordic countries [19] Updated 30 Sep 2021 |
| 03 Sep 2021 | Scientific Update | Efficacy and adverse events data of a phase II trial in COVID-2019 infections published in Clinical Infectious Diseases [106] Updated 03 Sep 2021 |
| 04 Aug 2021 | Licensing Status | Kissei Pharmaceutical out-licenses fostamatinib to Inmagene in China, Hong Kong and Macau [2] Updated 10 Aug 2021 |
| 15 Jul 2021 | Phase Change - II/III | Phase-II/III clinical trials in COVID-2019 infections in USA (PO) (NCT04924660) [90] Updated 21 Aug 2021 |
| 30 Jun 2021 | Licensing Status | Kissei Pharmaceutical out-licenses fostamatinib to JW Pharmaceutical in South Korea [3] Updated 30 Jun 2021 |
| 29 Jun 2021 | Trial Update | Vanderbilt University Medical Center and National Institutes of Health plans the phase II/III NECTAR (ACTIV-4 Host Tissue) trial in COVID-2019 infections in USA (NCT04924660) [91] Updated 21 Aug 2021 |
| 31 May 2021 | Phase Change - Preregistration | Preregistration for emergency use authorization (EUA) in COVID-2019 infections (Adjunctive treatment) in USA (PO) [91] [69] Updated 07 Jul 2021 |
| 05 May 2021 | Trial Update | Kissei Pharmaceutical completes enrolment in phase III trials in Idiopathic thrombocytopenic purpura in Japan (PO) [40] Updated 17 May 2021 |
| 05 May 2021 | Trial Update | Rigel Pharmaceuticals completes enrolment in a phase-III trial in Autoimmune haemolytic anaemia (Treatment-experienced) in United Kingdom, Spain, Serbia, Norway, Italy, Hungary, France, Germany, Denmark, Czech Republic, Canada, Belgium, Austria (PO) [40] Updated 17 May 2021 |
| 03 May 2021 | Trial Update | National Heart, Lung, and Blood Institute completes a phase II trial COVID-2019 infection (Adjunctive treatment) in USA (PO) (NCT04579393) Updated 19 May 2021 |
| 01 May 2021 | Patent Information | Rigel pharmaceuticals has patent protection for fostamatinib covering composition of matter patent in USA [174] Updated 03 Jun 2021 |
| 01 May 2021 | Patent Information | Rigel pharmaceuticals has patent protection for fostamatinib covering composition of matter, methods for use, formulations, methods for making patent in USA [174] Updated 03 Jun 2021 |
| 01 May 2021 | Patent Information | Rigel pharmaceuticals has patent protection for fostamatinib covering composition of matter and in compositions for use treating various diseases in European Union [174] Updated 03 Jun 2021 |
| 01 May 2021 | Patent Information | Rigel pharmaceuticals has pending patents for fostamatinib in foreign jurisdictions [174] Updated 03 Jun 2021 |
| 13 Apr 2021 | Scientific Update | Top-line efficacy and adverse events data from a phase II trial in COVID-2019 infections released by Rigel Pharmaceuticals [102] Updated 28 Jul 2021 |
| 28 Mar 2021 | Phase Change - No development reported | No recent reports of development identified for phase-I development in Ovarian-cancer(Combination therapy, In the elderly, Recurrent, Second-line therapy or greater, In adults) in USA (PO, Tablet) Updated 28 Mar 2021 |
| 11 Mar 2021 | Trial Update | Rigel Pharmaceuticals completes enrolment in its phase II trial in COVID-2019 infections in the US [103] Updated 22 Mar 2021 |
| 22 Feb 2021 | Phase Change - III | Phase-III clinical trials in COVID-2019 infections (Adjunctive treatment) in Brazil, Argentina (PO) (NCT04629703) Updated 07 Jul 2021 |
| 29 Jan 2021 | Phase Change - III | Phase-III clinical trials in COVID-2019 infections (Adjunctive treatment) in USA (PO) [94] (NCT04629703) Updated 02 Feb 2021 |
| 29 Jan 2021 | Regulatory Status | Rigel Pharmaceuticals plans to file for Emergency Use Authorization for COVID-2019 infections in the US [94] Updated 02 Feb 2021 |
| 28 Jan 2021 | Phase Change - No development reported | No recent reports of development identified for phase-I development in Graft-versus-host-disease in USA (PO) Updated 28 Jan 2021 |
| 11 Jan 2021 | Regulatory Status | Fostamatinib - Rigel Pharmaceuticals receives Fast Track designation for Autoimmune haemolytic anaemia [PO] (Treatment-experienced) in USA [40] Updated 17 May 2021 |
| 07 Jan 2021 | Phase Change - Marketed | Launched for Idiopathic thrombocytopenic purpura (Treatment-experienced) in Canada (PO) before January 2021 [26] Updated 12 Jan 2021 |
| 23 Nov 2020 | Regulatory Status | Medison intends to launch TAVALISSE in Canada for Idiopathic thrombocytopenic purpura in Q1 2021. [27] Updated 31 May 2021 |
| 23 Nov 2020 | Phase Change - Preregistration | Preregistration for Idiopathic thrombocytopenic purpura (Treatment-experienced) in Canada (PO) before November 2020 [27] Updated 25 Nov 2020 |
| 23 Nov 2020 | Phase Change - Preregistration | Preregistration for Idiopathic thrombocytopenic purpura in Israel (PO) before November 2020 [27] Updated 25 Nov 2020 |
| 23 Nov 2020 | Phase Change - Registered | Registered for Idiopathic thrombocytopenic purpura (Treatment-experienced) in Canada (PO) [27] Updated 25 Nov 2020 |
| 23 Nov 2020 | Regulatory Status | Rigel Pharmaceuticals expects a decision from the Isreal ministry of Health for Idiopathic thrombocytopenic purpura during Q2 2021. [27] Updated 25 Nov 2020 |
| 05 Nov 2020 | Trial Update | Rigel Pharmaceuticals plans a phase III clinical trial of Fostamatinib in COVID-19 infection (PO) in December 2020 (NCT04629703) [65] Updated 02 Feb 2021 |
| 17 Sep 2020 | Phase Change - II | Phase-II clinical trials in COVID-2019 infections (Adjunctive treatment) in USA (PO) [104] Updated 23 Sep 2020 |
| 14 Jul 2020 | Phase Change - II/III | Phase-II/III clinical trials in COVID-19 pneumonia in United Kingdom (PO) [108] (EudraCT2020-001750-22) Updated 16 Jul 2020 |
| 09 Jul 2020 | Phase Change - Marketed | Launched for Idiopathic thrombocytopenic purpura (Treatment-experienced) in Germany, United Kingdom (PO) [175] Updated 13 Jul 2020 |
| 09 Jul 2020 | Regulatory Status | Grifols plans to launch fostamatinib for Idiopathic thrombocytopenic purpura (Treatment-experienced) in Europe and Turkey in 2021 [175] Updated 13 Jul 2020 |
| 01 Jun 2020 | Trial Update | Rigel Pharmaceuticals completes a phase III extension trial for Immune thrombocytopenic purpura in USA, Australia, Austria, Bulgaria, Canada, Czech Republic, Denmark, Hungary, Italy, Netherlands, Norway, Poland, Romania, Spain and United Kingdom (NCT02077192) (EudraCT2013-005454-30) Updated 01 Jun 2021 |
| 29 May 2020 | Scientific Update | Efficacy and adverse events data from a phase II trial in Diffuse large B-cell lymphoma presented at the 56th Annual Meeting of the American Society of Clinical Oncology (ASCO-2020) [176] Updated 28 Jun 2020 |
| 29 Feb 2020 | Regulatory Status | Fostamatinib receives Orphan Drug status for Idiopathic thrombocytopenic purpura in Japan [5] Updated 04 Mar 2020 |
| 16 Jan 2020 | Phase Change - Registered | Registered for Idiopathic thrombocytopenic purpura (Treatment-experienced) in Norway, Liechtenstein, Iceland, European Union (PO) [20] Updated 17 Jan 2020 |
| 31 Dec 2019 | Trial Update | Rigel Pharmaceuticals completes a phase-II clinical trial in Autoimmune haemolytic anaemia in the USA and Canada (PO) (NCT02612558) Updated 27 Jul 2021 |
| 24 Dec 2019 | Trial Update | Kissei Pharmaceutical initiates enrolment in a phase III trial for Idiopathic thrombocytopenic purpura (Treatment-experienced) in Japan (PO) (NCT04132050) (JapicCTI-195001) Updated 28 Dec 2021 |
| 05 Dec 2019 | Scientific Update | Updated safety data from the phase II SOAR trial in Autoimmune haemolytic anaemia released by Rigel Pharmaceuticals [87] Updated 05 Dec 2019 |
| 15 Nov 2019 | Regulatory Status | The CHMP issues positive opinion for the approval of fostamatinib for the treatment of Idiopathic thrombocytopenic purpura in European Union [21] Updated 20 Nov 2019 |
| 07 Nov 2019 | Scientific Update | Updated efficacy data from the phase II SOAR trial in Autoimmune haemolytic anaemia released by Rigel Pharmaceuticals [84] Updated 20 Nov 2019 |
| 05 Nov 2019 | Regulatory Status | Rigel Pharmaceuticals announces intention to launch fostamatinib for Idiopathic thrombocytopenic purpura in Europe, Japan, and Canada Updated 13 Nov 2019 |
| 30 Oct 2019 | Trial Update | Rigel Pharmaceuticals initiates enrollment in a phase III trial for Autoimmune haemolytic anaemia (Treatment-experienced) in USA, Australia, Austria, Belarus, Belgium, Bulgaria, France, Czech Republic, Georgia, Germany, Italy, Netherlands, Norway, Russia, Serbia, Spain, Ukraine, United Kingdom, Hungary (NCT04138927) Updated 12 Jun 2021 |
| 25 Oct 2019 | Trial Update | Rigel Pharmaceuticals plans a phase III trial for Autoimmune haemolytic anaemia (Treatment-experienced)(NCT04138927) Updated 05 Nov 2019 |
| 24 Oct 2019 | Regulatory Status | 9277197 - updated KDM, created HE and FET Updated 24 Oct 2019 |
| 18 Oct 2019 | Regulatory Status | The CHMP adopts positive trend vote on MAA for fostamatinib for Idiopathic thrombocytopenic purpura (Treatment-experienced) [22] Updated 24 Oct 2019 |
| 02 Oct 2019 | Licensing Status | Fostamatinib licensed to Medison Pharma in Canada and Israel [6] Updated 09 Oct 2019 |
| 23 Sep 2019 | Regulatory Status | Kissei Pharmaceuticals plans to submit a NDA with Pharmaceuticals and Medical Devices Agency (PMDA) for Idiopathic thrombocytopenic purpura in late 2021 or early 2022. [41] Updated 02 Jan 2023 |
| 23 Sep 2019 | Phase Change - III | Phase-III clinical trials in Idiopathic thrombocytopenic purpura in Japan (PO) [41] Updated 25 Sep 2019 |
| 23 Sep 2019 | Regulatory Status | Kissei Pharmaceuticals submits a Clinical Trial Application for a phase III trial of fostamatinib in Idiopathic thrombocytopenic purpura in Japan before September 2019 [41] Updated 25 Sep 2019 |
| 23 Sep 2019 | Regulatory Status | Pharmaceuticals and Medical Devices Agency (PMDA) approves a Clinical Trial Application for a phase III trial for fostamatinib in Idiopathic thrombocytopenic purpura in Japan before September 2019 [41] Updated 25 Sep 2019 |
| 13 Jun 2019 | Scientific Update | Efficacy and adverse events data from the extension period of the phase II SOAR trial in Autoimmune haemolytic anaemia presented at the 24th Congress of the European Haematology Association (EHA-2019) [85] Updated 03 Sep 2019 |
| 04 Jun 2019 | Scientific Update | Preclinical data for Waldenstrom's macroglobulinaemia presented at the 55th Annual Meeting of the American Society of Clinical Oncology (ASCO-2019) [112] Updated 12 Jun 2019 |
| 01 Jun 2019 | Phase Change | Early research in Waldenstrom's macroglobulinaemia in USA (unspecified route) [112] Updated 12 Jun 2019 |
| 07 May 2019 | Regulatory Status | Kissei Pharmaceuticals initiates discussions with Pharmaceuticals and Medical Devices Agency (PMDA) regarding the establishment of a regulatory path for fostamatinib in Idiopathic thrombocytopenic purpura in Japan [24] Updated 13 May 2019 |
| 07 May 2019 | Regulatory Status | Rigel Pharmaceuticals responds to day-120 questions of EMA related to its already-filed MAA for Idiopathic thrombocytopenic purpura [24] Updated 13 May 2019 |
| 04 Apr 2019 | Phase Change - III | Phase-III clinical trials in Autoimmune haemolytic anaemia (Treatment-experienced) in Australia, Georgia, Russia (PO) (NCT03764618) Updated 27 Jan 2020 |
| 04 Apr 2019 | Phase Change - III | Phase-III clinical trials in Autoimmune haemolytic anaemia (Treatment-experienced) in USA (PO) (NCT03764618) Updated 08 Apr 2019 |
| 01 Apr 2019 | Phase Change - III | Phase-III clinical trials in Autoimmune haemolytic anaemia (Treatment-experienced) in Ukraine, Romania, Netherlands, Bulgaria, Belarus (PO) (NCT03764618) Updated 07 Jul 2021 |
| 01 Apr 2019 | Phase Change - III | Phase-III clinical trials in Autoimmune haemolytic anaemia (Treatment-experienced) in United Kingdom, Spain, Serbia, Norway, Italy, Hungary, France, Germany, Denmark, Czech Republic, Canada, Belgium, Austria (PO) (NCT03764618) [63] Updated 28 Dec 2020 |
| 23 Jan 2019 | Licensing Status | Rigel Pharmaceuticals and Grifols enters into collaboration and licence agreement to commercialise fostamatinib in Europe and Turkey [4] Updated 28 Jan 2019 |
| 07 Jan 2019 | Regulatory Status | Rigel Pharmaceuticals anticipates a final decision for its MAA for Idiopathic thrombocytopenic purpura in European Union by the end of 2019 [42] Updated 27 Jan 2020 |
| 06 Jan 2019 | Scientific Update | Efficacy and safety data from a phase III open-label extension study in Idiopathic thrombocytopenic purpura presented at the 60th Annual Meeting and Exposition of the American Society of Hematology (ASH-Hem-2018) [55] Updated 06 Jan 2019 |
| 05 Jan 2019 | Active Status Review | update only, already reviewed; 3368086: Updated KDM, TT, AE and HE Updated 05 Jan 2019 |
| 01 Dec 2018 | Scientific Update | Safety and efficcay data from the extension period of the phase II SOAR trial in Autoimmune haemolytic anaemia presented at the 60th Annual Meeting and Exposition of the American Society of Hematology (ASH-Hem-2018) [86] Updated 05 Jan 2019 |
| 01 Dec 2018 | Scientific Update | Exploratory analyses data from phase III trials in Idiopathic thrombocytopenic purpura presented at the 60th Annual Meeting and Exposition of the American Society of Hematology (ASH-Hem-2018) [177] Updated 03 Jan 2019 |
| 21 Nov 2018 | Phase Change - Discontinued(II) | Discontinued - Phase-II for IgA nephropathy in Austria, Germany, Hong Kong, Switzerland, Taiwan, United Kingdom, Singapore, USA (PO) Updated 21 Nov 2018 |
| 06 Nov 2018 | Trial Update | Rigel Pharmaceuticals plans to initiate a phase III trial for fostamatinib in Autoimmune haemolytic anaemia (AHM) in USA, Europe, Canada and Australia in first half of 2019 (NCT03764618) [178] Updated 08 Apr 2019 |
| 06 Nov 2018 | Regulatory Status | European Medicines Agency accepts the marketing authorisation application (MAA) for Idiopathic thrombocytopenic purpura [178] Updated 15 Mar 2019 |
| 30 Oct 2018 | Trial Update | Rigel Pharmaceuticals plans a phase III trial for Autoimmune hemolytic anemia Updated 05 Nov 2018 |
| 29 Oct 2018 | Licensing Status | Fostamatinib licensed to Kissei Pharmaceutical in Japan, China, Taiwan and the Republic of Korea [7] Updated 06 Nov 2018 |
| 11 Oct 2018 | Regulatory Status | Rigel Pharmaceuticals anticipates CHMP opinion for Idiopathic thrombocytopenic purpura by the fourth quarter of 2019 [25] Updated 27 Jan 2020 |
| 04 Oct 2018 | Regulatory Status | EMA validates the marketing authorization application for fostamatinib for Idiopathic thrombocytopenic purpura in European Union (PO) [25] Updated 28 Jan 2019 |
| 04 Oct 2018 | Phase Change - Preregistration | Preregistration for Idiopathic thrombocytopenic purpura (Treatment-experienced) in European Union (PO) [25] before October 2018 Updated 17 Oct 2018 |
| 29 May 2018 | Phase Change - Marketed | Launched for Idiopathic thrombocytopenic purpura (Treatment-experienced) in USA (PO) - First global launch [11] Updated 30 May 2018 |
| 17 Apr 2018 | Regulatory Status | Rigel Pharmaceuticals expects to launch fostamatinib for Immune thrombocytopenic purpura in USA by late May 2018 [12] Updated 30 May 2018 |
| 17 Apr 2018 | Phase Change - Registered | Registered for Idiopathic thrombocytopenic purpura (Treatment-experienced) in USA (PO) - First global approval [12] Updated 18 Apr 2018 |
| 13 Apr 2018 | Other | Immune thrombocytopenic purpura is now called Idiopathic thrombocytopenic purpura Updated 13 Apr 2018 |
| 04 Apr 2018 | Scientific Update | Efficacy and adverse events data from a phase II trial in IgA Nephropathy released by Rigel Pharmaceuticals [113] Updated 10 Apr 2018 |
| 06 Mar 2018 | Scientific Update | Updated efficacy data from the phase II SOAR trial in Autoimmune haemolytic anaemia released by Rigel Pharmaceuticals [72] Updated 12 Mar 2018 |
| 01 Feb 2018 | Phase Change - I | Phase-I clinical trials in Ovarian cancer (Second-line therapy or greater, Recurrent, Combination therapy, In adults, In the elderly) in USA (PO) Updated 18 Feb 2018 |
| 31 Jan 2018 | Regulatory Status | Fostamatinib - Rigel Pharmaceuticals receives Orphan Drug status for Autoimmune haemolytic anaemia in USA [72] Updated 12 Mar 2018 |
| 04 Jan 2018 | Scientific Update | Interim efficacy data from a phase II trial in Autoimmune haemolytic anaemia released by Rigel Pharmaceuticals [83] Updated 09 Jan 2018 |
| 06 Dec 2017 | Trial Update | Rigel Pharmaceuticals initiates an expanded-access programme for Immune Thrombocytopenic Purpura (Late-stage disease) (NCT03363334) Updated 11 Dec 2017 |
| 07 Nov 2017 | Scientific Update | Updated adverse events data from a phase II trial in Autoimmune haemolytic anaemia released by Rigel Pharmaceuticals [75] Updated 14 Nov 2017 |
| 03 Oct 2017 | Scientific Update | Efficacy and adverse events data from a phase II trial in Autoimmune haemolytic anaemia released by Rigel Pharmaceuticals [76] Updated 07 Oct 2017 |
| 09 Aug 2017 | Trial Update | Rigel Pharmaceuticals, in collaboration with Sidney Kimmel Comprehensive Cancer Center plans a phase I trial for Ovarian cancer (Combination therapy, In adults, In the elderly, Late-stage disease, Recurrent) in USA (NCT03246074) Updated 18 Feb 2018 |
| 02 Aug 2017 | Trial Update | Rigel Pharmaceuticals completes enrolment in its phase II trial for IgA nephropathy in Austria, Germany, Hong Kong, Singapore, Switzerland, Taiwan, United Kingdom (PO) (NCT02112838) [83] Updated 09 Jan 2018 |
| 22 Jun 2017 | Regulatory Status | The US FDA assigns PDUFA action date of 17/April/2018 for fostamatinib disodium for Immune thrombocytopenic purpura [15] Updated 18 Apr 2018 |
| 19 Jun 2017 | Regulatory Status | The US FDA accepts New Drug Application for fostamatinib disodium for the treatment of chronic Immune thrombocytopenic purpura [16] Updated 26 Jun 2017 |
| 27 Apr 2017 | Patent Information | Rigel Pharmaceuticals applies for federal registration of Tavalisse™ mark with US Patent and Trademark Office for fostamatinib in USA [14] Updated 04 May 2017 |
| 17 Apr 2017 | Regulatory Status | Rigel Pharmaceuticals expects to receives notification regarding the NDA acceptance from the FDA for fostamatinib in Immune thrombocytopenic purpura, by June 2017 [17] Updated 26 Jun 2017 |
| 17 Apr 2017 | Phase Change - Preregistration | Preregistration for Idiopathic thrombocytopenic purpura in USA (PO) [17] Updated 20 Apr 2017 |
| 07 Mar 2017 | Scientific Update | Efficacy data from the FIT phase III trials , 048 and 049 studies) for Immune thrombocytopenic purpura released by Rigel Pharmaceuticals [44] Updated 10 Mar 2017 |
| 30 Jan 2017 | Scientific Update | Efficacy data from phase III Study 049 in Immune thrombocytopenic purpura released by Rigel Pharmaceuticals [45] Updated 03 Feb 2017 |
| 30 Jan 2017 | Scientific Update | Pooled efficacy data from phase III Study 047 and 048 in Immune thrombocytopenic purpura released by Rigel Pharmaceuticals [45] Updated 03 Feb 2017 |
| 20 Oct 2016 | Scientific Update | Efficacy and adverse events data from the phase III FIT 2 trial in Immune thrombocytopenic purpura released by Rigel Pharmaceuticals [52] Updated 24 Oct 2016 |
| 20 Oct 2016 | Scientific Update | Efficacy data from the FIT phase III long-term extension study 049 in Immune thrombocytopenic purpura released by Rigel Pharmaceuticals [52] Updated 24 Oct 2016 |
| 30 Aug 2016 | Scientific Update | Interim adverse events data from a phase III trial in immune thrombocytopenia released by Rigel Pharmaceuticals [46] Updated 01 Sep 2016 |
| 30 Aug 2016 | Scientific Update | Interim efficacy data from a phase III trial in immune thrombocytopenia released by Rigel Pharmaceuticals [46] Updated 01 Sep 2016 |
| 01 Aug 2016 | Trial Update | Rigel Pharmaceuticals completes the phase-III FIT 2 trial for Immune thrombocytopenic purpura in the US, Austria, Bulgaria, Czech Republic, Germany, Norway, Poland, Romania and Spain (NCT02076412) Updated 29 Nov 2016 |
| 03 May 2016 | Regulatory Status | Rigel Pharmaceuticals announces intention to submit NDA to US FDA in 1Q 2017 Updated 09 May 2016 |
| 01 Apr 2016 | Trial Update | Rigel completes the phase III FIT 1 trial for Immune thrombocytopenic purpura in USA, Australia, Canada, Denmark, Hungary, Italy, the Netherlands, the UK (NCT02076399) Updated 10 Aug 2016 |
| 01 Apr 2016 | Trial Update | Rigel Pharmaceuticals completes enrolment in the phase-III FIT trials for Immune thrombocytopenic purpura in the US, Austria, Australia, Bulgaria, Poland, the Netherlands, Norway, the Czech Republic, Canada, Denmark, Hungary, Italy and the UK (NCT02076399 & NCT02076412) [53] Updated 05 Apr 2016 |
| 08 Mar 2016 | Patent Information | Rigel Pharmaceuticals has patent protection for fostamatinib (R 406) in USA (Rigel Pharmaceuticals 10-K, March 2016) Updated 30 May 2016 |
| 08 Mar 2016 | Patent Information | Rigel Pharmaceuticals has patents pending for fostamatinib (R 406) in other countries, except for USA (Rigel Pharmaceuticals 10-K, March 2016) Updated 30 May 2016 |
| 25 Feb 2016 | Phase Change - II | Phase-II clinical trials in Autoimmune haemolytic anaemia in Canada (PO) after February 2016 (NCT02612558) Updated 23 Apr 2018 |
| 25 Feb 2016 | Phase Change - II | Phase-II clinical trials in Autoimmune haemolytic anaemia in USA (PO) (NCT02612558) [80] Updated 27 Feb 2016 |
| 07 Jan 2016 | Licensing Status | Fostamatinib is available for licensing in Asia as of 07 Jan 2016. www.rigel.com Updated 09 Jan 2016 |
| 01 Jan 2016 | Phase Change - I | Phase-I clinical trials in Graft-versus-host disease in USA (PO) after January 2016 (NCT02611063) Updated 05 Apr 2016 |
| 26 Nov 2015 | Trial Update | Rigel Pharmaceuticals plans a phase II trial for Autoimmune Haemolytic Anaemia (Treatment-resistant) in USA (PO) (NCT02612558) Updated 26 Nov 2015 |
| 23 Nov 2015 | Trial Update | Duke University plans a phase I trial for Graft versus host disease in USA (PO) (NCT02611063) Updated 23 Nov 2015 |
| 30 Sep 2015 | Trial Update | Rigel withdraws a phase II extension trial for IgA Nephropathy in Austria, Germany, Hong Kong, Singapore, Switzerland, Taiwan, United Kingdom and USA (NCT02433236) Updated 04 Nov 2015 |
| 08 Sep 2015 | Regulatory Status | Fostamatinib receives Orphan Drug status for Immune thrombocytopenic purpura in USA [35] Updated 10 Sep 2015 |
| 29 Apr 2015 | Trial Update | Rigel plans a phase II extension trial for IgA Nephropathy in Austria, Germany, Hong Kong, Singapore, Switzerland, Taiwan, United Kingdom and USA (NCT02433236) Updated 09 May 2015 |
| 01 Nov 2014 | Phase Change - III | Phase-III clinical trials in Idiopathic thrombocytopenic purpura in Norway (PO) after November 2014 (NCT02076412) Updated 10 Aug 2016 |
| 01 Nov 2014 | Phase Change - III | Phase-III clinical trials in Idiopathic thrombocytopenic purpura in Bulgaria and Poland (PO) after November 2014 (NCT02076412) Updated 26 Mar 2015 |
| 28 Oct 2014 | Phase Change - II | Phase-II clinical trials in IgA nephropathy in Germany, Hong Kong, Switzerland, Taiwan, United Kingdom (PO) (NCT02112838) after October 2014 Updated 09 May 2015 |
| 28 Oct 2014 | Phase Change - II | Phase-II clinical trials in IgA nephropathy in Austria (PO) Updated 03 Nov 2014 |
| 03 Oct 2014 | Phase Change - III | Phase-III clinical trials in Idiopathic thrombocytopenic purpura in Italy after October 2014 (PO) (NCT02076399) Updated 16 Jun 2015 |
| 03 Oct 2014 | Phase Change - III | Phase-III clinical trials in Idiopathic thrombocytopenic purpura in Netherlands (PO) Updated 03 Nov 2014 |
| 01 Oct 2014 | Phase Change - II | Phase-II clinical trials in IgA nephropathy in Singapore, USA (PO) [78] after October 2014 Updated 11 Jan 2017 |
| 11 Sep 2014 | Phase Change - III | Phase-III clinical trials in Idiopathic thrombocytopenic purpura in Czech Republic (PO) Updated 03 Nov 2014 |
| 23 Jul 2014 | Phase Change - III | Phase-III clinical trials in Idiopathic thrombocytopenic purpura in Austria (PO) Updated 14 Aug 2014 |
| 16 Jul 2014 | Trial Update | Rigel initiates a phase III trial for Immune thrombocytopenic purpura in USA (9165781; NCT02076412) Updated 21 Jul 2014 |
| 01 Jul 2014 | Trial Update | Rigel Pharmaceuticals initiates enrolment in a phase III extension trial for Immune thrombocytopenic purpura in Australia, Austria, Bulgaria, Canada, Czech Republic, Denmark, Hungary, Italy, Netherlands, Norway, Poland, Romania, Spain and United Kingdom after July 2014 (NCT02077192) Updated 23 Apr 2018 |
| 01 Jul 2014 | Trial Update | Rigel Pharmaceuticals initiates enrolment in a phase III extension trial for Immune thrombocytopenic purpura in USA (NCT02077192) Updated 12 Nov 2014 |
| 01 May 2014 | Phase Change - III | Phase-III clinical trials in Idiopathic thrombocytopenic purpura in Canada, Denmark, Hungary and United Kingdom (PO) after May 2014 (NCT02076399) Updated 26 Mar 2015 |
| 01 May 2014 | Phase Change - III | Phase-III clinical trials in Idiopathic thrombocytopenic purpura in USA (PO) (NCT02076399) Updated 13 Jun 2014 |
| 30 Apr 2014 | Phase Change | Investigation in IgA nephropathy in USA (PO) Updated 09 May 2014 |
| 10 Apr 2014 | Trial Update | Rigel plans a phase II trial for IgA nephropathy in Austria, Germany, Hong Kong, Singapore, Switzerland, Taiwan, United Arab Emirates and United Kingdom (NCT02112838) Updated 13 Jun 2014 |
| 26 Feb 2014 | Trial Update | Rigel Pharmaceuticals plans two phase III trials for Immune thrombocytopenic purpura in the US, Canada and EU (NCT02076399& NCT02076412) Updated 07 Mar 2014 |
| 29 Oct 2013 | Phase Change - Discontinued(II) | Discontinued - Phase-II for Chronic lymphocytic leukaemia in Italy (PO) Updated 10 Apr 2014 |
| 29 Oct 2013 | Phase Change - Discontinued(II) | Discontinued - Phase-II for Diffuse large B cell lymphoma in United Kingdom (PO) Updated 25 Mar 2014 |
| 29 Oct 2013 | Phase Change - Discontinued(II) | Discontinued - Phase-II for Diffuse large B cell lymphoma in USA (PO) Updated 29 Oct 2013 |
| 29 Oct 2013 | Phase Change - Discontinued(II) | Discontinued - Phase-II for Rheumatoid arthritis in Hong Kong (PO) Updated 29 Oct 2013 |
| 29 Oct 2013 | Phase Change - Discontinued(II) | Discontinued - Phase-II for Rheumatoid arthritis in Japan (PO) Updated 29 Oct 2013 |
| 29 Oct 2013 | Phase Change - Discontinued(II) | Discontinued - Phase-II for Rheumatoid arthritis in South Korea (PO) Updated 29 Oct 2013 |
| 29 Oct 2013 | Phase Change - Discontinued(II) | Discontinued - Phase-II for Rheumatoid arthritis in Taiwan (PO) Updated 29 Oct 2013 |
| 29 Oct 2013 | Phase Change - Discontinued(II) | Discontinued - Phase-II for Rheumatoid arthritis in Thailand (PO) Updated 29 Oct 2013 |
| 29 Oct 2013 | Phase Change - Discontinued(II) | Discontinued - Phase-II for Rheumatoid arthritis in Vietnam (PO) Updated 29 Oct 2013 |
| 29 Oct 2013 | Phase Change - Discontinued(II) | Discontinued - Phase-II for Solid tumours in USA (PO) Updated 29 Oct 2013 |
| 29 Oct 2013 | Phase Change - Discontinued(III) | Discontinued - Phase-III for Rheumatoid arthritis in Argentina (PO) Updated 29 Oct 2013 |
| 29 Oct 2013 | Phase Change - Discontinued(III) | Discontinued - Phase-III for Rheumatoid arthritis in Australia (PO) Updated 29 Oct 2013 |
| 29 Oct 2013 | Phase Change - Discontinued(III) | Discontinued - Phase-III for Rheumatoid arthritis in Belgium (PO) Updated 29 Oct 2013 |
| 29 Oct 2013 | Phase Change - Discontinued(III) | Discontinued - Phase-III for Rheumatoid arthritis in Brazil (PO) Updated 29 Oct 2013 |
| 29 Oct 2013 | Phase Change - Discontinued(III) | Discontinued - Phase-III for Rheumatoid arthritis in Bulgaria (PO) Updated 29 Oct 2013 |
| 29 Oct 2013 | Phase Change - Discontinued(III) | Discontinued - Phase-III for Rheumatoid arthritis in Canada (PO) Updated 29 Oct 2013 |
| 29 Oct 2013 | Phase Change - Discontinued(III) | Discontinued - Phase-III for Rheumatoid arthritis in Chile (PO) Updated 29 Oct 2013 |
| 29 Oct 2013 | Phase Change - Discontinued(III) | Discontinued - Phase-III for Rheumatoid arthritis in Colombia (PO) Updated 29 Oct 2013 |
| 29 Oct 2013 | Phase Change - Discontinued(III) | Discontinued - Phase-III for Rheumatoid arthritis in Czech Republic (PO) Updated 29 Oct 2013 |
| 29 Oct 2013 | Phase Change - Discontinued(III) | Discontinued - Phase-III for Rheumatoid arthritis in Estonia (PO) Updated 29 Oct 2013 |
| 29 Oct 2013 | Phase Change - Discontinued(III) | Discontinued - Phase-III for Rheumatoid arthritis in France (PO) Updated 29 Oct 2013 |
| 29 Oct 2013 | Phase Change - Discontinued(III) | Discontinued - Phase-III for Rheumatoid arthritis in Germany (PO) Updated 29 Oct 2013 |
| 29 Oct 2013 | Phase Change - Discontinued(III) | Discontinued - Phase-III for Rheumatoid arthritis in Hungary (PO) Updated 29 Oct 2013 |
| 29 Oct 2013 | Phase Change - Discontinued(III) | Discontinued - Phase-III for Rheumatoid arthritis in India (PO) Updated 29 Oct 2013 |
| 29 Oct 2013 | Phase Change - Discontinued(III) | Discontinued - Phase-III for Rheumatoid arthritis in Israel (PO) Updated 29 Oct 2013 |
| 29 Oct 2013 | Phase Change - Discontinued(III) | Discontinued - Phase-III for Rheumatoid arthritis in Italy (PO) Updated 29 Oct 2013 |
| 29 Oct 2013 | Phase Change - Discontinued(III) | Discontinued - Phase-III for Rheumatoid arthritis in Latvia (PO) Updated 29 Oct 2013 |
| 29 Oct 2013 | Phase Change - Discontinued(III) | Discontinued - Phase-III for Rheumatoid arthritis in Lithuania (PO) Updated 29 Oct 2013 |
| 29 Oct 2013 | Phase Change - Discontinued(III) | Discontinued - Phase-III for Rheumatoid arthritis in Mexico (PO) Updated 29 Oct 2013 |
| 29 Oct 2013 | Phase Change - Discontinued(III) | Discontinued - Phase-III for Rheumatoid arthritis in Netherlands (PO) Updated 29 Oct 2013 |
| 29 Oct 2013 | Phase Change - Discontinued(III) | Discontinued - Phase-III for Rheumatoid arthritis in Peru (PO) Updated 29 Oct 2013 |
| 29 Oct 2013 | Phase Change - Discontinued(III) | Discontinued - Phase-III for Rheumatoid arthritis in Poland (PO) Updated 29 Oct 2013 |
| 29 Oct 2013 | Phase Change - Discontinued(III) | Discontinued - Phase-III for Rheumatoid arthritis in Portugal (PO) Updated 29 Oct 2013 |
| 29 Oct 2013 | Phase Change - Discontinued(III) | Discontinued - Phase-III for Rheumatoid arthritis in Romania (PO) Updated 29 Oct 2013 |
| 29 Oct 2013 | Phase Change - Discontinued(III) | Discontinued - Phase-III for Rheumatoid arthritis in Russia (PO) Updated 29 Oct 2013 |
| 29 Oct 2013 | Phase Change - Discontinued(III) | Discontinued - Phase-III for Rheumatoid arthritis in Serbia (PO) Updated 29 Oct 2013 |
| 29 Oct 2013 | Phase Change - Discontinued(III) | Discontinued - Phase-III for Rheumatoid arthritis in Slovakia (PO) Updated 29 Oct 2013 |
| 29 Oct 2013 | Phase Change - Discontinued(III) | Discontinued - Phase-III for Rheumatoid arthritis in South Africa (PO) Updated 29 Oct 2013 |
| 29 Oct 2013 | Phase Change - Discontinued(III) | Discontinued - Phase-III for Rheumatoid arthritis in Spain (PO) Updated 29 Oct 2013 |
| 29 Oct 2013 | Phase Change - Discontinued(III) | Discontinued - Phase-III for Rheumatoid arthritis in Ukraine (PO) Updated 29 Oct 2013 |
| 29 Oct 2013 | Phase Change - Discontinued(III) | Discontinued - Phase-III for Rheumatoid arthritis in United Kingdom (PO) Updated 29 Oct 2013 |
| 29 Oct 2013 | Phase Change - Discontinued(III) | Discontinued - Phase-III for Rheumatoid arthritis in USA (PO) Updated 29 Oct 2013 |
| 22 Oct 2013 | Trial Update | AstraZeneca terminates a phase II extension trial in Rheumatoid arthritis in USA, Belgium, Bulgaria, Colombia, France, Germany, Italy, Mexico, Peru, Poland and Romania (NCT00805467) Updated 08 Nov 2013 |
| 01 Oct 2013 | Trial Update | AstraZeneca completes a phase II trial for relapsed or refractory Diffuse large B-cell lymphoma in USA and United Kingdom (NCT01499303) Updated 24 Mar 2014 |
| 06 Sep 2013 | Trial Update | AstraZeneca terminates last phase III trials (OSKIRA-4 and OSKIRA-X) in OSKIRA programme in Rheumatoid arthritis in USA, Europe and other territories (NCT01242514, NCT01264770) Updated 16 Sep 2013 |
| 24 Jul 2013 | Trial Update | AstraZeneca terminates the phase II OSKIRA-Asia-1 and OSKIRA-Asia-1x trials in Rheumatoid arthritis in Hong Kong, Japan, South Korea, Taiwan, Thailand and Vietnam (NCT01569074; NCT01640054) Updated 31 Jul 2013 |
| 04 Jun 2013 | Licensing Status | Fostamatinib is no longer licensed to AstraZeneca and all rights have been returned to Rigel Pharmaceuticals [8] Updated 06 Jun 2013 |
| 04 Jun 2013 | Scientific Update | Efficacy & adverse events data from two phase III trials (OSKIRA-2 and OSKIRA-3) in Rheumatoid arthritis released by Rigel [8] Updated 06 Jun 2013 |
| 17 Apr 2013 | Phase Change - No development reported(II) | No development reported - Phase-II for Solid tumours in USA (PO) Updated 17 Apr 2013 |
| 17 Apr 2013 | Phase Change - III | Phase-III clinical trials in Rheumatoid arthritis in Colombia (PO) Updated 17 Apr 2013 |
| 17 Apr 2013 | Phase Change - III | Phase-III clinical trials in Rheumatoid arthritis in Netherlands (PO) Updated 17 Apr 2013 |
| 17 Apr 2013 | Trial Update | AstraZeneca completed a phase I trial in healthy volunteers in the US (NCT01645085) Updated 17 Apr 2013 |
| 12 Apr 2013 | Phase Change - Discontinued(II) | Discontinued - Phase-II for T-cell lymphoma in Canada (PO) Updated 12 Apr 2013 |
| 12 Apr 2013 | Phase Change - Discontinued(II) | Discontinued - Phase-II for T-cell lymphoma in USA (PO) Updated 12 Apr 2013 |
| 12 Apr 2013 | Phase Change - Discontinued(Preclinical) | Discontinued - Preclinical for Chronic lymphocytic leukaemia in USA (PO) Updated 12 Apr 2013 |
| 12 Apr 2013 | Phase Change - Discontinued(Preclinical) | Discontinued - Preclinical for Type-1 diabetes mellitus in USA (PO) Updated 12 Apr 2013 |
| 05 Apr 2013 | Scientific Update | Top-line efficacy and adverse events data from a phase III Oskira-1 trial in Rheumatoid arthritis released by AstraZeneca (NCT01197521) [126] Updated 10 Apr 2013 |
| 28 Feb 2013 | Trial Update | AstraZeneca completes a phase III Oskira-3 trial in Rheumatoid arthritis in the USA, Argentina, Belgium, Brazil, Canada, France, Germany, Hungary, Israel, Italy, Mexico, Portugal, South Africa, Spain and the UK (NCT01197755) Updated 08 Apr 2013 |
| 31 Jan 2013 | Trial Update | AstraZeneca completes the Oskira ABPM trial in Rheumatoid arthrits in USA, Europe (Bulgaria, Czech Republic, Germany, Poland and Ukraine) and South Africa (NCT01563978) Updated 08 Apr 2013 |
| 14 Dec 2012 | Phase Change - II | Phase-II clinical trials in Rheumatoid arthritis in Vietnam (PO) Updated 08 Apr 2013 |
| 14 Dec 2012 | Scientific Update | Top-line efficacy data from a phase IIb trial in Rheumatoid arthritis released by AstraZeneca [125] Updated 18 Dec 2012 |
| 01 Dec 2012 | Trial Update | AstraZeneca completes a Phase-I drug interaction trial in healthy volunteers in USA (NCT01682408) Updated 18 Jan 2013 |
| 30 Nov 2012 | Trial Update | AstraZeneca completes a phase III Oskira-1 trial in Rheumatoid arthritis in the USA, Argentina, Australia, Belgium, Brazil, Bulgaria, Chile, Estonia, France, Hungary, India, Mexico, Peru, Poland, Slovakia, Ukraine and the UK (NCT01197521) Updated 08 Apr 2013 |
| 29 Aug 2012 | Trial Update | AstraZeneca completes a phase I trial in volunteers in United Kingdom (NCT01598571) Updated 29 Aug 2012 |
| 21 Aug 2012 | Trial Update | AstraZeneca completes enrolment in a phase I pharmacokinetic trial in healthy Japanese volunteers (NCT01608542) Updated 28 Aug 2012 |
| 10 Aug 2012 | Trial Update | AstraZeneca completes enrolment in the phase III OSKIRA-3 trial for Rheumatoid arthritis in Argentina, Australia, Belgium, Brazil, Canada, Czech Republic, England, France, Germany, Hungary, Israel, Italy, Mexico, Portugal, South Africa, Spain, and USA (NCT01197755) Updated 27 Aug 2012 |
| 09 Aug 2012 | Phase Change - II | Phase-II clinical trials in Rheumatoid arthritis in Hong Kong (PO) Updated 24 Aug 2012 |
| 09 Aug 2012 | Phase Change - II | Phase-II clinical trials in Rheumatoid arthritis in South Korea (PO) Updated 24 Aug 2012 |
| 09 Aug 2012 | Phase Change - II | Phase-II clinical trials in Rheumatoid arthritis in Thailand (PO) Updated 24 Aug 2012 |
| 31 Jul 2012 | Trial Update | AstraZeneca initiates enrolment in a phase I bioequivalence trial in healthy volunteers in USA (NCT01645085) Updated 20 Aug 2012 |
| 30 Jun 2012 | Phase Change - I | Phase-I clinical trials in Rheumatoid arthritis (volunteers) in United Kingdom (PO) Updated 29 Aug 2012 |
| 30 May 2012 | Trial Update | AstraZeneca plans a phase I bioavailability trial in Healthy volunteers in Japan (NCT01608542) Updated 20 Jun 2012 |
| 18 May 2012 | Phase Change - II | Phase-II clinical trials in Rheumatoid arthritis in Japan (PO) Updated 30 May 2012 |
| 18 May 2012 | Phase Change - II | Phase-II clinical trials in Rheumatoid arthritis in Taiwan (PO) Updated 30 May 2012 |
| 18 May 2012 | Trial Update | AstraZeneca initiates enrolment in the OSKIRA-ABPM and OSKIRA-Asia-1 trials for Rheumatoid arthritis (NCT01563978 and NCT01569074) Updated 30 May 2012 |
| 30 Mar 2012 | Trial Update | AstraZeneca completes enrolment in the phase III OSKIRA-2 trial in Canada, Czech Republic, England, Germany, India, Israel, Italy, Latvia, Lithuania, Portugal, Romania, Serbia, South Africa, Spain, Ukraine, and the USA (NCT01197534) Updated 01 Jun 2012 |
| 23 Mar 2012 | Trial Update | AstraZeneca plans two phase II trials for Rheumatoid arthritis (NCT01563978, NCT01569074) Updated 11 Apr 2012 |
| 06 Mar 2012 | Phase Change - No development reported(Preclinical) | No development reported - Preclinical for Chronic lymphocytic leukaemia in USA (PO) Updated 29 Mar 2012 |
| 01 Mar 2012 | Phase Change - No development reported(II) | No development reported - Phase-II for T-cell lymphoma in Canada (PO) Updated 29 Mar 2012 |
| 01 Mar 2012 | Phase Change - No development reported(II) | No development reported - Phase-II for T-cell lymphoma in USA (PO) Updated 29 Mar 2012 |
| 01 Mar 2012 | Phase Change - No development reported(Preclinical) | No development reported - Preclinical for Type-1 diabetes mellitus in USA (PO) Updated 29 Mar 2012 |
| 31 Jan 2012 | Trial Update | Rigel Pharmaceuticals completes a phase II trial in Solid tumours (late-stage disease) in US (NCT00923481) Updated 29 Mar 2012 |
| 25 Jan 2012 | Trial Update | AstraZeneca initiates enrolment in a phase II trial for relapsed or refractory diffuse large B-cell lymphoma in the USA (NCT01499303) Updated 25 Jan 2012 |
| 11 Jan 2012 | Phase Change - III | Phase-III clinical trials in Rheumatoid arthritis in Canada (PO) Updated 27 Aug 2012 |
| 06 Jan 2012 | Trial Update | AstraZeneca and Rigel Pharmaceuticals complete enrolment in the phase III OSKIRA-1 (Oral SYK Inhibition in Rheumatoid Arthritis) trial in the USA (NCT01197521) Updated 06 Jan 2012 |
| 01 Nov 2011 | Trial Update | AstraZeneca completes a phase I trial in Healthy volunteers in United Kingdom (NCT01276262) Updated 02 Mar 2012 |
| 31 Aug 2011 | Trial Update | AstraZeneca completes a phase I trial in Healthy volunteers in USA (NCT01387308) Updated 25 Nov 2011 |
| 16 Aug 2011 | Trial Update | AstraZeneca initiates enrolment in a phase I trial in Healthy volunteers in USA (NCT01387308) Updated 30 Aug 2011 |
| 21 Jul 2011 | Trial Update | AstraZeneca completes a phase I trial in Healthy volunteers in USA (NCT01336218) Updated 04 Aug 2011 |
| 30 Jun 2011 | Trial Update | AstraZeneca completes a phase I trial in healthy volunteers in USA (NCT01167868) Updated 14 Jul 2011 |
| 01 Jun 2011 | Trial Update | AstraZeneca completes a phase I trial in healthy volunteers or subjects with renal impairment in USA (NCT01245790) Updated 06 Jul 2011 |
| 31 May 2011 | Trial Update | AstraZeneca completes a phase I trial in healthy volunteers (in combination with pioglitazone) in USA (NCT01309854) Updated 13 Jul 2011 |
| 31 May 2011 | Trial Update | AstraZeneca completes a phase I trial in Healthy volunteers in United Kingdom (NCT01311622) Updated 06 Jul 2011 |
| 04 May 2011 | Trial Update | AstraZeneca initiates enrolment in a phase I trial in Healthy volunteers in United Kingdom (NCT01336218) Updated 20 May 2011 |
| 29 Apr 2011 | Trial Update | AstraZeneca initiates enrolment in a phase I pharamcokinetic trial (in combination with pioglitazone) in healthy volunteers in USA (NCT01309854) Updated 17 May 2011 |
| 24 Mar 2011 | Trial Update | AstraZeneca initiates enrolment in a phase I trial in Rheumatoid arthritis in healthy volunteers (in combination with warfarin) in UK (NCT01276262) Updated 08 Apr 2011 |
| 24 Mar 2011 | Phase Change - I | Phase-I clinical trials in Rheumatoid arthritis in healthy volunteers in United Kingdom (PO) Updated 05 Apr 2011 |
| 22 Feb 2011 | Phase Change - III | Phase-III clinical trials in Rheumatoid arthritis in Russia (PO) Updated 30 May 2012 |
| 01 Jan 2011 | Trial Update | AstraZeneca initiates enrolment in the Oskira-4 trial for Rheumatoid arthritis in USA and Canada (NCT01264770) Updated 16 Jun 2011 |
| 30 Nov 2010 | Trial Update | AstraZeneca initiates enrolment in a phase I trial for Rheumatoid Arthritis in the US Updated 14 Dec 2010 |
| 20 Oct 2010 | Trial Update | AstraZeneca initiates enrolment in a Phase-I bioavailability trial of different tablet formulations [NCT01208155] in healthy volunteers in USA Updated 04 Nov 2010 |
| 01 Oct 2010 | Trial Update | AstraZeneca completes a phase I/II trial in B-cell lymphoma (Second-line therapy or greater) in USA (NCT00446095) Updated 09 Jan 2015 |
| 01 Oct 2010 | Phase Change - III | Phase-III clinical trials in Rheumatoid arthritis in Argentina (PO) Updated 08 Apr 2013 |
| 01 Oct 2010 | Phase Change - III | Phase-III clinical trials in Rheumatoid arthritis in Belgium (PO) Updated 08 Apr 2013 |
| 01 Oct 2010 | Phase Change - III | Phase-III clinical trials in Rheumatoid arthritis in Brazil (PO) Updated 08 Apr 2013 |
| 01 Oct 2010 | Phase Change - III | Phase-III clinical trials in Rheumatoid arthritis in Bulgaria (PO) Updated 08 Apr 2013 |
| 01 Oct 2010 | Phase Change - III | Phase-III clinical trials in Rheumatoid arthritis in Chile (PO) Updated 08 Apr 2013 |
| 01 Oct 2010 | Phase Change - III | Phase-III clinical trials in Rheumatoid arthritis in Czech Republic (PO) Updated 08 Apr 2013 |
| 01 Oct 2010 | Phase Change - III | Phase-III clinical trials in Rheumatoid arthritis in Estonia (PO) Updated 08 Apr 2013 |
| 01 Oct 2010 | Phase Change - III | Phase-III clinical trials in Rheumatoid arthritis in France (PO) Updated 08 Apr 2013 |
| 01 Oct 2010 | Phase Change - III | Phase-III clinical trials in Rheumatoid arthritis in Germany (PO) Updated 08 Apr 2013 |
| 01 Oct 2010 | Phase Change - III | Phase-III clinical trials in Rheumatoid arthritis in Hungary (PO) Updated 08 Apr 2013 |
| 01 Oct 2010 | Phase Change - III | Phase-III clinical trials in Rheumatoid arthritis in Italy (PO) Updated 08 Apr 2013 |
| 01 Oct 2010 | Phase Change - III | Phase-III clinical trials in Rheumatoid arthritis in Latvia (PO) Updated 08 Apr 2013 |
| 01 Oct 2010 | Phase Change - III | Phase-III clinical trials in Rheumatoid arthritis in Lithuania (PO) Updated 08 Apr 2013 |
| 01 Oct 2010 | Phase Change - III | Phase-III clinical trials in Rheumatoid arthritis in Mexico (PO) Updated 08 Apr 2013 |
| 01 Oct 2010 | Phase Change - III | Phase-III clinical trials in Rheumatoid arthritis in Peru (PO) Updated 08 Apr 2013 |
| 01 Oct 2010 | Phase Change - III | Phase-III clinical trials in Rheumatoid arthritis in Poland (PO) Updated 08 Apr 2013 |
| 01 Oct 2010 | Phase Change - III | Phase-III clinical trials in Rheumatoid arthritis in Portugal (PO) Updated 08 Apr 2013 |
| 01 Oct 2010 | Phase Change - III | Phase-III clinical trials in Rheumatoid arthritis in Romania (PO) Updated 08 Apr 2013 |
| 01 Oct 2010 | Phase Change - III | Phase-III clinical trials in Rheumatoid arthritis in Serbia (PO) Updated 08 Apr 2013 |
| 01 Oct 2010 | Phase Change - III | Phase-III clinical trials in Rheumatoid arthritis in Slovakia (PO) Updated 08 Apr 2013 |
| 01 Oct 2010 | Phase Change - III | Phase-III clinical trials in Rheumatoid arthritis in Spain (PO) Updated 08 Apr 2013 |
| 01 Oct 2010 | Phase Change - III | Phase-III clinical trials in Rheumatoid arthritis in Ukraine (PO) Updated 08 Apr 2013 |
| 01 Oct 2010 | Phase Change - III | Phase-III clinical trials in Rheumatoid arthritis in Australia (PO) Updated 30 May 2012 |
| 01 Oct 2010 | Phase Change - III | Phase-III clinical trials in Rheumatoid arthritis in India (PO) Updated 30 May 2012 |
| 01 Oct 2010 | Phase Change - III | Phase-III clinical trials in Rheumatoid arthritis in Israel (PO) Updated 30 May 2012 |
| 01 Oct 2010 | Phase Change - III | Phase-III clinical trials in Rheumatoid arthritis in South Africa (PO) Updated 30 May 2012 |
| 30 Sep 2010 | Phase Change - III | Phase-III clinical trials in Rheumatoid arthritis in USA (PO) Updated 13 Oct 2010 |
| 30 Sep 2010 | Licensing Status | Milestone payment triggered by AstraZeneca to Rigel [123] Updated 30 Sep 2010 |
| 01 Sep 2010 | Phase Change - III | Phase-III clinical trials in Rheumatoid arthritis in United Kingdom (PO) Updated 17 Apr 2013 |
| 19 Jul 2010 | Trial Update | AstraZeneca initiates enrolment in a phase I trial in Healthy volunteers in USA (NCT01167868) Updated 26 Apr 2011 |
| 12 Jun 2010 | Active Status Review | Fostamatinib is still in preclinical trials for Chronic lymphocytic leukaemia in USA Updated 28 Jun 2010 |
| 20 May 2010 | Phase Change - Discontinued(II) | Discontinued - Phase-II for Systemic lupus erythematosus in USA (PO) Updated 04 Jun 2010 |
| 20 May 2010 | Trial Update | Rigel Pharmaceuticals terminates the phase II trial SOLEIL in Systemic lupus erythematosus in USA Updated 04 Jun 2010 |
| 05 May 2010 | Trial Update | Rigel completes enrolment in a phase II trial (NCT00798096) for T-cell lymphoma in the US and Canada Updated 17 May 2010 |
| 30 Apr 2010 | Trial Update | AstraZeneca completes a phase II trial in T-cell lymphoma in USA & Canada Updated 12 Aug 2010 |
| 29 Mar 2010 | Licensing Status | Licensing agreement with AstraZeneca becomes effective on expiry of waiting period under the Hart-Scott-Rodino Antitrust Improvements Act [9] Updated 31 Mar 2010 |
| 16 Feb 2010 | Licensing Status | Fostamatinib licensed to AstraZeneca worldwide [10] Updated 18 Feb 2010 |
| 08 Dec 2009 | Scientific Update | Pharmacodynamics data from preclinical trials in B-cell lymphoma presented at the 51st Annual Meeting and Exposition of the American Society of Hematology (ASH-2009) [179] Updated 21 Jan 2010 |
| 21 Oct 2009 | Scientific Update | Efficacy data from two phase II trials in Rheumatoid arthritis presented at the 73rd Annual Scientific Meeting of the American College of Rheumatology and the 44th Annual Meeting of the Association of Rheumatology Health Professionals (ACR/ARHP-2009) [180] , [181] Updated 13 Nov 2009 |
| 23 Jul 2009 | Scientific Update | Efficacy & adverse events data from the phase IIb TASKi-3 trial in Rheumatoid arthritis released by Rigel [136] Updated 28 Jul 2009 |
| 09 Jul 2009 | Scientific Update | Efficacy & adverse events data from the phase IIb TASKi-2 trial in Rheumatoid arthritis released by Rigel [133] Updated 13 Jul 2009 |
| 05 Jun 2009 | Phase Change - No development reported(Preclinical) | No development reported - Preclinical for Leukaemia in USA (PO) Updated 05 Jun 2009 |
| 01 Jun 2009 | Phase Change - II | Phase-II clinical trials in Advanced solid tumours in USA (PO) Updated 05 Jun 2009 |
| 13 Mar 2009 | Trial Update | Rigel Pharmaceuticals initiates enrolment in a phase II trial for T-cell lymphoma in USA Updated 17 Mar 2009 |
| 03 Feb 2009 | Scientific Update | Adverse events data from a clinical trial in Healthy volunteers released by Rigel [137] Updated 05 Feb 2009 |
| 09 Dec 2008 | Phase Change - II | Phase-II clinical trials in T-cell lymphoma in Canada (PO) Updated 17 Mar 2009 |
| 09 Dec 2008 | Phase Change - II | Phase-II clinical trials in T-cell lymphoma in USA (PO) Updated 30 Jan 2009 |
| 09 Dec 2008 | Phase Change - Suspended(II) | Suspended - Phase-II for Systemic lupus erythematosus in USA (PO) Updated 30 Jan 2009 |
| 07 Dec 2008 | Scientific Update | Final efficacy and adverse events data from a phase II trial in B-cell lymphoma presented at the 50th Annual Meeting and Exposition of the American Society of Haematology (ASH-2008) [147] , [182] , [183] Updated 09 Dec 2008 |
| 11 Nov 2008 | Trial Update | Rigel completes enrolment in the phase IIb TASKi-2 trial for Rheumatoid arthritis in the US, EU & Latin America Updated 14 Nov 2008 |
| 29 Oct 2008 | Scientific Update | Efficacy & adverse events data from a phase II trial in Rheumatoid arthritis presented at the 72nd Annual Scientific Meeting of the American College of Rheumatology and the 43rd Annual Meeting of the Association of Rheumatology Health Professional (ACR/ARHP-2008) [140] Updated 03 Nov 2008 |
| 30 Sep 2008 | Phase Change - II | Phase-II clinical trials in Systemic lupus erythematosus in USA (PO) Updated 30 Jan 2009 |
| 12 Jun 2008 | Phase Change - II | Phase-IIb clinical trials (TASKI 2 and TASKI 3) in Rheumatoid arthritis in European Union, Latin America and USA (PO) Updated 16 Jun 2008 |
| 01 May 2008 | Scientific Update | Final pharmacodynamics data from a preclinical study in Systemic lupus erythematosus released by Rigel [155] Updated 01 May 2008 |
| 01 Apr 2008 | Phase Change - Preclinical | Preclinical trials in Type-1 diabetes mellitus in USA (PO) Updated 26 Sep 2008 |
| 13 Dec 2007 | Scientific Update | Efficacy and adverse events data from a phase II trial in rheumatoid arthritis released by Rigel Pharmaceuticals [184] Updated 18 Dec 2007 |
| 09 Nov 2007 | Scientific Update | Adverse events and clinical efficacy data from a phase II trial in immune thrombocytopenic purpura presented at the 49th Annual Meeting and Exposition of the American Society of Hematology (ASH-2007) [185] , [186] Updated 15 Nov 2007 |
| 16 Apr 2007 | Phase Change - II | Phase-II clinical trials in Diffuse large B cell lymphoma in United Kingdom (PO) Updated 25 Mar 2014 |
| 16 Apr 2007 | Phase Change - II | Phase-II clinical trials in Lymphoma in USA (PO) Updated 16 Apr 2007 |
| 01 Apr 2007 | Phase Change - I/II | Phase-I/II clinical trials in B-cell lymphoma (Second-line therapy or greater) in USA (PO) (NCT00446095) Updated 09 Jan 2015 |
| 10 Jan 2007 | Phase Change - II | Phase-II clinical trials in Idiopathic thrombocytopenic purpura in USA (PO) Updated 10 Jan 2007 |
| 31 Dec 2006 | Phase Change - Preclinical | Preclinical trials in Systemic lupus erythematosus in USA (PO) Updated 03 Aug 2007 |
| 12 Dec 2006 | Phase Change - Preclinical | Preclinical trials in Leukaemia in USA (PO) Updated 15 Jan 2007 |
| 12 Dec 2006 | Regulatory Status | Rigel files an IND with the US FDA for lymphoma Updated 15 Jan 2007 |
| 12 Dec 2006 | Scientific Update | Pharmacodynamics data from a preclinical trial in leukaemia presented at the 48th Annual Meeting and Exposition of the American Society of Hematology (ASH-2006) [151] Updated 15 Jan 2007 |
| 06 Sep 2006 | Phase Change - II | Phase-II clinical trials in Rheumatoid arthritis in USA (PO) Updated 07 Sep 2006 |
| 28 Feb 2006 | Phase Change - I | Phase-I clinical trials in Idiopathic thrombocytopenic purpura in USA (PO) Updated 28 Sep 2006 |
| 27 Feb 2006 | Phase Change - Preclinical | Preclinical trials in Idiopathic thrombocytopenic purpura in USA (PO) Updated 27 Feb 2006 |
| 13 Jan 2006 | Phase Change - Preclinical | Preclinical trials in Acute myeloid leukaemia in USA (unspecified route) Updated 13 Jan 2006 |
| 14 Dec 2005 | Scientific Update | Pharmacodynamics data from a trial in rheumatoid arthritis presented at the 69th Annual Scientific Meeting of the American College of Rheumatology and the 40th Annual Meeting of the Association of Rheumatology Health Professionals (ACR/ARHP-2005) [187] Updated 14 Dec 2005 |
| 13 Dec 2005 | Scientific Update | Pharmacodynamics data from a preclinical trial in cancer presented at the 47th Annual Meeting and Exposition of the American Society of Hematology (ASH-2005) Updated 13 Jan 2006 |
| 17 Nov 2005 | Trial Update | Rigel Pharmaceuticals has completed a Phase-I trial in Rheumatoid arthritis in the US for R 788 Updated 17 Nov 2005 |
| 06 Jul 2005 | Trial Update | Rigel Pharmaceuticals has initiated enrolment in a Phase-I trial with R 788 for Rheumatoid arthritis in the USA Updated 10 Aug 2005 |
| 15 Jun 2005 | Phase Change - Preclinical | Preclinical trials in Asthma in USA (PO) Updated 10 Aug 2005 |
| 15 Jun 2005 | Scientific Update | Pharmacodynamics data from a preclinical trial in obstructive airways disease presented at the 101st International Conference of the American Thoracic Society (ATS-2005) [188] Updated 15 Jun 2005 |
| 04 Apr 2005 | Trial Update | Rigel Pharmaceuticals has completed a Phase-I trial in Rheumatoid arthritis in the UK for R 406 Updated 04 Apr 2005 |
| 21 Dec 2004 | Phase Change - I | Phase-I clinical trials in Rheumatoid arthritis in United Kingdom (PO) Updated 13 Jan 2005 |
| 31 Oct 2003 | Phase Change - Preclinical | Preclinical trials in Rheumatoid arthritis in USA (PO) Updated 13 Jan 2005 |
References
-
Rigel Reports Second Quarter 2022 Financial Results and Provides Business Update.
Media Release -
Inmagene and Kissei Enter into an Exclusive License Agreement for Fostamatinib in China.
Media Release -
[JW Pharmaceutical] JW Pharmaceutical Corporation signed a License Agreement for Fostamatinib with Kissei Pharmaceutical Co., Ltd., a Japan-based pharmaceutical company.
Media Release -
Rigel Pharmaceuticals Enters Collaboration and License Agreement with Grifols, S.A. to Commercialize Fostamatinib in Europe.
Media Release -
Rigel Reports Fourth Quarter and Full Year 2019 Financial Results and Provides Business Update.
Media Release -
Rigel Secures Credit Facility for Up to $60 Million.
Media Release -
Rigel Pharmaceuticals Enters Collaboration and License Agreement with Kissei Pharmaceutical Co., Ltd. to Develop and Commercialize TAVALISSE(Tm) (fostamatinib disodium hexahydrate) in Japan and other Asian Countries.
Media Release -
Rigel Will Resume Responsibility for Fostamatinib Program.
Media Release -
Rigel Announces Expiry of Waiting Period Under Hart-Scott-Rodino Act for Licensing Agreement With Astrazeneca.
Media Release -
AstraZeneca and Rigel Pharmaceuticals Sign Worldwide License Agreement for Late-Stage Development Product -- Fostamatinib Disodium (R788) -- for the Treatment of Rheumatoid Arthritis (RA).
Media Release -
Rigel Announces Availability of TAVALISSE(TM) (fostamatinib disodium hexahydrate) in the U.S.
Media Release -
Rigel Announces FDA Approval of TAVALISSE(Tm) (fostamatinib disodium hexahydrate) for Chronic Immune Thrombocytopenia (ITP) in Adult Patients.
Media Release -
Rigel Provides Update on FDA Review of Fostamatinib for ITP.
Media Release -
Rigel Announces Tavalisse(T) as Proprietary Name for Fostamatinib in the United States.
Media Release -
Rigel Announces Oral Presentation of TAVALISSE(T) (fostamatinib disodium) Phase 3 Clinical Data at the European Hematology Association 22nd Annual Congress.
Media Release -
FDA Accepts Rigel's New Drug Application for TAVALISSE(T) (fostamatinib disodium) for the Treatment of Chronic ITP.
Media Release -
Rigel Submits New Drug Application to FDA for Fostamatinib in Chronic ITP.
Media Release -
GRIFOLS_SEC filing_Form-20-F_Dec-2022. Internet-Doc 2023;.
Available from: URL: https://www.sec.gov/ix?doc=/Archives/edgar/data/0001438569/000110465923046470/grfs-20221231x20f.htm#Item4INFORMATIONONTHECOMPANY_944862 -
Grifols begins commercializing TAVLESSE(R) in France, Italy and Spain to treat chronic immune thrombocytopenia.
Media Release -
Grifols to launch TAVLESSE(R) in Europe and Turkey to continue reinforcing its commercial strategy and commitment to patients.
Media Release -
Rigel Receives Positive CHMP Opinion for Fostamatinib Disodium Hexahydrate for Adult Patients with Chronic Immune Thrombocytopenia (ITP) in Europe.
Media Release -
Rigel Receives Positive Trend Vote from CHMP for Fostamatinib Disodium Hexahydrate for Adult Patients with Chronic Immune Thrombocytopenia (ITP) in Europe.
Media Release -
Rigel Announces Second Quarter 2019 Financial Results and Provides Business Update.
Media Release -
Rigel Announces First Quarter 2019 Financial Results and Provides Company Update.
Media Release -
Rigel Receives EMA Validation of the Marketing Authorization Application for Fostamatinib Disodium Hexahydrate in Chronic Immune Thrombocytopenia (ITP) in Adult Patients.
Media Release -
Rigel to Present at the 39th Annual J.P. Morgan Healthcare Conference.
Media Release -
Rigel and Medison Announce Health Canada Approval of TAVALISSE(Rm), an Oral Medication for the Treatment of Adults with Chronic Immune Thrombocytopenia.
Media Release -
Kissei Launches TAVALISSE(Rm) Tab. 100mg and 150mg, an Oral Spleen Tyrosine Kinase Inhibitor, in Japan for Chronic ITP.
Media Release -
Marketing Authorization Approval in Japan for TAVALISSE(R) Tab. 100mg and 150mg, an Oral Spleen Tyrosine Kinase Inhibitor.
Media Release -
Submission of New Drug Application for Fostamatinib, an oral spleen tyrosine kinase inhibitor, in Japan.
Media Release -
Grifols' TAVLESSE(Rm) (fostamatinib) receives NICE recommendation for treating refractory chronic immune thrombocytopenia.
Media Release -
SECURITIES AND EXCHANGE COMMISSION. Internet-Doc 2023;.
Available from: URL: https://www.sec.gov/ix?doc=/Archives/edgar/data/1034842/000155837023003035/rigl-20221231x10k.htm -
Knight Therapeutics annual report 2022. Internet-Doc 2023;.
Available from: URL: https://knighttx.com/Investors-Content/Financial_reports/2022/Knight-AnnualReport2022-upd.pdf -
Knight Therapeutics Reports Second Quarter 2023 Results.
Media Release -
Rigel Granted Orphan Drug Designation for Fostamatinib in ITP.
Media Release -
A Phase III Study in Patients With Chronic Idiopathic Thrombocytopenic Purpura in R788
ctiprofile -
Fostamatinib Meets Primary Endpoint in Phase 3 Trial in Japan for Treatment of Chronic Immune Thrombocytopenia.
Media Release -
Kuwana M, Ito T, Kowata S, Hatta Y, Fujimaki K, Naito K, et al. Long-Term Treatment with Fostamatinib in Japanese Patients with Primary Immune Thrombocytopenia: An Open-Label Extension Study Following a Phase 3 Placebo-Controlled, Double-Blind, Parallel-Group Study. ASH-Hem-2023 2023; abstr. 2578.
Available from: URL: https://ash.confex.com/ash/2023/webprogram/Paper182113.html -
A Phase 3 Open Label Extension Study of Fostamatinib Disodium in the Treatment of Warm Antibody Autoimmune Hemolytic Anemia
ctiprofile -
Rigel Reports First Quarter 2021 Financial Results and Provides Business Update.
Media Release -
Rigel's fostamatinib Enters Phase 3 Clinical Trial in Japan with Kissei Pharmaceuticals for the Treatment of Chronic Immune Thrombocytopenia.
Media Release -
Rigel Pharmaceuticals Provides Business Update.
Media Release -
Expanded Access (Compassionate Use) of Fostamatinib in Patients With Persistent or Chronic Relapsing/Refractory Immune Thrombocytopenic Purpura (ITP)
ctiprofile -
Rigel Announces Fourth Quarter 2016 and Year End 2016 Financial Results and Provides Company Update.
Media Release -
Fostamatinib Study Results Continue to Trend Positive.
Media Release -
Rigel's Fostamatinib Meets Primary Endpoint in Phase 3 Study in Chronic ITP.
Media Release -
Rigel Initiates Phase 3 Studies of Fostamatinib in ITP.
Media Release -
Rigel Announces Webcast of Investor Day on May 6, 2014.
Media Release -
Rigel Provides Pipeline Update.
Media Release -
A Phase 3, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Study of Fostamatinib Disodium in the Treatment of Persistent/Chronic Immune Thrombocytopenic Purpura
ctiprofile -
A Phase 3, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Study of Fostamatinib Disodium in the Treatment of Persistent/Chronic Immune Thrombocytopenic Purpura
ctiprofile -
Rigel Announces Results from the Second FIT Phase 3 Study and the Long-Term Open-Label Extension Study for Fostamatinib in ITP.
Media Release -
Rigel Completes Enrollment of FIT Phase 3 Program for Fostamatinib in ITP.
Media Release -
Rigel Completes Enrollment of First Phase 3 Study of Fostamatinib in ITP (FIT).
Media Release -
Duliege A-M, Arnold DM, Boccia R, Boxer M, Cooper N, Hill QA, et al. Two-Year Safety and Efficacy Outcomes with Fostamatinib in Adult Patients with Immune Thrombocytopenia (ITP): Open-Label Extension to Phase 3 Trial Program. ASH-Hem-2018 2018; abstr. 736.
Available from: URL: https://ash.confex.com/ash/2018/webprogram/Paper110482.html -
A Phase 3 Open Label Extension Study of Fostamatinib Disodium in the Treatment of Persistent/Chronic Immune Thrombocytopenic Purpura
ctiprofile -
Rigel Announces Initiation of Phase II Study Evaluating R788 in Immune Thrombocytopenic Purpura (ITP).
Media Release -
Rigel Announces Third Quarter 2006 Financial Results.
Media Release -
A Phase II, Open-Label, Efficacy and Safety, Ascending Dose, Pilot Study of be Fostamatinib Disodium/R935788 for the Treatment of Adult Refractory Immune Thrombocytopenic Purpura
ctiprofile -
Rigel Provides Update on Plans for sNDA for wAIHA Program Following FDA Feedback.
Media Release -
A Phase 3, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Study of Fostamatinib Disodium in the Treatment of Warm Antibody Autoimmune Hemolytic Anemia
ctiprofile -
Rigel Reports Third Quarter 2021 Financial Results and Provides Business Update.
Media Release -
Cooper N, Numerof RP, Tong S, Kuter DJ. Fostamatinib for the Treatment of Warm Antibody Autoimmune Hemolytic Anemia (wAIHA): A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Global Study. ASH-Hem-2020 2020; abstr. 752.
Available from: URL: https://ash.confex.com/ash/2020/webprogram/Paper140469.html -
Rigel Finalizes the Study Design of its Ongoing Phase 3 Clinical Trial of Fostamatinib in Warm Autoimmune Hemolytic Anemia.
Media Release -
Rigel Reports Third Quarter 2020 Financial Results and Provides Business Update.
Media Release -
Rigel Reports First Quarter 2020 Financial Results and Provides Business Update.
Media Release -
Rigel Pharmaceuticals Provides Business Update 13 Jan 2020.
Media Release -
Rigel Enrolls First Patient in Phase 3 Clinical Trial of Fostamatinib Disodium Hexahydrate in Warm Autoimmune Hemolytic Anemia.
Media Release -
Rigel Reports Second Quarter 2021 Financial Results and Provides Business Update.
Media Release -
Rigel Announces Top-line Results from FORWARD Phase 3 Clinical Trial of Fostamatinib in Patients with Warm Autoimmune Hemolytic Anemia.
Media Release -
Kuter DJ, Piatek CI, Saikali K, Dummer W. Phase 3, Randomized, Double-Blind, Placebo-Controlled, Global Study (FORWARD) of Fostamatinib for the Treatment of Warm Antibody Autoimmune Hemolytic Anemia . ASH-Hem-2022 2022; abstr. 1011.
Available from: URL: https://ash.confex.com/ash/2022/webprogram/Paper169652.html -
Rigel Announces Fourth Quarter and Year End 2017 Financial Results and Provides Company Update.
Media Release -
Rigel To Present Phase 2 Results for Fostamatinib in Autoimmune Hemolytic Anemia at EHA.
Media Release -
A Phase 2, Multi-Center, Open Label, Simon Two-Stage Study to Evaluate the Safety and Efficacy of Fostamatinib Disodium in the Treatment of Warm Antibody Autoimmune Hemolytic Anemia
ctiprofile -
Rigel Announces Third Quarter 2017 Financial Results and Provides Company Update.
Media Release -
Fostamatinib Meets Pre-Specified Primary Endpoint in Stage 1 of Autoimmune Hemolytic Anemia (AIHA) Phase 2 Study.
Media Release -
Rigel Announces First Quarter 2017 Financial Results and Provides Company Update.
Media Release -
Rigel Provides Business Updates and Preliminary Data in IgA Nephropathy.
Media Release -
Rigel Announces Fourth Quarter and Year End 2015 Financial Results.
Media Release -
Rigel Initiates Phase 2 Clinical Trial Of Fostamatinib In Autoimmune Hemolytic Anemia.
Media Release -
Rigel Reviews Recent Progress and Announces Presentation at the 34th Annual J.P. Morgan Healthcare Conference in San Francisco.
Media Release -
Rigel Announces Second Quarter 2017 Financial Results and Provides Company Update.
Media Release -
Rigel to Provide Business Review and Updated Phase 2 Results for Fostamatinib in AIHA at the 36th Annual J.P. Morgan Healthcare Conference.
Media Release -
Rigel Announces Upcoming Data Presentations at the 61st ASH Annual Meeting & Exposition.
Media Release -
Kuter D, Richy A, Boxer M, Broome C, Arnold D, Field J, et al. Fostamatinib, a Spleen Tyrosine Kinase Inhibitor, for the Treatment of Warm Antibody Autoimmune Hemolytic Anemia: Initial Results of the Open-Label Extension Period of the Soar Phase 2 Study. EHA-2019 2019; abstr. PF427.
Available from: URL: https://library.ehaweb.org/eha/2019/24th/266227/david.kuter.fostamatinib.a.spleen.tyrosine.kinase.inhibitor.for.the.treatment.html?f=listing%3D3%2Abrowseby%3D8%2Asortby%3D2%2Amedia%3D3%2Ace_id%3D1550 -
Kuter DJ, Agajanian R, Arnold DM, Boxer M, Broome C, Field JJ, et al. Fostamatinib, a Spleen Tyrosine Kinase Inhibitor, for the Treatment of Warm Antibody Autoimmune Hemolytic Anemia: Initial Results of the Multicenter, Open-Label Extension Period of the Soar Phase 2 Study. ASH-Hem-2018 2018; abstr. 3612.
Available from: URL: https://ash.confex.com/ash/2018/webprogram/Paper110483.html -
Rogers KA, Boxer MA, Choi MY, Agajanian R, Arnold DM, Broome CM, et al. Fostamatinib, a Spleen Tyrosine Kinase (SYK) Inhibitor, for the Treatment of Warm Antibody Autoimmune Hemolytic Anemia (wAIHA): Final Results of the Phase 2, Multicenter, Open-Label Study. ASH-Hem-2019 2019; abstr. 3518.
Available from: URL: https://ash.confex.com/ash/2019/webprogram/Paper126509.html -
Rigel Announces Publication of Data from Phase 2 Clinical Study of Fostamatinib for the Treatment of Warm Antibody Autoimmune Hemolytic Anemia in the American Journal of Hematology.
Media Release -
RIGEL PHARMACEUTICALS_10-K_SEC-filing_Dec-2023. Internet-Doc 2024;.
Available from: URL: https://www.sec.gov/ixviewer/ix.html?doc=/Archives/edgar/data/1034842/000155837024002475/rigl-20231231x10k.htm -
Rigel Pharmaceuticals Provides Update on COVID-19 Program.
Media Release -
Fostamatinib Selected for NIH ACTIV-4 COVID-19 Clinical Trial.
Media Release -
Rigel Reports Third Quarter 2023 Financial Results and Provides Business Update.
Media Release -
CONNECTS Master Protocol for Clinical Trials Targeting Macro-, Micro-immuno-thrombosis, Vascular Hyperinflammation, and Hypercoagulability and Renin-angiotensin-aldosterone System (RAAS) in Hospitalized Patients With COVID-19 (ACTIV-4 Host Tissue)
ctiprofile -
Rigel Awarded $16.5 Million from U.S. Department of Defense for Phase 3 Clinical Trial of Fostamatinib in COVID-19 Patients.
Media Release -
Double-Blind, Randomized, Placebo-Controlled, Multi-Center Phase 3 Study to Evaluate the Efficacy and Safety of Fostamatinib in COVID-19 Subjects
ctiprofile -
Mallat Z, Lobo SM, Malik A, Tong S. Phase 3 Trial of Fostamatinib for the Treatment of COVID-19: Repurposing an Immunomodulatory Drug Previously Approved for Immune Thrombocytopenia. IDW-2021 2021; abstr. 561.
Available from: URL: https://academic.oup.com/ofid/article/8/Supplement_1/S382/6450226 -
Rigel Pharmaceuticals and Forma Therapeutics Announce Licensing Agreement for Olutasidenib, a Novel Mutant IDH1 Inhibitor for the Potential Treatment of Relapsed or Refractory Acute Myeloid Leukemia.
Media Release -
Rigel Reports First Quarter 2022 Financial Results and Provides Business Update.
Media Release -
Rigel Announces Top-line Results from FOCUS Phase 3 Clinical Trial of Fostamatinib in High Risk Hospitalized COVID-19 Patients.
Media Release -
Rigel Announces Presentation at the Upcoming IDWeek 2023.
Media Release -
Gotur DB, Malik A, Markovtsov V, Yan L, Dummer W, Mallat Z. Fostamatinib for the Treatment of Hospitalized Patients With COVID-19 Who Required Oxygen Supplementation: Results of a Phase 3 Trial. IDW-2023 2023; abstr. 88.
Available from: URL: https://academic.oup.com/ofid/article/10/Supplement_2/ofad500.004/7448311 -
Positive Topline Data Shows Fostamatinib Meets Primary Endpoint of Safety in Phase 2 Clinical Trial in Hospitalized Patients with COVID-19.
Media Release -
Rigel Announces Completion of Patient Enrollment for NIH/NHLBI-Sponsored Phase 2 Trial of Fostamatinib in Hospitalized COVID-19 Patients.
Media Release -
Rigel Announces NIH/NHLBI-Sponsored Trial of Fostamatinib in Hospitalized COVID-19 Patients in Collaboration with Inova.
Media Release -
A Phase II Study Evaluating Fostamatinib for Hospitalized Adults With COVID-19
ctiprofile -
Data from NIH/NHLBI-Sponsored Phase 2 Trial of Fostamatinib in Hospitalized COVID-19 Patients Published in Clinical Infectious Diseases.
Media Release -
Phase 2/3, Randomised, Open-Label, Single-Site, Multi-Arm Trial of Ruxolitinib Plus Best Supportive Treatment (BST) versus Fostamatinib Plus BST versus BST for COVID-19 pneumonia
ctiprofile -
Rigel Announces Investigator-Sponsored Trial of Fostamatinib in Patients with COVID-19 Pneumonia.
Media Release -
Rigel Reports Second Quarter 2020 Financial Results, Provides Business Update, and Overviews COVID-19 Program.
Media Release -
Gaillard S, Wilkinson M, Martin LP, Deery A, Langsdale A, Bayable A, et al. A phase 1 study of the SYK inhibitor fostamatinib and weekly paclitaxel for recurrent platinum-resistant ovarian cancer. ASCO-2023 2023; abstr. 5574.
Available from: URL: https://meetings.asco.org/abstracts-presentations/223056 -
Phase I Clinical Trial of Combined Fostamatinib and Paclitaxel in Ovarian Cancer
ctiprofile -
Markovtsov V, Masuda E. SYK inhibition with fostamatinib in Waldenstrom's macroglobulinemia: In vitro cell based assays. ASCO-2019 2019; abstr. e19047.
Available from: URL: http://abstracts.asco.org/239/AbstView_239_264441.html -
Rigel Announces Topline Data from Proof-of-Concept Phase 2 Study of Fostamatinib in IgA Nephropathy.
Media Release -
Rigel Announces Third Quarter 2014 Financial Results.
Media Release -
R348 Did Not Meet Endpoints in Phase 2 Dry Eye Study.
Media Release -
Rigel to Present at the 33rd Annual J.P. Morgan Healthcare Conference.
Media Release -
A Phase 2, Multi-Center, Randomised, Double-Blind, Ascending-Dose, Placebo-Controlled Clinical Study to Assess the Safety and Efficacy of Fostamatinib in the Treatment of IgA Nephropathy
ctiprofile -
A Phase 2, Multi-Centre, Open Label Extension Study of Fostamatinib in the Treatment of IgA Nephropathy for Patients Who Participated in Study C-935788-050
ctiprofile -
AstraZeneca initiates phase III clinical development of fostamatinib for the treatment of rheumatoid arthritis.
Media Release -
Rigel Announces Initiation of Clinical Trials in Two Immunology Programs.
Media Release -
(OSKIRA-X): A Long-term Extension Study to Assess the Safety and Efficacy of Fostamatinib Disodium in the Treatment of Rheumatoid Arthritis
ctiprofile -
Rigel Announces Third Quarter 2012 Financial Results.
Media Release -
Rigel Earns Milestone Payments From AstraZeneca.
Media Release -
Data Published Today Reveal That Novel Oral Therapy Fostamatinib Demonstrates Positive Response in Rheumatoid Arthritis Patients.
Media Release -
AstraZeneca Announces Top-Line Results of OSKIRA-4 Phase IIb Study of Fostamatinib as a Monotherapy for Rheumatoid Arthritis.
Media Release -
AstraZeneca Announces Top-Line Results From OSKIRA-1 Phase 3 Study of Fostamatinib in Rheumatoid Arthritis.
Media Release -
(OSKIRA-1): A Phase III, Multi-centre, Randomised, Double-Blind, Placebo-Controlled, Parallel Group Study of Two Dosing Regimens of Fostamatinib Disodium in Rheumatoid Arthritis Patients With an Inadequate Response to Methotrexate.
ctiprofile -
(OSKIRA-2): A Phase III, Multi-centre, Randomised, Double-Blind, Placebo-Controlled, Parallel Group Study of Two Dosing Regimens of Fostamatinib Disodium in Rheumatoid Arthritis Patients With an Inadequate Response to DMARDs.
ctiprofile -
(OSKIRA-3): A Phase III, Multi-centre, Randomised, Double-Blind, Placebo-Controlled, Parallel Group Study of Two Dosing Regimens of Fostamatinib Disodium in Rheumatoid Arthritis Patients With Inadequate Response to a TNF-alpha Antagonist.
ctiprofile -
OSKIRA-ABPM: A Multi-Centre, Randomised, Double-Blind, Placebo-Controlled, Parallel Group Study of the Effect of Fostamatinib 100 mg Twice Daily on 24-hour Ambulatory Blood Pressure in Patients With Rheumatoid Arthritis.
ctiprofile -
(OSKIRA-Asia-1): A Multi-centre, Randomised, Double-Blind, Placebo-Controlled, Parallel Group Dose Ranging Study in Asia Evaluating Efficacy and Safety of Fostamatinib in Patients With Active Rheumatoid Arthritis Who Are Inadequate Responders to Methotrexate Therapy.
ctiprofile -
(OSKIRA-Asia-1X): A Long-term Study to Assess the Safety of Fostamatinib in the Treatment of Rheumatoid Arthritis in Asia [EXTENSION OF 700215781]
ctiprofile -
Rigel's R788 Significantly Improves Rheumatoid Arthritis in Phase 2b Clinical Trial.
Media Release -
A phase II, multicenter, randomized, double-blind, placebo-controlled, parallel dose study of two doses of R935788 [R 788, fostamatinib] in rheumatoid arthritis patients failing to respond to methotrexate.
ctiprofile -
A Phase II, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Dose Study of R935788 [R 788, fostamatinib] in Patients With Rheumatoid Arthritis Who Have Failed at Least One Biologic
ctiprofile -
R788 in TASKi3 Clinical Trial Does Not Meet Efficacy Endpoints in RA Patients Who Had Previously Failed Biologic Therapies - Results Incongruent.
Media Release -
Rigel Expects R788 Partnership After Phase 2b Clinical Trials Results.
Media Release -
Rigel's R788 Phase 2a Results Published in Arthritis and Rheumatism.
Media Release -
Rigel Initiates Two Phase 2b Clinical Trials of R788 in Rheumatoid Arthritis.
Media Release -
Weinblatt ME, Kavanaugh A, Grossbard E, TASKI-1 Trial. Treatment of rheumatoid arthritis with a Syk kinase inhibitor: a 12 week randomized placebo controlled study. 72nd-ACR-43rd-ARHP-2008 2008; abstr. 1189.
Available from: URL: http://www.rheumatology.org/annual/index.asp -
Rigel Announces Initiation of Phase II Study Evaluating R788 in Rheumatoid Arthritis.
Media Release -
Rigel Provides Clinical Update of R788 Phase 2 Trials in ITP, Rheumatoid Arthritis and Lymphoma.
Media Release -
A phase II, multicenter, randomized, double-blind, placebo-controlled, ascending dose, dose ranging study to evaluate up to three doses of R935788 [R-788, fostamatinib; Rigel] in rheumatoid arthritis patients failing to respond to methotrexate.
ctiprofile -
An Open-Label, Multicenter Extension Study to Evaluate the Safety of R935788 in Patients With Rheumatoid Arthritis Who Have Completed the Treatment Phase of a Rigel-Sponsored R935788 Study.
ctiprofile -
Rigel Advances Clinical Development Programs for R788 and R763.
Media Release -
Rigel Announces Second Quarter 2006 Financial Results.
Media Release -
Phase 2 Results of Rigel's R788 Show Clinical Benefit in Diffuse Large B-Cell Lymphoma and CLL.
Media Release -
A Randomised Double Blind Phase II Trial to Evaluate the Efficacy of Two Doses of Fostamatinib in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL)
ctiprofile -
A Phase I/II Multi-Center, Open Label Trial of the Safety and Efficacy of Fostamatinib in Patients With Relapsed/Refractory B-Cell Lymphoma.
ctiprofile -
Hoellenriegel J, Coffey G, Sinha U, Pandey A, Wierda W, Keating M, et al. Selective Inhibitors of the Spleen Tyrosine Kinase (Syk) Block Cell Survival and Migration in Chronic Lymphocytic Leukemia. 15th-EHA-2010 2010; abstr. 0542.
Available from: URL: http://eha.eurocongres.com/15th -
Rigel's R788 Shows Promise for Treating B-Cell Lymphoma and Leukemia in Preclinical Studies.
Media Release -
A Broad Multi-Histology Phase II Study of the Multi-Kinase Inhibitor R935788 (Fostamatinib Disodium) in Advanced Colorectal, Non-Small Cell Lung, Head and Neck, Hepatocellular and Renal Cell Carcinomas and Pheochromocytoma and Thyroid Tumors.
ctiprofile -
Rigel's R788 Evaluated in Phase 2 Trial in Multiple Cancers.
Media Release -
A Phase II, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Dose Study of R935788 in Systemic Lupus Erythematosus Patients With Active Disease.
ctiprofile -
Rigel's R788 Slows Progression of Murine Lupus in Preclinical Studies.
Media Release -
Rigel Commences Phase 2 Trial of R788 in Peripheral T-Cell Lymphomas.
Media Release -
Phase II, Multicenter, Simon Two-Stage Study of R788 in Patients With Relapsed or Refractory T-Cell Lymphoma.
ctiprofile -
Rigel Announces Second Quarter 2008 Financial Results.
Media Release -
An Open-label, Single-center, Randomized, 4-way Crossover Study to Assess the Bioequivalence of R406 in Healthy Volunteers When 100 and 150mg of Fostamatinib Are Administered as the 13% Drug-loaded Tablet Versus the 38% Drug-loaded Tablet
ctiprofile -
An Open-Label, Non-Randomized, 2-Period, Single Center Study to Assess the Single Dose Pharmacokinetics of R406 in Healthy Subjects When Fostamatinib 150 mg is Administered Alone and in Combination With Rifampicin.
ctiprofile -
An Open-Label, Single Center Study to Assess the Pharmacokinetics of Pioglitazone in Healthy Subjects When Administered Alone and in Combination With Fostamatinib 100 mg Twice Daily.
ctiprofile -
An Open-label, Single-center, 2-Part, Randomized Study to Assess the Pharmacokinetics of R406 in Healthy Subjects When Fostamatinib 150 mg is Administered Alone in Fed and Fasted State and in Combination With Ranitidine in Fasted State, and to Assess the Relative Bioavailability of Process Variants of Tablets
ctiprofile -
An Open-Label, Single Centre Study to Assess the Pharmacokinetics and Pharmacodynamics of Warfarin When Co-Administered With Fostamatinib in Healthy Subjects.
ctiprofile -
An Open-Label, Non-Randomised, 2-Period, Single Centre Study to Assess the Pharmacokinetics of Digoxin in Healthy Subjects When Administered Alone and in Combination With Fostamatinib 100 mg Twice Daily.
ctiprofile -
An Open-label, Non-randomized, 2-Period, Fixed Sequence, Single-center Study to Assess the Pharmacokinetics of Rosuvastatin and Simvastatin in Healthy Subjects When Administered Alone and in Combination With Fostamatinib 100 mg Twice Daily
ctiprofile -
A Single-blind, Placebo-controlled, 2-period, Fixed Sequence Study to Determine the Effects of Coadministration of Fostamatinib 100 mg Twice Daily on the Pharmacokinetics of an Oral Contraceptive in Healthy Female Subjects.
ctiprofile -
A Phase I, Open-label Study to Assess the Pharmacokinetics of Oral Fostamatinib in Healthy Japanese Subjects After Single and Multiple Doses
ctiprofile -
A Phase I, Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Assess the Safety, Tolerability and Pharmacokinetics of Oral Fostamatinib Disodium in Healthy Japanese and White Subjects After Single and Multiple Ascending Doses.
ctiprofile -
An Open-label, Phase I Study to Assess the Pharmacokinetics of R406 in Subjects With Renal Impairment Compared to Healthy Subjects Following Administration of a Single Dose of Fostamatinib 150 mg.
ctiprofile -
An Open-label, Randomized, Four-way Crossover Study in Healthy Male Subjects to Assess the Relative Bioavailability of 4 Different Fostamatinib Tablets3.
ctiprofile -
An Open-label, Partially Randomized, 5-way Crossover Study in Healthy Volunteers to Assess the Relative Bioavailability of 100 and 150 mg Fostamatinib Tablets Compared With 50 mg Fostamatinib Tablets.
ctiprofile -
A Study to Assess the Absolute Bioavailability of a Single Oral Dose of Fostamatinib With Respect to an Intravenous Micro Tracer Dose of [14C] R406 in Healthy Male Volunteers
ctiprofile -
A Phase I Trial of Fostamatinib and Chronic Graft vs. Host Disease Development After Allogeneic Stem Cell Transplantation
ctiprofile -
RIGEL PHARMACEUTICALS 10-K. Internet-Doc 2021;.
Available from: URL: https://www.sec.gov/ix?doc=/Archives/edgar/data/1034842/000155837021002254/rigl-20201231x10k.htm -
Grifols starts commercializing TAVLESSE(Rm) in Europe, diversifying its medicines portfolio.
Media Release -
Arkenau H-T, Patrikidou A, Flinn I, Hylton JC, Tong S, Ardeshna K. Fostamatinib for the treatment of diffuse large B-cell lymphoma. ASCO-2020 2020; abstr. e20067.
Available from: URL: https://meetinglibrary.asco.org/record/190269/abstract -
Markovtsov VV, Yi S, Young C, Duliege A-M. Prediction of Response to Fostamatinib Based on the Presence of Plasma Platelet Autoantibodies in Adult Patients with Immune Thrombocytopenia (ITP) - Exploratory Analyses from Phase 3 Studies. ASH-Hem-2018 2018; abstr. 3766.
Available from: URL: https://ash.confex.com/ash/2018/webprogram/Paper113705.html -
Rigel Announces Third Quarter 2018 Financial Results and Provides Company Update.
Media Release -
Rossi RM, Grose V, Pine P, Fisher RI, Jordan CT, Friedberg JW. Rational Combinations Including a Novel Syk Inhibitor, Fostamatinib Disodium (FosD) in Diffuse Large B Cell Lymphoma. 51st-ASH-2009 2009; abstr. 283.
Available from: URL: http://www.hematology.org -
Weinblatt M, Kavanaugh A, Genovese M, Grossbard E, Magilavy D. Treatment of Rheumatoid Arthritis (RA) with An Oral Syk Kinase Inhibitor: A 6 Month Randomized Placebo Controlled Phase 2b Study in Patients with Active RA On Chronic Methotrexate. 73rd-ACR-44th-ARHP-2009 2009; abstr. LB2.
Available from: URL: http://www.rheumatology.org -
Genovese M, Kavanaugh A, Peterfy C, Magilavy D. An oral syk kinase inhibitor in the treatment of rheumatoid arthritis(RA): A 3 month randomized placebo controlled phase 2 study in patients with active RA who had failed biologic agents. 73rd-ACR-44th-ARHP-2009 2009; abstr. LB3.
Available from: URL: http://www.rheumatology.org -
Novel Treatments Demonstrate Improvements in Overall Survival and Response Rates in Difficult-To-Treat Forms of Leukemia and Lymphoma.
Media Release -
Friedberg JW, Sharman J, Schaefer-Cutillo J, Johnston PB, de Vos S, LaCasce A, et al. Fostamatinib disodium, an oral inhibitor of Syk, is well-tolerated and has significant clinical activity in diffuse large B cell lymphoma and chronic lymphocytic leukemia. 50th-ASH-2008 2008; abstr. 3.
Available from: URL: http://www.hematology.org -
Rigel's R788 Demonstrates Significant Improvement in Rheumatoid Arthritis in Phase 2 Clinical Study.
Media Release -
Rigel R788 Raises Platelet Counts in Immune Thrombocytopenic Purpura (ITP) Patients in Phase 2 Study.
Media Release -
Bussel JB, Schindler AM, Grossbard EB. R935788: a phase II, single center, open label, efficacy and safety, ascendng dose, pilot study for the treatment of adult immune thrmbocytopenic purpura. Blood 2007;110(11):394-395.
-
Grossbard E, Mant T, Jurcevic S, Sterba M. An orally bioavailable inhibitor of Syk kinase (R406) inhibits, dose responsively, human basophil CD63 expression following ex vivo F-epsilon receptor stimulation. Arthritis-Rheum 2005;52 (Suppl.)(9):568.
-
Matsubara S, Takeda K, Li G, Koya T, Miyahara N, et al. Inhibitory action of a specific syk kinase inhibitor on allergen-induced airway hyperresponsiveness and inflammation in mice. Proc-Am-Thoracic-Soc 2005;2 (Abstr. Suppl.)754.
-
Rigel Announces First Quarter 2018 Financial Results and Provides Company Update.
Media Release -
Rigel Announces Presentation of Phase I Data on R406/788 at the American College of Rheumatology (ACR) Annual Meeting.
Media Release
Adis International Ltd. Part of Springer Science+Business Media
© Springer Nature Switzerland AG