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Roxadustat - FibroGen

Drug Profile

Roxadustat - FibroGen

Alternative Names: ASP 1517; AZD 9941; EVRENZO; Evrenzo; FG-4592

Latest Information Update: 28 Feb 2024

At a glance

  • Originator FibroGen
  • Developer Astellas Pharma; AstraZeneca; FibroGen
  • Class Amides; Antianaemics; Carboxylic acids; Isoquinolines; Small molecules
  • Mechanism of Action Hypoxia-inducible factor-proline dioxygenase inhibitors
  • Orphan Drug Status

    Orphan designation is assigned by a regulatory body to encourage companies to develop drugs for rare diseases.

    No
  • New Molecular Entity Yes

Highest Development Phases

  • Marketed Anaemia
  • Preregistration Chemotherapy-induced anaemia
  • Discontinued Sickle cell anaemia

Most Recent Events

  • 26 Feb 2024 FibroGen and AstraZeneca terminates the license agreement for Roxadustat from AstraZeneca in the United States and other AstraZeneca territories, excluding China and South Korea
  • 09 Dec 2023 Efficacy and adverse events data from a phase III MATTERHORN trial in Anaemia presented at the 65th American Society of Hematology Annual Meeting and Exposition (ASH-Hem-2023)
  • 20 Nov 2023 Phase-III clinical trials in Anaemia (In infants, In children, In adolescents) in Romania (PO) (NCT05970172)

Development Overview

Introduction

Roxadustat is a first in class, orally administered, small molecule, being developed by FibroGen, in collaboration with Astellas and AstraZeneca, for the treatment of anaemia in patients with dialysis dependent chronic kidney disease (DD-CKD), non-dialysis dependent chronic kidney disease (NDD-CKD) and in patients with myelodysplastic syndromes (MDS), as well as for chemotherapy induced anaemia. The drug binds to and inhibits hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), an enzyme responsible for the degradation of transcription factors in the HIF family under normal oxygen conditions. This prevents HIF breakdown and promotes HIF activity. Increased HIF activity leads to an increase in endogenous erythropoietin production, thereby enhancing erythropoiesis. It also reduces the expression of the peptide hormone hepcidin, improves iron availability, and boosts haemoglobin (Hb) levels. HIF regulates the expression of genes in response to reduced oxygen levels, including genes required for erythropoiesis and iron metabolism. Roxadustat is launched in China, Japan, Germany, the United Kingdom, Netherlands and Austria. The drug is approved in the EU, Iceland, Norway, Liechtenstein, Chile, South Korea, Russia, Mexico and South Africa. Drug is under regulatory review in the US, Australia, Brazil, Canada, India, Philippines, Singapore, Taiwan, Thailand and Columbia for anaemia in patients with DD-CKD and NDD-CKD and for chemotherapy induced anaemia in China. Clinical development for anaemia and chemotherapy induced anaemia is underway in several countries worldwide.

As of September 2022, Astellas Pharma decided to discontinue the development in chemotherapy induced anaemia in his assigned territories [1] .

Preclinical development in sickle cell anaemia was discontinued in the US.

Company Agreements

In February 2024, FibroGen and AstraZeneca have agreed to terminate the U.S./RoW roxadustat collaboration agreement, which was signed on July 30, 2013, and under which AstraZeneca held development and commercialization rights in the United States and other non-China territories not licensed to Astellas Pharma Inc. According to a termination and transition agreement reached between the parties, AstraZeneca is returning all U.S./RoW roxadustat rights to FibroGen (with the exception of South Korea) and providing some assistance during the transition period. FibroGen's collaboration agreement with AstraZeneca for roxadustat in China remains in effect, and roxadustat is still the market leader in China by brand value share in the chronic kidney disease (CKD) anemia category. FibroGen will have certain financial obligations to AstraZeneca if it monetizes or commercializes roxadustat in the territories that were previously licensed under the U.S./RoW collaboration agreement. Earlier, in May 2021, FibroGen and AstraZeneca announced that they are also collaborating for the development and commercialization of roxadustat for the potential treatment of anemia in the U.S., China, other markets in the Americas, in Australia/New Zealand, and Southeast Asia. In July 2020, FibroGen and AstraZeneca entered into an amendment to revise the existing licence agreement for roxadustat in China. AstraZeneca is likely to recognise the overwhelming majority of its future revenue in China, from 2021 as product sales. In July 2013, AstraZeneca and FibroGen entered into a collaboration agreement for the development and commercialisation of roxadustat for the treatment of anaemia associated with chronic kidney disease and end-stage renal disease, and potentially other anaemia indications. The companies collaborated on the development in the US, China and all major markets except those that are covered by the agreement with Astellas. AstraZeneca had committed FibroGen an upfront and subsequent non-contingent payments amounting to $US350 million and potential future development related milestone payments of up to $US465 million, as well as milestone payments on future sales in addition to tiered royalty payments in the low 20% range. AstraZeneca is responsible for the US commercialisation of roxadustat and FibroGen will undertake specified promotional activities in the ESRD segment in this market. Post-marketing approval, FibroGen China will be responsible for management of manufacturing and medical affairs, while AstraZeneca will oversee promotional activities and commercial distribution. Additional development milestones will be payable for any subsequent indications which the companies choose to pursue. In July 2016, FibroGen received a scheduled license payment of $US62 million under its collaboration agreement with AstraZeneca. In June 2015, FibroGen received $US120 million non-contingent license payment from AstraZeneca under its collaboration agreements with the later. [2] [3] [4] [5] [6] [7] [8]

In May 2021, FibroGen entered into a collaboration with Astellas Pharma for the development and commercialization of roxadustat for the potential treatment of anemia in territories including Japan, Europe, Turkey, Russia and the Commonwealth of Independent States, the Middle East, and South Africa. In May 2022, FibroGen received $US25 million milestone payment upon registration of the candidate in Russia for anemia associated with chronic kidney disease (CKD). [3] [9]

In September 2004, FibroGen entered into an agreement with Yamanouchi to license FG 2216 and other related compounds, including roxadustat. Yamanouchi acquired exclusive rights to develop and market the compounds for the treatment of anaemia in Japan, while FibroGen retained the rights for the rest of the world. Yamanouchi merged with Fujisawa in April 2005, to form Astellas Pharma [10] . FibroGen has since licensed its oral HIF-PH inhibitors, including FG 2216 and roxadustat to Astellas Pharma for additional markets including, Europe, the Commonwealth of Independent States, the Middle East, and South Africa. FibroGen retains rights in the rest of the world, except Japan (where Astellas already has rights). Both the companies will share leadership of the clinical development programme in Europe and North America. Under the terms of the agreement, Astellas will pay a licensing fee, development milestones and will share costs of development and patent support [11] . Astellas made a payment of $US40 million to FibroGen based on the advancement of roxadustat into phase IIb testing for anaemia associated with chronic kidney disease in the fourth quarter of 2010 [12] .

Key Development Milestones

Before November 2021, Astellas has launched roxadustat in Germany, the United Kingdom, Netherlands and Austria [13] . In August 2021, Astellas received approval from the European Commission for roxadustat (EVRENZO™) for the treatment of adult patients with symptomatic anaemia associated with chronic kidney disease in the EU, Iceland, Norway and Liechtenstein. Earlier in June 2021, Astellas Pharma received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) for the use of roxadustat and the positive CHMP opinion was based on the data from a comprehensive pivotal phase III programme comprising of eight multicenter and randomised trials [see below]. Earlier in May 2020, the EMA had accepted the marketing authorization application (MAA) for review and the application is for the treatment of adult patients with CKD on dialysis and not on dialysis. The EC approval and acceptance of the MAA triggered a milestone payment of $US120 million and $US130 million, respectively, by Astellas to FibroGen [14] [15] [16] .

In November 2019, FibroGen announced that roxadustat is launched in China and Japan [17] .

Before August 2022, Roxadustat approved in Mexico for the treatment of CKD patients on dialysis and patients not on dialysis [18] .

Before August 2022, Roxadustat approved in South Africa for the treatment of CKD patients on dialysis and patients not on dialysis. Prior to this regulatory application was submitted to the regulatory agency [18] .

In May 2022, Astellas received approval for roxadustat in Russia for the treatment of adult patients with symptomatic anemia associated with chronic kidney disease (CKD) [9] .

Before July 2021, roxadustat is approved in South Korea for the treatment of anaemia of CKD in both non-dialysis dependent (NDD) and dialysis-dependent (DD) adult patients. As of July 2020, regulatory submission for roxadustat was made [19] [20] .

As of March 2021, roxadustat is approved in Chile for the treatment of anaemia of CKD in both non-dialysis dependent (NDD) and dialysis-dependent (DD) adult patients. Regulatory submissions for the same were made prior to July 2020 [21] [20] .

In August 2021, the US FDA issued a complete response letter regarding the NDA for roxadustat for the treatment of anaemia of chronic kidney disease (CKD). The letter indicated that the US FDA will not approve the roxadustat NDA in its present form and has requested additional clinical study of roxadustat be conducted, prior to resubmission [22] . In July 2021, the US FDA Cardiovascular and Renal Drugs Advisory Committee (CRDAC) voted to recommend not approving roxadustat for the treatment of anaemia due to chronic kidney disease (CKD) in adult patients. The Committee based its recommendation on data from a global phase III program. While the FDA is not required to follow the Committee's vote, the agency considers the Committee's non-binding recommendations when making its decision [19] . In April 2021, US FDA informed the FibroGen that it has tentatively scheduled a cardiovascular and Renal Drug Advisory Committee (CRDAC) on July 15, 2021 to review the New Drug Application (NDA) for roxadustat for the treatment of anaemia of chronic kidney disease (CKD) in both dialysis-dependent and non-dialysis-dependent patients. The NDA submission was supported by positive results from a global phase III program encompassing more than 8,000 patients [23] . Earlier in March 2021, FibroGen and AstraZeneca announced that the Cardiovascular and Renal Drugs Advisory Committee of the US FDA will hold an advisory committee (AdCom) meeting to review the new drug application for roxadustat in the US. In December 2020, the US FDA extended the review period of the NDA for roxadustat for the treatment of anaemia of chronic kidney disease (CKD) by three months. The updated Prescription Drug User Fee Act (PDUFA) action date was March 20, 2021. Earlier, in February 2020, the US FDA accepted the New Drug Application (NDA) of roxadustat for the treatment of anaemia of chronic kidney disease (CKD), in both non-dialysis-dependent (NDD) and dialysis-dependent (DD) CKD patients. The NDA was submitted by FibroGen in December 2019, to the US FDA, based on the results from the global phase III trials. The filing of the NDA triggered a $US50 million milestone payment from AstraZeneca [21] [24] [25] [26] .

In August 2019, the National Medical Products Administration (NMPA) granted marketing authorisation for roxadustat in China for the treatment of anaemia in non-dialysis-dependent chronic kidney disease (CKD) patients. The NMPA application was under review in May 2019. The NMPA had granted marketing authorisation to roxadustat for the treatment of anaemia in patients with dialysis-dependent CKD (DD-CKD) in China, in December 2018. The NDA was accepted for roxadustat for anaemia in dialysis-dependent CKD (DD-CKD) and non-dialysis-dependent CKD (NDD-CKD) patients by the China FDA in October 2017 and granted priority review. The NDA submission triggered $US15 million milestone payment to FibroGen by AstraZeneca. The NDA was based on the results of two phase III FGCL-4592-808 and FGCL-4592-806 [see below] studies [27] [28] [29] [30] [31] .

In September 2019, Japan's Ministry of Health, Labour and Welfare (MHLW) approved roxadustat tablet for the treatment of anaemia associated with chronic kidney disease (CKD) in dialysis patients. The approval is based on 1517-CL-0302, 1517-CL-0308, 1517-CL-0312 and 1517-CL-0307 trials [see below]. In October 2018, Astellas Pharma had submitted an NDA to Pharmaceuticals and Medical Devices Agency (PMDA) for marketing approval of roxadustat in Japan for the treatment of anaemia associated with chronic kidney disease (CKD) in patients on dialysis. The submission of NDA triggered a milestone payment of $US15 million milestone payment to FibroGen. The submission was based on the data from four phase III trials conducted in CKD patients on dialysis in Japan [see below] [32] [33] [34] .

Prior to November 2020, FibroGen and AstraZeneca submitted regulatory applications for roxadustat in the treatment of anaemia in patients with chronic kidney disease (CKD), in Thailand and Colombia [4] .

As of July 2020, FibroGen and AstraZeneca have made a number of regulatory submissions for roxadustat for the treatment of anaemia in patients with chronic kidney disease (CKD), in Australia, Brazil, India [35] [20] .

In December 2019, AstraZeneca submitted an applications for marketing approval of roxadustat for the treatment of anaemia in chronic kidney disease (CKD), in both non-dialysis-dependent (NDD) and dialysis-dependent (DD) CKD patients in Canada, Mexico, Taiwan, Philippines, and Singapore [36] . The NDS submitted in Canada was accepted for review in March 2020 (Health Canada website, September 2020).

In March 2022, Roxadustat included on the renewed 2021 National Reimbursement Drug List (“NRDL”), released by China’s National Healthcare Security Administration with a meaningful price reduction [37]

In November 2023, Astellas Pharma initiated a phase III trial to study the safety, pharmacodynamics, pharmacokinetics and activity of Roxadustat of anemia in pediatric patients with chronic kidney disease (NCT05970172; 1517-CL-1003). The open-label trial intends to enroll approximately 100 participants in Romania [38] .

In October 2020, FibroGen released pooled data from the roxadustat global phase III development program, examining associations between the achieved hemoglobin (Hb) levels and cardiovascular outcomes of both non-dialysis-dependent (NDD) and dialysis-dependent (DD) patients with anaemia of chronic kidney disease (CKD) which showed that roxadustat is effective in increasing and maintaining hemoglobin levels in patients with anaemia of chronic kidney disease and rates of cardiovascular events were lowest in patients when their hemoglobin levels were greater than 10 g/dL [39] .

In July 2021, FibroGen and AstraZeneca completed a phase IIIb trial that assessed the safety and effectiveness of roxadustat either as conversion from an Erythropoiesis Stimulating Agent (ESA), or as initial anaemia treatment in hemodialysis patients (FGCL4592-096; NCT04484857). The open-label trial was initiated in July 2020 and enrolled 283 patients in the US [40] .

In October 2021, FibroGen in collaboration with AstraZeneca initiated a phase IIIb trial to assess the safety and effectiveness of roxadustat in chronic dialysis anaemia patients converted from ESA therapy or who are ESA-naive (NCT04410198; FGCL-4592-097). The open-label trial initiated in May 2020 and enrolled 203 patients in the US [41] .

FibroGen announced in August 2015 that patient enrolment was ongoing in seven phase III clinical trials designed to support regulatory approval in the US and Europe [42] . Earlier, In June 2014, Astellas announced that six phase III studies in collaboration with FibroGen will support the European regulatory filings for both dialysis and non-dialysis-dependent CKD indications [43] . In August 2017, the data safety monitoring board recommended that the US and Europe phase III clinical studies proceed with no protocol modifications, following the completion of review of safety data [44] [45] [46] .
In March 2018, the Drug Safety and Monitoring Board (DSMB) recommended the continuation of the phase III trials of roxadustat in patients with anaemia in chronic kidney disease under current protocols [47] .

In December 2020, FibroGen released pooled phase III analysis data for anaemia in a total of 1530 patients with kidney failure incident to dialysis (clarifying and updating pooled ROCKIES, SIERRAS, HIMALAYAS [see below] in the journal of Kidney International Reports [3] .

In November 2019, AstraZeneca released detailed results from the phase III OLYMPUS and ROCKIES trials showing that roxadustat significantly increased hemoglobin (Hb) levels in both non-dialysis-dependent (NDD) and dialysis-dependent (DD) patients with anaemia from chronic kidney disease (CKD), respectively [48] [49] [50] .

In November 2019, the positive phase III pooled analysis data of safety and efficacy in a population with a broad range in both CKD and anaemia severity in over 8 000 patients across six phase III global trials (OLYMPUS, ANDES, ALPS, HIMALAYAS, SIERRAS, and ROCKIES) [see below] was released by FibroGen as well as AstraZeneca [51] [52] .

Anaemia in non-dialysis-dependent

chronic kidney disease patients: In November 2020, Astellas announced that roxadustat tablet (20mg, 50mg and 100mg) has received approval in Japan for the treatment of anaemia in non-dialysis-dependent (NDD) chronic kidney disease (CKD), in adult patients [53] [54] . This approval of the supplementary New Drug Application (sNDA) triggered a milestone payment of $15 million by Astellas to FibroGen. Earlier in January 2020, Astellas Pharma and FibroGen announced the submission of a supplemental New Drug Application (sNDA) to Japan's Ministry of Health, Labour and Welfare for the treatment of anaemia associated with chronic kidney disease (CKD) in non-dialysis dependent (NDD) patients. The sNDA for the use of roxadustat in NDD-CKD patients is supported by three studies in more than 500 Japanese patients [55] .

In December 2020, pooled efficacy data from three Phase III trials (ANDES, ALPS, and OLYMPUS) was presented at the 62nd Annual Meeting and Exposition of the American Society of Hematology (ASH-Hem-2020) [56] [50] [57] [58] .

In October 2018, AstraZeneca in collaboration with Fibrogen, completed a phase III trial that evaluated the safety and efficacy of roxadustat for treatment of anaemia in patients with stage 3, 4, or 5 chronic kidney disease that are not on dialysis (OLYMPUS; D5740C00001; NCT02174627; EudraCT2014-000770-19). The randomized, double-blind, placebo-controlled study was initiated in June 2014 and enrolled 2781 patients in Argentina, Brazil, Bulgaria, Canada, Colombia, Czech Republic, Germany, Hungary, India, Italy, Malaysia, Mexico, Peru, Philippines, Poland, Puerto Rico, Romania, Russia, Slovakia, South Korea, Spain, Taiwan, Thailand, Turkey, Ukraine, the US and Vietnam [59] [50] . In December 2018, AstraZeneca announced that the trial met its primary efficacy endpoint of statistically-significant and clinically-meaningful improvement in mean change from baseline in haemoglobin levels averaged over weeks 28 to 52 versus, placebo [60] . In March 2021, efficacy and safety data from the trial was published in the Journal of the American Society of Nephrology [3] .

In September 2018, Astellas Pharma reported that roxadustat met its primary endpoints in the pivotal phase III ALPS trial by exhibiting superiority in efficacy in comparison with placebo in terms of both haemoglobin (Hb) response rate in the first 24 weeks and Hb change from baseline at Weeks 28 to 52 (NCT01887600; EudraCT2012-005180-27; 1517CL0608; UKCRN16068; CCRN2087). The data from this trial will be used to support filing and reimbursement in Europe [61] . In November 2017, Astellas and FibroGen completed the study that assesseRegarding ESS password retrieval- Employee ID- 11937 (RDI- ADIS)d the efficacy and safety of roxadustat for the treatment of anaemia in patients with CKD not receiving haemodialysis. The double blind, multi-armed study was initiated in September 2013, and enrolled 597 patients in the UK, Belgium, Bulgaria, Italy, Poland, Romania, Russia, Spain, South Africa, Hungary, Greece, Belarus, Colombia, Dominican Republic, Estonia, Georgia, Guatemala, Panama, Peru, Serbia, Turkey and Ukraine. In February 2021, positive efficacy data from the trial including analysis of 594 patients was reported in the journal of Nephrology Dialysis Transplantation [3] [58] .

In August 2018, Astellas Pharma and FibroGen completed a phase III trial that evaluated the efficacy and the safety of intermittent oral dosing of roxadustat in erythropoiesis stimulating agent-untreated non-dialysis chronic kidney disease patients with anaemia (1517-CL-0314; NCT02964936). The non-randomised, parallel open-label study was initiated in January 2017 and enrolled 100 patients in Japan [62] .

In June 2017, FibroGen completed a phase III study that met its primary efficacy endpoint of correcting anaemia, by achieving a statistically significant increase in haemoglobin (Hb) levels, as compared with placebo over eight weeks (FGCL-4592-808; NCT02652819). FibroGen initiated the randomised, double-blind, placebo-controlled trial in December 2015, and enrolled 154 patients with CKD not on dialysis, in China. Roxadustat was safe and generally well-tolerated in the study, and the most frequent treatment emergent adverse events were typical for the patient population. Updated data were presented at the American Society of Nephrology Kidney Week 2018 annual meeting (ASN-2018). Further updated data were released in July 2019 [63] [64] [8] [65] [45] [42] [46] [66] .

In March 2020, Astellas Pharma and FibroGen, completed a phase III trial to evaluate the efficacy and the safety of intermittent oral dosing of roxadustat in erythropoiesis stimulating agent-treated non-dialysis dependant chronic kidney disease patients with anaemia (1517-CL-0310; NCT02988973). The active-controlled (darbepoetin alfa) conversion, open-label, parallel, randomised trial enrolled 334 patients in Japan [67] ..

In August 2016, pursuant to the review of phase III data for trials in China, the independent data safety monitoring board recommended continuation of the phase III trials without any amendments to the existing protocol [8] [68] .

In June 2020, the phase III Dolomites trial met the primary endpoint and demonstrated non-inferiority of roxadustat to darbepoetin in correction and maintenance of hemoglobin levels. In November 2019, Astellas completed the trial that evaluated the safety and efficacy of roxadustat, compared with commercially available darbepoetin alfa, for the treatment of anaemia in patients with chronic kidney disease who were not on dialysis [see RDI Profile 800008095] (1517-CL-0610; NCT02021318; EudraCT2013-000951-42). The randomised, open-label trial was initiated in December 2013 and enrolled 616 patients in the Ukraine, Austria, Belarus, Bulgaria, Croatia, Czech Republic, Denmark, France, Finland, Germany, Georgia, Hungary, Ireland, Israel, Latvia, Netherlands, Macedonia, Portugal, Montenegro, Poland, Romania, Russia, Slovakia, Serbia, Sweden, Slovenia, Spain and the UK. In June 2020, efficacy data from the trial were presented at the 57th European Renal Association – European Dialysis and Transplant Association (ERA-EDTA) [69] [70] .

Based on positive results from phase II trials, in December 2012 FibroGen and Astellas initiated a phase III clinical trial programme in Europe and the USA with roxadustat. Designed to support regulatory approval in Europe and the USA, the first trial of the phase III programme is assessing roxadustat in the treatment of anaemia associated with chronic kidney disease in patients receiving or not receiving dialysis [71] .

In September 2018, FibroGen and Astellas completed the phase III ANDES trial which evaluated the efficacy and safety of roxadustat in patients with chronic kidney disease not receiving dialysis (FGCL-4592-060; NCT01750190). The randomised, double-blind trial initiated in November 2012, enrolled 922 patients in the US, Mexico, Argentina, Chile, Colombia, Peru, Australia, New Zealand, South Korea, Puerto Rico, Hong Kong, Malaysia, Philippines, Singapore, Taiwan and Thailand [42] [57] . In December 2018, efficacy results from the trial were released by FibroGen [72] . In December 2020, efficacy data from the trial was peublished in the journal of Kidney International Reports [3] .

In July 2016, Astellas reported achievement of primary endpoint in a phase II trial that evaluated the safety and the dose-response of roxadustat in the treatment of anaemia in patients with non-dialysis CKD when roxadustat was applied intermittently (NCT01964196; 1517-CL-0303) [73] . The trial was completed in December 2015. The double-blind, randomised study initiated in August 2013, enrolled 107 patients in Japan [74] [75] .

In September 2012, FibroGen completed a phase IIb trial investigating the safety and efficacy of roxadustat in the treatment of anaemia in patients with stage 3 or 4 chronic kidney disease (CKD) not requiring dialysis (FGCL4592-041; NCT01244763). Four to six cohorts of patients were included and administered roxadustat for 16 or 24 weeks. The primary outcome was the haemoglobin (Hb) response to treatment (percentage of patients with Hb of 11 g/dL or more and an increase from baseline of at least 1 g/dL). The randomised, open-label, parallel trial was initiated in October 2010 and enrolled 145 patients in the US and Puerto Rico [12] [76] . Results from the study showed that roxadustat increased and maintained hemoglobin and decreased hepcidin levels in anaemic CKD patients when administered using multiple dosing strategies [77] [78] [79] .

FibroGen has completed its US-based phase IIa trial of roxadustat for the treatment anaemia associated with CKD (FGCL-SM4592-017; NCT00761657). This randomised, single-blind, placebo controlled, dose-ascending trial enrolled 134 patients with CKD not requiring dialysis. The study objectives were to assess the safety, pharmacokinetics and pharmacodynamics of roxadustat (1.0-3.0 mg/kg) and to obtain exploratory efficacy data [80] . Data from this trial were presented in November 2010 [81] . This trial was previously put on clinical hold at the request of the US FDA in May 2007 due to one case of death by fulminant hepatitis during this trial; however, in March 2008, the hold was lifted and development resumed [82] . Patient enrolment was resumed in January 2009 [83] . The results of the trial were released by the company on August 2015 [84] .

In December 2019, FibroGen completed a phase II/III trial that investigated the long term (two years) safety and efficacy of roxadustat (FGCL-4592-059; NCT01630889). The open-label trial was initiated in May 2012, and enrolled 15 patients with chronic kidney disease, who were receiving dialysis or not receiving dialysis, in the US and Puerto Rico [85] .

FibroGen completed a randomised, double-blind, placebo-controlled phase II trial in January 2013, to assess the efficacy and safety of roxadustat for the treatment of anaemia in 91 non-dialysis dependent Chinese patients with CKD (FGCL-4592-047; NCT01599507). Roxadustat was given for 8 weeks, in low-dose and high-dose cohorts. Results were reported in November 2013 [86] [87] [88] . Data from the trial were published in the journal Nephrology Dialysis Transplantation in March 2017 [89] .

Anaemia in dialysis-dependent

chronic kidney disease patients: In June 2019, FibroGen initiated a phase IV trial to investigated the efficacy and relative safety of multiple dosing regimens of roxadustat over a 36-week treatment for the treatment of anaemia in patients with end-stage renal disease who are on dialysis (FGCL-4592-818; NCT04059913). The randomised, open-label trial intends to recruit 306 patients in China [90] .

Pooled results from the three phase III trials, OLYMPUS, ANDES and ALPS, trials [see below] showed that roxadustat consistently improved anaemia in patients with non-dialysis-dependent chronic kidney disease patients (NDD-CKD). The overall safety of roxadustat was comparable with placebo and consistent with the CKD patient population. In December 2020, efficacy esults from the trials were presented at the 62nd Annual Meeting and Exposition of the American Society of Hematology (ASH-2020) [91] [50] [58] [57] [92] [93] . In December 2021, data pooled from three pivotal, randomized, phase III studies of roxadustat vs placebo NDD CKD populations and a phase III study of roxadustat vs darbepoetin alfa in NDD CKD was presented at the 63rd Annual Meeting and Exposition of the American Society of Hematology (ASH-HEM-2021) [94] .

In July 2022, FibroGen and AstraZeneca withdrew its phase III trial before enrolment due to sponsor's decision. Earlier in November 2020, trial was initiated to evaluate the efficacy, safety and pharmacokinetics of roxadustat for the treatment of anaemia in pediatric patients with chronic kidney disease who are receiving either hemodialysis (HD) or peritoneal dialysis (PD) (FGN-PED-CLIN-02; NCT04621331). The open label trial was initiated in the US [95] .

In September 2018, AstraZeneca completed a phase III trial that investigated the safety and efficacy of roxadustat compared with epoetin alfa for the treatment of anaemia in chronic kidney disease patients on dialysis (ROCKIES; NCT02174731; D5740C00002; EudraCT2014-000780-40). The randomised, open-label trial was initiated in July 2014 and enrolled 2133 patients in the Argentina, Australia, Brazil, Bulgaria, Canada, Czech Republic, Hungary, India, Mexico, Peru, Philippines, Poland, Romania, Russia, Slovakia, Spain, Sweden, Thailand, Ukraine, the US and Vietnam. FibroGen announced the completion of patient enrolment in US, in June 2018 [59] [49] . In December 2018, AstraZeneca announced that the trial met its primary efficacy endpoint of statistically-significant improvement in mean change from baseline in haemoglobin levels averaged over weeks 28 to 52 versus, epoetin alfa [60] .

In July 2018, Astellas and FibroGen completed the phase III Pyrenees trial that evaluated the efficacy and safety of roxadustat compared with epoetin alfa for the treatment of anaemia in patients with end-stage renal disease who are on dialysis (1517-CL-0613 ; NCT02278341; EudraCT2013-001497-16). Evaluation of the change in haemoglobin was the primary endpoint of the trial. The randomised, open-label trial was initiated in November 2014, and enrolled 838 patients in the UK, Belgium, Bulgaria, Croatia, Czech Republic, France, Georgia, Germany, Hungary, Italy, Poland, Portugal, Romania, Russia, Spain, Slovakia and Serbia. As of October 2019, the trial met its primary endpoint [96] [97] .

In March 2018, Astellas Pharma and FibroGen, completed a phase III trial that assessed the safety and efficacy of roxadustat compared with darbepoetin alfa in haemodialysis dependent chronic kidney disease patients with anaemia (1517-CL-0307; NCT02952092). The randomised, double-blind, parallel trial was initiated in November 2016 and enrol 303 patients in Japan. In May 2018, company released the topline data from the trial. In October 2018, updated data were presented at the American Society of Nephrology Kidney Week 2018 annual meeting (ASN-2018). In June 2020, data from the trial were presented at the European Renal Association – European Dialysis and Transplant Association (ERA-EDTA) [98] [99] [100] [101] .

In December 2017, Astellas in collaboration with FibroGen, completed an open-label, randomised phase III trial that evaluated the safety and efficacy of intermittent oral dosing of roxadustat in chronic kidney disease patients with anaemia, who are undergoing haemodialysis and have not received prior therapy with erythropoiesis stimulating agent (ESA-naive) (1517-CL-0308; NCT02780141). The trial was initiated in June 2016 and enrolled 75 patients in Japan. In July 2016, the first patient was dosed in the phase III trial, triggering a milestone payment of $US10 million to FibroGen from Astellas [73] [102] .

In November 2017, Astellas Pharma completed a long-term phase III trial that evaluated the efficacy and safety of roxadustat in haemodialysis patients with renal anaemia whose treatment is converted from an erythropoieses stimulating agent formulation (1517-CL-0312; NCT02779764). The single-group, open-label trial was initiated in May 2016 and enrolled 164 patients in Japan [103] .

In August 2017, Astellas, in collaboration with FibroGen, completed an open-label, randomised phase III trial that evaluated the safety and efficacy of intermittent oral dosing of roxadustat in chronic kidney disease patients with anaemia, who were undergoing peritoneal dialysis (1517-CL-0302; NCT02780726). The trial was initiated in June 2016 and enrolled 56 patients in Japan. The initiation of the trial has triggered a $US10 million milestone payment from Astellas to FibroGen, which the latter company was to receive by July 2016 [104] [105] . In October 2017, the company released positive data from the phase III trial. In October 2018, updated data were presented at the American Society of Nephrology Kidney Week 2018 annual meeting (ASN-2018) [99] [106]

In June 2017, FibroGen completed a phase III trial that met its primary endpoint of mean change in haemoglobin from baseline (FGCL-4592-806; NCT02652806). The trial evaluated the safety and efficacy of roxadustat, for the treatment of anaemia in patients with CKD on dialysis. The randomised, open-label, active-controlled (epoetin alfa) trial was initiated in December 2015, and enrolled 304 patients in China. Roxadustat was safe and generally well-tolerated in the study, and the most frequent treatment emergent adverse events were typical for the patient population. Updated data were presented at the American Society of Nephrology Kidney Week 2018 annual meeting (ASN-2018) [64] [8] [45] [107] .

In September 2018, FibroGen completed the phase III SIERRAS trial, which evaluated the safety and efficacy of roxadustat compared with epoetin alfa as a maintenance treatment for anaemia in patients with end stage renal disease who are on stable dialysis (FGCL4592-064; NCT02273726). The primary endpoint was the change in haemoglobin level from baseline, assessed during weeks 28 to 52. The randomised open-label trial initiated in December 2014, enrolled 741 patients in the US and Puerto Rico. FibroGen announced the completion of patient enrolment in US, in June 2018 [59] [42] [108] . In December 2018, efficacy results from the trial were released by FibroGen [72] . In April 2021, the efficacy data from the trial was published in Kidney International Reports [3] .

In September 2018, FibroGen completed the phase III HIMALAYAS trial, which evaluated the safety and efficacy of roxadustat tablets in patients with anaemia due to end-stage renal disease who are on dialysis (FGCL-4592-063; NCT02052310; EudraCT2013-002753-30). The randomised, open-label trial initiated in December 2013, enrolled 1043 patients in the US, Argentina, Bulgaria, Chile, Colombia, South Korea, Russia, Estonia, Latvia, Malaysia, Mexico, Poland, Romania, Taiwan, Thailand and Ukraine. FibroGen announced the completion of patient enrolment in US, in June 2018 [59] [42] [109] . In November 2019, updated efficacy and safety results from the trial were released by FibroGen. In February 2021, the company published efficacy data from the trial in the journal of Nephrology Dialysis Transplantation [3] [110] [72] .

In July 2016, Astellas reported achievement of primary endpoint in a phase II trial of the safety and efficacy of intermittent oral dosing with roxadustat for the treatment of anaemia in haemodialysed patients with CKD, in comparison to the reference drug, darbepoetin (1517CL0304; NCT01888445) [73] . The trial was completed in September 2014, Astellas completed The randomised, open-label, double-blind trial was initiated in May 2013 and enrolment of 130 patients was completed in Japan, in April 2014. The initiation of this trial triggered a $US12.5 million milestone payment from Astellas to FibroGen [75] [111] . FibroGen released clinical data indicating increased soluble transferrin receptor in patients with chronic kidney disease and treated with roxadustat [112] .

In May 2013, FibroGen completed an open-label phase II trial to assess the efficacy and safety of roxadustat in the treatment of anaemia in patients with end-stage renal disease who recently started dialysis (FGCL-4592-053; NCT01414075). The study was initiated in July 2011 and enrolled 55 patients in the US, Hong Kong, Russia and Singapore. Preliminary data were reported in November 2012. These data also showed that roxadustat allowed integration of red blood cell production and iron incorporation simultaneously. In October 2015, the company released additional clinical data from the trial [113] [114] [115] .

The phase IIb, randomised, double-blind, placebo- and active-controlled trial evaluating roxadustat in patients with end-stage kidney disease (ESKD) on maintenance dialysis was completed in July 2013 (FGCL4592-040; NCT01147666). Patients were categorised based on responsiveness to erythropoiesis-stimulant therapy (normoresponsive or hyporesponsive). This trial was initiated in March 2010 and enrolled 144 patients in the US [12] [116] . Interim data showed that roxadustat corrected and maintained haemoglobin levels for 19 weeks without IV iron supplementation in patients previously receiving maintenance epoetin alfa [117] . In February 2016, FibroGen released data from the study [118] .

In January 2013, FibroGen completed a phase II trial which the efficacy and safety of roxadustat in patients with end stage renal disease receiving haemodialysis. The open label, randomised trial enrolled 96 patients in China (FGCL-4592-048; NCT01596855) [119] [88] . Data from the trial were published in the journal Nephrology Dialysis Transplantation in March 2017 [89] .

The phase IIb programme of roxadustat in anaemia of chronic disease (ACD) patients on haemodialysis was initiated following the establishment of clinical proof-of-principle following the enrolment of 50 haemodialysis patients in a phase IIa, dose-escalation trial in October 2010. The phase IIa trial enrolled patients with stage 5 CKD (end-stage renal disease) with anaemia. Patients were stratified based on responsiveness to erythropoiesis-stimulants (normoresponsive or hyporesponsive). Oral roxadustat was dosed between 1.0 mg/kg and 2.0 mg/kg, thrice-weekly. Results have been reported [12] .

In September 2010, FibroGen received Clinical Trial Application (CTA) approval from the Chinese State Food and Drug Administration (SFDA) to commence clinical development of roxadustat for the treatment of anaemia associated with CKD in China [81] [120] . Phase I trials have been completed and phase II studies are underway [78] . Two phase 3 studies required for regulatory approval in China are expected to begin enrolment in the fourth quarter of 2015 [42] [46] [107] .

Anaemia in myelodysplastic syndrome

(MDS): In August 2023, AstraZeneca in collaboration with FibroGen terminated a phase III MATTERHORN trial which evaluated the efficacy and safety of roxadustat for the treatment of anaemia in transfusion-dependent lower risk myelodysplastic syndrome patients, as the did not meet its primary efficacy endpoint (FGCL4592-082; NCT03263091; EudraCT2017-001773-17). The trial was completed in June 2023. In May 2019, FibroGen reported completion of enrolment in the open-label phase of the trial and initiated patient dosing in the double-blind, placebo-controlled portion of the trial. The parallel, prospective, randomised trial initiated in September 2017, enroled 140 patients in the US, Australia, Germany, Belgium, Israel, Italy, South Korea, Russia, UK, Denmark, Canada, France, India, Poland, Turkey and Spain [28] [121] [68] [122] . In December 2019, FibroGen released safety and efficacy results from the trial at the 61st Annual Meeting and Exposition of the American Society of Hematology (ASH-2019) [123] . As of August 2022, FibroGen completed enrollment of 140 patients in the phase III MATTERHORN trial [124] . In May 2023, company released the data from the trial [125] . In December 2023, the company presented the data from the trial at the 65th American Society of Hematology Annual Meeting and Exposition (ASH-Hem-2023) [126] .

In February 2023, FibroGen, in collaboration with AstraZeneca, completed a phase II/III trial, which assessed the efficacy and safety of roxadustat, for the treatment of anaemia, in Chinese participants with lower risk MDS (FGCL-4592-813; NCT03303066). The randomised trial was initiated in June 2018, and enrolled 43 patients in China [127] [128] .

In March 2017, FibroGen announced that the China Food and Drug Administration (CFDA) had approved the CTA for a phase II/III trial in patients with anaemia with MDS [129] [8] .

Chemotherapy-induced anaemia

As of September 2023, National Medical Products Administration (NMPA) China accepted the supplemental New Drug Application (sNDA) for roxadustat for the treatment of patients with chemotherapy-induced anemia (CIA). The company expects the decision in mid-2024 [130] . As of August 2023, FibroGen submitted sNDA to the National Medical Products Administration (NMPA) China for chemotherapy-induced anaemia [131] [132] .

As of September 2022, Astellas Pharma decided to discontinue the development in chemotherapy induced anaemia in assigned territories [1] .

In April 2023, FibroGen completed a phase III trial that evaluated the efficacy and safety of roxadustat for the treatment of chemotherapy induced anaemia (NCT05301517; FGCL-4592-898). The randomised, open-label, active-controlled, multicenter trial, initiated in March 2022, enrolled 159 patients in China [133] . In the preliminary safety analysis, the adverse event profile of roxadustat was generally consistent with previous findings and supportive of a positive benefit risk in this patient population [131] . In October 2023, efficacy data from the trial presented at the 48th European Society for Medical Oncology Congress (ESMO-2023) [134] .

In August 2021, FibroGen announced that the phase II WHITNEY trial met primary endpoint of maximum change in haemoglobin within 16 weeks from baseline without red blood cell transfusion in patients with non-myeloid malignancies with chemotherapy induced anaemia. In the trial, roxadustat was generally well tolerated and there were no substantive differences in treatment-emergent adverse events (TEAEs) between arms with different starting doses. In April 2021, FibroGen in collaboration with AstraZeneca and Astellas Pharma completed the trial which evaluated the safety and efficacy of roxadustat in chemotherapy induced anaemia patients (FGCL-4592-092; NCT04076943). This open-label study was initiated in August 2019 and enrolled 92 patients in the US [135] [136] . Later, in June 2022, the company presented efficacy and safety data at the 58th Annual Meeting of the American Society of Clinical Oncology (ASCO-2022) [137]

Sickle cell anaemia

Studies of roxadustat in preclinical models of sickle cell disease were funded by a Small Business Innovation Research (SBIR) grant from the National Heart, Lung and Blood Institute of the National Institutes of Health (NIH). FibroGen received the phase II SBIR grant from the NIH in August 2006 for preclinical evaluation of hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitors in sickle cell disease. Earlier preclinical studies indicated that certain HIF-PH inhibitors had therapeutic potential in sickle cell disease by combining erythropoietic activity with the ability to disproportionately raise fetal haemoglobin [138] . No recent development for this indication has been reported on the FibroGen website as of March 2011. It is therefore assumed that development for this indication has been discontinued.

Early stage development

In October 2019, Astellas Pharma in collaboration with FibroGen completed a phase I trial that evaluated the relative bioavailability of roxadustat following a single dose of pediatric azo dye-free tablet and pediatric azo dye-free mini-tablet (Solid and Suspension) compared to a Single Dose of Azo Dye-containing Tablet in Healthy Adult volunteers(NCT03960489; EudraCT2018-002924-18; 1517-CL-1001). The randomised, cross-over study, initiated in July 2019, enrolled 24 healthy volunteers in Germany [139] .

In December 2017, Astellas Pharma and FibroGen completed a phase I trial that evaluated the pharmacokinetics of roxadustat and its main metabolites in subjects with normal renal function or severely impaired renal function (1517-CL-0543; EudraCT2015-002565-28; NCT02965040). The non-randomised, parallel open-label study was initiated in December 2016, and enrolled 34 patients in the UK and Germany [140] .

In December 2016, Astellas Pharma and FibroGen completed a phase I trial that assessed the effect of lanthanum carbonate hydrate [see Adis Insight Drug profile 800008627] on the pharmacokinetics of roxadustat in non-elderly healthy male volunteers (1517-CL-0205; NCT02952040). The open-label, crossover, randomised trial was initiated in November 2016, and recruited 18 volunteers in Japan [141] .

In August 2016, Astellas Pharma and FibroGen completed a phase I trial, which assessed the effect of food on the pharmacokinetics of a single oral dose of roxadustat in non-elderly healthy adult male volunteers (1517-CL-0202; NCT02805374). The open-label, crossover, randomised trial was initiated in July 2016 and enrolled 16 volunteers in Japan [142] .

In April 2016, Astellas Pharma in collaboration with FibroGen completed a phase I trial, which investigated the effect of Kremezin® [see RDI profile 800009198] on the pharmacokinetics of single dose of roxadustat in healthy male volunteers (NCT02693613; 1517-CL-0204). The open-label, randomised trial enrolled 34 healthy volunteers in Japan [143] .

Astellas Pharma Europe and FibroGen initiated a randomised, double-blind, placebo-controlled, crossover phase I trial in September 2013 to assess the pharmacokinetics and dose-proportionality of roxadustat in healthy young and elderly volunteers (NCT02161796; EudraCT2013-001044-57). The trial enrolled 48 subjects in Germany and was completed in December 2013 [144] .

Astellas and FibroGen completed a phase I trial in December 2013 to assess the exposure, safety and tolerability of single doses of roxadustat in subjects with moderate hepatic impairment, compared to healthy volunteers (NCT02161224; EudraCT2013-001533-41). The trial enrolled 16 subjects in Bulgaria [145] .

In November 2013, Astellas completed a phase I trial that investigated the effect of multiple doses of roxadustat on a single dose of warfarin in healthy volunteers (1517CL0509; NCT02252731; EudraCT2013-001043-31). The open-label trial enrolled 22 subjects in the Germany. The trial began in September 2013 [146] .

A phase I trial evaluating the pharmacokinetics and pharmacodynamics of single doses of roxadustat in 12 patients with renal anaemia on dialysis (1517-CL-0203; NCT01083888) and a phase I trial in 100 healthy non-elderly adult volunteers (1517-CL-0201; NCT00978198) were completed in Japan, in June 2010 [78] [71] [147] [148] .

In June 2010, FibroGen completed an open-label phase I trial to assess the potential pharmacokinetic interaction between roxadustat and rosiglitazone in healthy volunteers (FGCL-4592-037; NCT01376063). The trial enrolled 20 subjects in the US [149] .

A phase I trial evaluating roxadustat in healthy volunteers was completed by FibroGen in the US. Early results from the dose-escalation study demonstrated the potential for roxadustat to treat anaemia, as evidenced by increases in endogenous erythropoietin significantly above baseline following a single oral dose. No adverse events related to treatment were reported [150] .

In May 2015, FibroGen completed two-year non-clinical carcinogenicity studies in rats and mice, in which there was no evidence of roxadustat-related effect on carcinogenicity or mortality. The event triggered a $US15 million milestone payment from AstraZeneca to FibroGen [151] .

Patent Information

As t Decmber 2020, FibroGen has patents pending in Canada and Japan. In addition, FibroGen initiated various legal actions for its portfolio facing various legal actions in several territories, including in Europe, the United Kingdom, Canada, and Japan. A settlement has been reached in the litigation in Canada, resulting in the discontinuance of the action and leaving FibroGen’s Canadian patents valid and enforceable [152]

As at February 2018, FibroGen holds multiple US patents and some patents in China for for roxadustat, its composition of matter, pharmaceutical compositions containing roxadustat and for methods for treating anemia using roxadustat or its analogues. These patents are valid through 2024 or 2025. The patents for crystalline form of roxadustat in the US and China, are set to expire in 2033 [153] .

In April 2020, FibroGen announced that the United Kingdom's High Court of Justice has held certain patents to be invalid, that were related to methods of using hypoxia-inducible factor prlyl hydroxylase inhibitors. The decision of the court will not affect the validity of patents in the rest of Europe [154] .

In June 2017, the European Patent Office maintained a FibroGen's European patent number 2 322 153, entitled "Use of HIF alpha stabilisers for enhancing erythropoiesis", related to the therapeutic use of certain small molecule inhibitors of hypoxia-inducible factor (HIF) prolyl hydroxylase. The patent validated the claims related to increasing serum iron in the treatment of iron deficiency and the use of structural mimetics of 2-oxoglutarate that inhibit HIF prolyl hydroxylase (HIF-PH) activity. The patent opposition was filed by Akebia Therapeutics, three companies in the Bayer Group (Bayer Intellectual Property, Bayer Pharma Aktiengesellschaft, Bayer Animal Health) and Glaxo Group Limited were deemed invalid [155] .

In June 2017, the European Patent Office ruled against FibroGen's European patent number 2 322 155, entitled "Use of HIF alpha stabilisers for enhancing erythropoiesis". The patent is being disputed by Akebia Therapeutics, three companies in the Bayer Group, and Glaxo Group. FibroGen has appealed the decision against the ‘155 patent [155] .

In June 2013, European Patent Office (EPO) granted the ’823 patent (European Patent 1 463 823 ) to FibroGen, which claimed, among other things, the use of a heterocyclic carboxamide compound selected from the group consisting of pyridine carboxamides, quinoline carboxamides, isoquinoline carboxamides, cinnoline carboxamides, and beta-carboline carboxamides that inhibits HIF-PH enzyme activity in the manufacture of a medicament for increasing endogenous erythropoietin in the prevention, pretreatment or treatment of anaemia. In December 2013, Akebia filed an opposition to the ’823 patent requesting that the ’823 patent be revoked in its entirety. The Opposition Division issued a non-binding preliminary opinion that none of the ’823 patent’s claims met the requirements for patentability in August 2015. Akebia announced that the OD of the EPO has revoked FibroGen's ’823 patent in its entirety in March 2016 [156] .

Our roxadustat patent portfolio includes multiple granted U.S. patents offering protection for roxadustat, including protection for roxadustat composition-of-matter, for pharmaceutical compositions containing roxadustat, and for methods for treating anemia using roxadustat or its analogs. Exclusive of any patent term extension, the granted U.S. patents relating to the composition-of-matter of roxadustat are due to expire in 2024 or 2025, and granted foreign patents are due to expire in 2024. U.S. and foreign patents relating to crystalline forms of roxadustat are due to expire in 2033, and U.S. and foreign patents relating to photostable formulations of roxadustat are due to expire in 2034.

In 2020, oppositions were filed against our European Patent No. 2872488 (the “`488 Patent”), which claims a crystalline form of roxadustat, and our European Patent No. 3003284 (the “`284 Patent”), which claims photostable formulations of roxadustat. Final resolution of the opposition proceedings will take time and we cannot be assured that all or any claims will remain.
We believe that, if roxadustat is approved, a full five-year patent term extension under the Hatch-Waxman act will be available for a granted U.S. patent relating to roxadustat, which extension would expire in 2029 or 2030, depending on the patent extended. Refer to “Government Regulation — Regulatory Exclusivity for Approved Products — U.S. Patent Term Restoration.”
We also hold various U.S. and foreign granted patents and pending patent applications directed to manufacturing processes, formulations, and methods for use of roxadustat
Roxadustat China Patent Portfolio

Drug Properties & Chemical Synopsis

  • Route of administration PO
  • Formulation Tablet, unspecified
  • Class Amides, Antianaemics, Carboxylic acids, Isoquinolines, Small molecules
  • Target Hypoxia-inducible factor-proline dioxygenase
  • Mechanism of Action Hypoxia-inducible factor-proline dioxygenase inhibitors
  • WHO ATC code

    B03X-A05 (Roxadustat)

  • EPhMRA code

    B3 (Anti-Anaemic Preparations)

  • Chemical name (((4-Hydroxy-1-methyl-7-phenoxyisoquinolin-3- yl)carbonyl)amino)acetic acid
  • Molecular formula C19 H16 N2 O5
  • SMILES C(CNC(=O)C1N=C(C2=C(C=1O)C=CC(=C2)OC1C=CC=CC=1)C)(=O)O
  • Chemical Structure
  • CAS Registry Number 808118-40-3

Biomarkers Sourced From Trials

Indication Biomarker Function Biomarker Name Number of Trials

anaemia

Arm Group Label

Gluconic acid

Fumaric acid

flotillin 2

Erythropoietin (EPO)

egl-9 family hypoxia inducible factor 2

Angiotensin-converting enzyme (ACE

1

1

1

2

1

1

anaemia

Outcome Measure

Vascular endothelial growth factor A (VEGF)

TF

Soluble transferrin receptor

protease, serine 33

Interleukin-6 (IL-6)

Interleukin-2 (IL-2)

Interleukin-17 (IL-17)

IKAROS family zinc finger 4

hydroxysteroid (17-beta) dehydrogenase 4

Hepcidin

group-specific component (vitamin D binding protein)

flotillin 2

Ferritin

Erythropoietin (EPO)

EOS

D-box binding PAR bZIP transcription factor

Creatinine

C-reactive protein (CRP)

1

13

7

1

1

1

1

1

2

4

2

1

13

3

1

2

1

6

anaemia

Brief Title

egl-9 family hypoxia inducible factor 2

1

anaemia

Arm Group Description

ubiquitin specific peptidase 1

Gluconic acid

Fumaric acid

flotillin 2

Erythropoietin (EPO)

egl-9 family hypoxia inducible factor 2

2

1

1

1

2

1

anaemia

Eligibility Criteria

TNF alpha induced protein 1

TF

PTH

NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 3, 12kDa

L-Aspartic acid

HFE

Folic acid

flotillin 2

Ferritin

Erythropoietin (EPO)

Cyanocobalamin

Cobalamin

C-reactive protein (CRP)

Bilirubin

ALT

1

14

2

1

1

1

15

1

17

2

14

14

1

1

1

anaemia

Official Title

EPOR

egl-9 family hypoxia inducible factor 2

1

1

cardiovascular disorders

Arm Group Label

Erythropoietin (EPO)

Angiotensin-converting enzyme (ACE

1

1

hypoxia

Outcome Measure

TIMP-2

NGAL

IGFBP7

Cystatin C

Creatinine

Cardiac Troponin I

BNP

1

1

1

1

1

1

1

ischaemia

Outcome Measure

TIMP-2

NGAL

IGFBP7

Cystatin C

Creatinine

Cardiac Troponin I

BNP

1

1

1

1

1

1

1

kidney disorders

Arm Group Label

Erythropoietin (EPO)

Angiotensin-converting enzyme (ACE

1

1

myocardial infarction

Outcome Measure

CKM

CKB

Cardiac Troponin I

1

1

1

renal failure

Detailed Description

Creatinine

1

renal failure

Eligibility Criteria

Uric acid

1

renal failure

Outcome Measure

Erythropoietin (EPO)

1

Biomarker

Drug Name Biomarker Name Biomarker Function
Roxadustat - FibroGen ALT Eligibility Criteria
Angiotensin-converting enzyme (ACE Arm Group Label
Bilirubin Eligibility Criteria
BNP Outcome Measure
C-reactive protein (CRP) Eligibility Criteria, Outcome Measure
Cardiac Troponin I Outcome Measure
CKB Outcome Measure
CKM Outcome Measure
Cobalamin Eligibility Criteria
Creatinine Detailed Description, Outcome Measure
Cyanocobalamin Eligibility Criteria
Cystatin C Outcome Measure
D-box binding PAR bZIP transcription factor Outcome Measure
EOS Outcome Measure
EPOR Official Title
Erythropoietin (EPO) Arm Group Description, Arm Group Label, Eligibility Criteria, Outcome Measure
Ferritin Eligibility Criteria, Outcome Measure
flotillin 2 Arm Group Description, Arm Group Label, Eligibility Criteria, Outcome Measure
Folic acid Eligibility Criteria
Fumaric acid Arm Group Description, Arm Group Label
Gluconic acid Arm Group Description, Arm Group Label
group-specific component (vitamin D binding protein) Outcome Measure
Hepcidin Outcome Measure
HFE Eligibility Criteria
hydroxysteroid (17-beta) dehydrogenase 4 Outcome Measure
IGFBP7 Outcome Measure
IKAROS family zinc finger 4 Outcome Measure
L-Aspartic acid Eligibility Criteria
NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 3, 12kDa Eligibility Criteria
NGAL Outcome Measure
protease, serine 33 Outcome Measure
PTH Eligibility Criteria
Soluble transferrin receptor Outcome Measure
TF Eligibility Criteria, Outcome Measure
TIMP-2 Outcome Measure
TNF alpha induced protein 1 Eligibility Criteria
ubiquitin specific peptidase 1 Arm Group Description
Uric acid Eligibility Criteria
Vascular endothelial growth factor A (VEGF) Outcome Measure
For more detail, check out BiomarkerBase: the leading source of information about biomarkers used in drug development and diagnostic tests, tracking a comprehensive list of biomarker uses worldwide by over 800 companies

Development Status

Summary Table

Indication Qualifier Patient Segment Phase Countries Route / Formulation Developers Event Date
Anaemia in non-dialysis-dependent (NDD) and dialysis-dependent (DD) CKD patients - Marketed Austria, Germany, Netherlands, United Kingdom PO / Tablet Astellas Pharma 09 Nov 2021
Anaemia in non-dialysis-dependent (NDD) and dialysis-dependent (DD) CKD patients - Marketed Japan PO / Tablet Astellas Pharma, FibroGen 01 Nov 2019
Anaemia in non-dialysis-dependent (NDD) and dialysis-dependent (DD) CKD patients - Marketed China PO / Tablet AstraZeneca, FibroGen 11 Nov 2019
Anaemia in non-dialysis-dependent (NDD) and dialysis-dependent (DD) CKD patients - Registered European Union, Iceland, Liechtenstein, Norway, Russia, South Africa PO / Tablet Astellas Pharma, FibroGen 08 Aug 2022
Anaemia in non-dialysis-dependent (NDD) and dialysis-dependent (DD) CKD patients - Registered Chile, Mexico, South Korea PO / Tablet AstraZeneca, FibroGen 08 Aug 2022
Anaemia in non-dialysis-dependent (NDD) and dialysis-dependent (DD) CKD patients - Preregistration Australia, Brazil, Canada, Colombia, India, Philippines, Singapore, Taiwan, Thailand, USA PO / Tablet AstraZeneca, FibroGen 01 Nov 2020
Anaemia in non-dialysis-dependent (NDD) and dialysis-dependent (DD) CKD patients - Phase III Belarus, Dominican Republic, Georgia, Greece, Guatemala, Israel, Macedonia, Montenegro, Panama, Serbia PO / Tablet Astellas Pharma, FibroGen 01 Nov 2014
Anaemia - - Phase III Belgium, Denmark, France, Italy, Poland, Spain PO / Tablet AstraZeneca 07 Sep 2017
Anaemia - In adolescents, In children, In infants Phase III Romania PO / Tablet Astellas Pharma 26 Dec 2023
Anaemia in non-dialysis-dependent (NDD) and dialysis-dependent (DD) CKD patients - Phase III Puerto Rico, Turkey, Ukraine, Vietnam PO / Tablet AstraZeneca, FibroGen 18 Sep 2015
Anaemia In CKD patients receiving either hemodialysis (HD) or peritoneal dialysis (PD) aging 2 to <18 years In adolescents, In children Phase III USA PO / Tablet AstraZeneca, FibroGen 01 Nov 2020
Anaemia in non-dialysis-dependent (NDD) and dialysis-dependent (DD) CKD patients - Phase III Argentina, Hong Kong, Malaysia, New Zealand, Peru PO / Tablet Astellas Pharma, FibroGen, AstraZeneca 24 Sep 2015
Chemotherapy-induced anaemia - - Preregistration China PO / unspecified FibroGen 07 Aug 2023
Chemotherapy-induced anaemia - - Phase II USA PO / unspecified AstraZeneca, FibroGen 06 Aug 2019
Sickle cell anaemia - - Discontinued (Preclinical) USA PO / Tablet FibroGen 29 Mar 2011

Commercial Information

Involved Organisations

Organisation Involvement Countries
FibroGen Originator USA
FibroGen Owner USA
Astellas Pharma Licensee Commonwealth of Independent States, Europe, Japan, Middle East, Russia, South Africa, Turkey
AstraZeneca Licensee China, South Korea
National Institutes of Health Funder
FibroGen China Collaborator China

Brand Names

Brand Name Organisations Indications Countries
EVRENZO Astellas Pharma Anaemia Liechtenstein, China, Iceland, Norway, European Union
Evrenzo Astellas Pharma Anaemia Japan

Credit Suisse Market Status

Indication Region Company Phase Expected Launch Year Probability of Success% Patent Expiry Year Expected Generic Entry Last Update
Renal Anaemia China Astellas Pharma, AstraZeneca, FibroGen Marketed 2020 100 2033 01 Jun 2033 05 Nov 2023
Renal Anaemia Japan Astellas Pharma, AstraZeneca, FibroGen Marketed 2019 100 2033 01 Jun 2033 05 Nov 2023
Renal Anaemia ROW (0% US) Astellas Pharma, AstraZeneca, FibroGen Marketed 2021 100 2033 01 Jun 2033 05 Nov 2023
Renal Anaemia US Astellas Pharma, AstraZeneca, FibroGen Filed 2022 5 2030 01 Jan 2031 05 Nov 2023

Credit Suisse Financial Forecast

Indication Region 2021 2022 2023 2024 2025 2026 2027 2028 2029 2030 Last Update
Renal Anaemia China 174 197 236 272 300 330 362 398 398 398 05 Nov 2023
Renal Anaemia Japan 23 18 22 25 27 30 33 36 40 44 05 Nov 2023
Renal Anaemia ROW (0% US) 1 5 15 17 19 20 22 23 26 30 05 Nov 2023
Renal Anaemia US 0 0 50 100 200 300 399 500 500 500 05 Nov 2023
Total 198 220 323 414 546 680 816 957 964 972

Scientific Summary

  • Adverse Events Occasional: Hypertension

Pharmacokinetics

Oral roxadustat pharmacokinetics and pharmacodynamics were not significantly affected by haemodialysis. Peak concentrations of endogenous plasma erythropoietin nearly trippled with a doubling of roxadustat dose. Cmax values, however, remained significantly less than the peak circulating plasma recombinant human erythropoietin (rhEPO) levels. Endogenous erythropoietin Cmax was less than 10% of rhEPO Cmax levels expected for dialysis patients receiving the U.S. mean dose [approximately 8000U] of synthetic source rhEPO [167] .

Adverse Events

Anaemia of chronic disease in non-haemodialysis patients

No serious adverse events were attributable to roxadustat, and the frequency of adverse events were consistent with what would be expected in the CKD population, in a phase IIb study in 145 patients with anaemia and stage 3 or 4 chronic kidney disease (CKD) not on dialysis. The most common adverse events that occurred in > 5% patients on roxadustat were nausea, diarrhoea, constipation, vomiting, peripheral oedema, urinary tract infection, nasopharyngitis, sinusitis, dizziness and headache. Other adverse events included hypertension, which was reported in 7% of roxadustat recipients, a rate well below what has been reported for similar patient populations treated with erythropoiesis-stimulating agents (ESA) and the control arms of such studies. Hypertension and elevated platelet counts are associated with CKD and ESA therapy. In the study, significant mean reductions from baseline in mean arterial pressure were observed (-2.6 mmHg; p = 0.03) following treatment with roxadustat (90% of patients required antihypertensives prior to study start). In addition, platelet counts were significantly reduced from baseline (p < 0.01) and maintained within the normal range [77] [79] [78] [76] .

In the phase III FGCL-4592-808 trial in 154 evaluable patients, frequent treatment-emergent serious adverse events were synonymous with those typically observed among patients with chronic kidney disease [63] [66] .

Data from a phase III trial showed that the most common treatment emergent adverse events (TEAEs) associated with roxadustat were nasopharyngitis, back pain, diarrhoea, nausea, vomiting, catheter site infection, abdominal pain, conjunctivitis, constipation and pruritus [99] .

In phase III trial roxadustat was well tolerated and the safety profile was consistent with previous studies both in dialysis and non-dialysis patients. In both patient groups, the most common TEAEs were nasopharyngitis, shunt stenosis, diarrhoea, contusion, and vomiting. New or worsening retinal haemorrhage occurred in 32.4% of patients receiving roxadustat and 36.6% of patients receiving darbepoetin alfa during treatment as evaluated by blinded review of colour fundus photography images. There weren't any clinically meaningful changes in retinal thickness evaluated with OCT were observed throughout the treatment, in either of the groups. There wasn't any increased risk of ophthalmological abnormalities including retinal hemorrhages in patients treated with roxadustat compared to darbepoetin alfa [99] [100] [101] .

Roxadustat was generally well tolerated in a placebo-controlled phase IIa trial conducted in 116 non-dialysis patients with anaemia and stage 3 or 4 CKD. No serious, drug-related adverse events were observed. Compared with placebo, roxadustat was associated with a reduction in serum hepcidin, which is elevated with inflammation and restricts iron bioavailability. No changes in serum iron levels were observed following roxadustat treatment; this contrasts with literature reports for epoetin alfa whereby levels are lowered in the absence of supplementary iron therapy [12] . Diarrhoea (9.1%), headache (6.8%), back-pain (4.5%), fatigue (4.5%) and hyperkalemia (4.5%) were the most common adverse events associated with roxadustat [84] .

In a phase II trial in 107 patients with CKD having anaemia, roxadustat was well tolerated, without any deaths and major adverse cardiovascular events reported for roxadustat-treated patients [73] [74] .

Six weeks of oral roxadustat was generally well tolerated in 56 end-stage renal disease patients on haemodialysis according to interim findings from an ongoing, open-label, randomised, phase II trial. No notable cardiovascular or thrombotic adverse events were observed. Patients were grouped based on responsiveness to prior maintenance rhEPO (hyperresponsive, hyporesponsive, or normoresponsive). Hyperresponders stable on previous maintenance rhEPO were randomised to 6 weeks of intravenous rhEPO (control) or roxadustat, thrice-weekly, at 1.0, 1.5, or 2.0 mg/kg/dose. The dosing period was followed by an 8-week safety assessment period, during which all patients received IV rhEPO and were allowed to receive IV and oral iron [167] .

In a randomised, double-blind, placebo-controlled phase II trial of roxadustat (low and high dose cohorts) in 91 non-dialysed Chinese patients with anaemia and CKD, the incidence of adverse events similar across all groups. No serious cardiovascular adverse events were reported in the roxadustat groups [87] .

In a phase II study in 130 patients with CKD, which are on dialysis, roxadustat was well tolerated, with one death reported in a subject who suffered from bacterial pneumonia and thromboembolism, which was unrelated to roxadustat. No deaths were reported in the other treatment arms [73] [111] .

Roxadustat was well tolerated in maintaining and/or correcting haemoglobin given in subjects with End Stage Renal Disease on maintenance haemodialysis. Treatment-emergent adverse events were reported in 63 percent of all patients in the safety population. The nature and severity of the adverse events was typical for patients undergoing dialysis. The phase II randomised, open-label, active-comparator trial enrolled 144 patients [118] [116] .

In the phase III ALPS trial, the incidences of treatment-emergent adverse events were comparable between the groups (roxadustat: 87.7%, placebo: 86.7%). The results were obtained from the analysis of 594 patients randomised to receive roxadustat (n=391) and placebo (n=203) [3] [58] .

In the phase III DOLOMITES study the overall incidence of treatment emergent adverse events between roxadustat and darbepoetin alfa (91.6% and 92.5%, respectively) were comparable. A non-confirmatory analysis of adjudicated major adverse cardiovascular event (MACE)/MACE plus hospitalized unstable angina and hospitalized congestive heart failure (MACE+) outcomes showed HR point estimates of 0.81 (95% CI: 0.52, 1.25) and 0.90 (95% CI: 0.61, 1.32). The trial enrolled 616 patients [69] [70] .

Anaemia of chronic disease in haemodialysis patients

In the phase III HIMALAYAS trial, in patients with anaemia due to end-stage renal disease who are on dialysis, the safety profile of roxadustatwere consistent with results observed in previous roxadustat studies. Hypertension, diarrhoea and muscle spasms were the most frequently observed adverse events [110] [109] .

Anaemia of myelodysplastic syndrome patients

Updated results from a phase III MATTERHORN trial showed that roxadustat plus BSC was well-tolerated. Percentages of patients with TEAEs of any grade, serious TEAEs, and TEAEs leading to treatment discontinuation were similar across arms. Six deaths occurred on study roxadustat: pneumonia [n=2], acute myocardial infarction and ischemic stroke [n=1], multiorgan failure [n=1]; PBO: urosepsis [n=1], disease progression [n=1]). Three patients (all in roxadustat arm) progressed to acute myeloid leukemia [126] . Updated results from phase III trial demonstrated that the adverse event profile of roxadustat that was observed in the preliminary safety analysis was generally consistent with previous findings [125] . In a phase III trial roxadustat treatment was well tolerated in patients with anaemia with lower risk myelodysplastic syndrome (LR-MDS). Six patients showed eight treatment-emergent SAEs, but none of it was fatal [123] [122] .

Chemotherapy-induced aneamia

Phase II

In a phase II WHITNEY trial which evaluated the efficacy and safety of roxadustat in patients with non-myeloid malignancies with chemotherapy induced anaemia, demonstrated the overall safety profile to be consistent with the patient population under study. Overall, 92% of patients experienced an adverse event (AE) where most were consistent with the underlying malignancies and chemotherapy regimens used. The incidence of deep vein thrombosis was 15.2% (n = 14) and pulmonary embolism was 9.8% (n = 9). There were 17 deaths (18.5%) during the study. No AE were attributed to roxadustat, with most associated with disease progression [137] [135]

Pooled analysis:

Updated results from pooled analysis conducted across phase III programme to assess cardiovascular safety showed that the risk of MACE, MACE+ and all-cause mortality in roxadustat patients was comparable to placebo. A 30% lower risk of MACE and 34% lower risk of MACE+ was seen in incident dialysis (ID) patients treated with roxadustat compared with those taking epoetin alfa, with a trend towards lower all-cause mortality for roxadustat relative to epoetin alfa. In dialysis-dependent (DD) patient population there were no reports of increased risk of MACE and all-cause mortality and a lower risk of MACE+ compared to epoetin alfa based on a reference non-inferiority margin of 1.3. Risk of MACE+ was 14% lower in roxadustat-treated patients than in those receiving epoetin alfa. Earlier reported results demonstrated no clinically significant difference in MACE/MACE+ between roxadustat and placebo in the non-dialysis-dependent (NDD) patients. In incident dialysis population, MACE/MACE+ analyses showed that patients on roxadustat demonstrated superiority to epoetin alfa in the time to first MACE+. In the MACE analysis, there was a trend toward reduced risk for patients on roxadustat, compared to epoetin alfa. In dialysis-dependent population, MACE/MACE+ analyses demonstrated no clinically significant difference between roxadustat and epoetin alfa. In addition, in intent-to-treat (ITT) population in NDD-CKD patients, roxadustat showed comparable MACE and MACE+ events with placebo, based on a reference non-inferiority margin of 1.3. In a post hoc subgroup analysis with baseline eGFR = 15, roxadustat treated patients showed one-year decline in eGFR (-2.8) which was significantly less than that in placebo treated patients (-4.4), with a treatment difference of 1.6 mL/min/1.73m2 (p < 0.0001). The analysis was carried out for 9 776 patients across six phase III global trials (OLYMPUS, ANDES, ALPS, HIMALAYAS, SIERRAS, and ROCKIES) [51] [52] [162] [165] [164] .

In the OLYMPUS trial, the safety findings are generally consistent with the non-dialysis-dependent (NDD) chronic kidney disease patient population. The most common adverse events reported with roxadustat versus placebo were End stage kidney disease (ESKD) (21.0% vs 20.5%), urinary tract infection (12.8% vs 8.0%), pneumonia (11.9% vs 9.4%), and hypertension (11.5% vs 9.1%). Additional serious adverse events reported were azotemia, sepsis, acute kidney injury and hyperkalemia [3] [48] [50] .

In the ROCKIES trial, adverse events with roxadustat were generally similar to those seen in patients treated with epoetin alfa and commonly found in dialysis-dependent chronic kidney disease patients. The most frequently reported adverse events were diarrhea, hypertension, pneumonia, headache and arteriovenous fistula thrombosis. Additional serious adverse events reported were sepsis and acute myocardial infarction [48] [49] .

Results from two analyses of pooled data from the roxadustat global phase III development program, examining associations between the achieved hemoglobin (Hb) levels and cardiovascular outcomes of both non-dialysis-dependent (NDD) and dialysis-dependent (DD) patients with anemia of chronic kidney disease (CKD), showed that Major Adverse Cardiovascular Events (MACE; all-cause mortality, myocardial infarction, and stroke) and MACE+ (MACE plus heart failure or unstable angina requiring hospitalization) rates were highest when Hb was less than 8 g/dL, decreased as Hb increased, and were lowest when Hb levels were greater than or equal to 10 g/dL [39] .

Pharmacodynamics

Summary

Phase II:

In a phase IIb study in anaemic patients with CKD, treatment with roxadustat resulted in decrease in the levels of hepcidin, by 16.9% (p = 0.004), and total cholesterol, by a mean (±SD) of 26 (±30) mg/dl (p < 0.001), after 8 weeks of therapy [77] [76] .

Preclinical:

Abnormally high levels of hepcidin (a hormone that regulates the availability of iron for erythropoiesis) were downregulated by roxadustat to normal levels in an experimental model of inflammation-induced anaemia. The compound also alleviated microcytosis and hypochromia and corrected anaemia in this model [150] .

Red blood cell production was stimulated and anaemia corrected dose-dependently in rats with 5/6 nephrectomy that received roxadustat [168] .

Therapeutic Trials

Anaemia of chronic kidney disease (CKD) in non-dialysis patients

Early results from the phase III FGCL-4592-808 trial in 154 evaluable patients, showed that the trial met its primary endpoint, when the patients treated with roxadustat displayed a mean Hb increase of 1.9g/dL from baseline (8.9g/dL), over a period of eight weeks of treatment (7-9 weeks), as compared with a mean change in Hb of -0.4g/dL (from 8.9g/dL baseline) in the placebo arm (p<0.001). After 8 weeks, 84% (85/101) of patients in the drug arm achieved Hb response (an increase of 1g/dL from baseline), as compared with 0.0% (0/50) (p<0.00001) for the placebo arm, with a between-group difference of 84 percentage points (95% CI: 75- 91). A higher percentage of roxadustat-treated patients achieved average hemoglobin level of ≥10 g/dL at Weeks 7–9, with 67% patients in the roxadustat group, relative to 6% in the placebo group, for a between-group difference of 61 percentage points (95% CI: 47-72). At week 9, patients in roxadustat group, reported a greater mean reduction in hepcidin of -56.14 (±63.40) (p < 0.0001), compared with -15.10 (±48.06) ng/ml (p = 0.17) in the placebo group (p < 0. 0001 between groups), for a between-group difference of -49.77ng/mL (95% CI, -66.75 to -32.79). The decline from baseline in LDL cholesterol in the roxadustat arm were higher (-25.3mg/dL) than the placebo arm (-5.8mg/dL, with a between-group difference of -21.2mg/L (-0.5 mmol/L; 95% CI: -0.8 to -0.3). In these patients initially randomised to the roxadustat group (n=87), maintenance of efficacy was observed. The mean haemoglobin at weeks 23-27 was maintained at +1.9g/dL above baseline, with 84% of the patients achieving haemoglobin ≥11.0g/dL during the 26-week treatment period. In the patients crossing over from the placebo group (n=44), anaemia correction was displayed by achievement of a 2g/dL hike in haemoglobin from baseline, averaged over weeks 23-27, wherein 72% of the patients achieved haemoglobin ≥11g/dL during the treatment period [63] [64] [8] [66] .

Results from a phase III trial in chemotherapy induced anaemia demonstrated that the LSM (95% 2-sided confidence interval [CI]) change from baseline to Weeks 9‒13 in Hb concentration was 17.1 (13.58, 20.71) g/L with roxadustat and 15.4 (11.34, 19.50) g/L with rHuEPO-α. The lower bound of the 1-sided 97.5% CI for the treatment difference (‒3.4 g/L) was greater than the predefined non-inferiority margin of ‒6.6 g/L, establishing non-inferiority. Results were supported by key secondary endpoints [134] [133] .

In the phase III ALPS trial, superiority of roxadustat versus placebo was demonstrated for both primary efficacy endpoints of Hb response [odds ratio = 34.74, 95% confidence interval (CI) 20.48–58.93] and change in Hb from BL [roxadustat – placebo: +1.692 (95% CI 1.52–1.86); both P < 0.001]. The superiority of roxadustat was also observed for low-density lipoprotein cholesterol change from BL, and time to first use of rescue medication (both P < 0.001). The results were obtained from the analysis of 594 patients randomised to receive roxadustat (n=391) and placebo (n=203) [3] [58] .

Results from the phase III DOLOMITES study showed that the trial met its primary endpoint and demonstarted non-inferiority of roxadustat to darbepoetin in correction and maintenance of hemoglobin levels during the first 24 weeks of treatment (89.5% vs 78.0%; difference 11.51% [95% CI 5.66%, 17.36%]). The superiority of roxadustat compared with darbepoetin alfa was demonstrated by a decrease in low-density lipoprotein cholesterol with a least square mean (LSM) difference of –0.403 mmol/L (95% CI –0.510, –0.296; [P < 0.01]) and in time to first intravenous iron use with a hazard ratio (HR) of 0.45 (95% CI: 0.26, 0.78; [p = 0.004]). The non-inferiority of roxadustat to darbepoetin alfa was demonstrated for mean arterial pressure with a LSM difference of –0.372 mmHg (95% CI: –1.587, 0.842) and time to occurrence of hypertension (HR = 0.83; [95% CI: 0.56, 1.22]). The trial enrolled 616 patients [69] [70] .

Results from a phase III trial showed to maintain hemoglobin (Hb) levels within the target Hb range in both ESA-conversion patients and ESA-naïve patients. The Hb maintenance rate, measured as the proportion of subjects with average Hb levels within the target Hb range of 10.0 to 12.0 g/dL for Weeks 18 to 24, was 92.3% in ESA-naïve and 74.4% in ESA-conversion patients and the mean Hb levels were 11.05 g/dL and and 10.93 g/dL, respectively. At weeks 18-24, the maintenance rates of patients with at least one Hb value were 92.3% (95% CI: 64.0, 99.8; ESA Naive) and 86.5% (95% CI: 71.2, 95.5; ESA Conversion). The cumulative response rate for both Hb thresholds was 100.0% in the ESA Naive Group. The mean (SD) rate of rise in Hb levels in the ESA Naive group was 0.193 (0.203) and 0.556 (0.408) g/dL/week from Week 0 to Week 4 with roxadustat 50mg and 70mg, respectively. The trial enrolled 56 patients with chronic kidney disease [99] [106] [105] .

In phase III trial of roxadustat in hemodialysis-dependent chronic kidney disease (CKD) patients with anaemia, roxadustat was observed to be superior to darbepoetin alfa in decreasing low-density lipoprotein cholesterol with a least square mean (LSM) difference of -0.403 mmol/L (95% CI -0.510, -0.296; [P<0.01]) and superior in time to first intravenous iron use with a hazard ratio (HR) of 0.45 (95% CI: 0.26, 0.78; [P=0.004]). Mean arterial pressure change from baseline to weeks 12-28 with a LSM difference of -0.372 mmHg (95% CI: -1.587, 0.842) was noted. Time to occurrence of hypertension was observed to be HR 0.83 (95% CI: 0.56, 1.22). Earlier results showed that average hemoglobin (Hb) levels were effectively maintained at 10.99 g/dL at week 18 to 24 in roxadustat-treated hemodialysis patients previously treated with erythropoiesis-stimulating agents (ESAs). The primary endpoint of change in average Hb levels from baseline to week 18 to 24 was -0.04 g/dL and -0.03 g/dL in the roxadustat-treated group and in the darbepoetin-treated group, respectively. The non-inferiority of roxadustat to darbepoetin alfa in change of average Hb from baseline was confirmed as the lower bound of the 95% confidence interval (-0.18, 0.15) of the treatment difference was greater than the pre-specified non-inferiority margin (-0.75 g/dL). The Hb maintenance rates were reported as 79.3% (95% CI: 72.0, 85.5; roxadustat) and 83.4% (95% CI: 76.5, 89.0; darbepoetin alfa). At weeks 18-24, the percentage of patients with at least one Hb value maintained at Hb 10-12 g/dL were 95.2% (95% CI: 89.8, 98.2; roxadustat) and 91.3% (95% CI: 85.3, 95.4; darbepoetin alfa). The trial enrolled 303 patients with chronic kidney disease. Serum iron, ferritin, and TSAT were clinically stable in patients treated with roxadustat; and transferrin and TIBC increased through week 4 and then remained stable. There weren't any remarkable changes in iron parameters with darbepoetin alfa [98] [99] [99] [100] [101] .

In a randomised, placebo-controlled phase IIa trial roxadustat 0.7, 1.0, 1.5, or 2.0 mg/kg increased Hb levels in a dose-related manner within 14 to 25 days, with 30% Hb responders observed at 0.7 mg/kg to 100% at 2 mg/kg. The median time to response ranged from 42 days (1 mg/kg) to 14 days (2 mg/kg) in the 96 evaluable patients [84] .

A phase II trial in 107 CKD patients, which were not on dialysis, met its primary endpoint of demonstrating dose-dependant change in haemoglobin (Hb) increase, over the first six weeks of treatment as well as anaemia correction and Hb maintenance over the 24-week period. Roxadustat treatment led to a mean rate of Hb increase of 0.200, 0.453, and 0.570 g/dL per week (50mg, 70mg, 100mg, respectively), as measured over the first six weeks of the study, when compared with a mean Hb decrease of 0.052 g/dL per week in subjects receiving placebo. Haemoglobin correction was demonstrated by 93.8% of roxadustat-treated subjects. While, in placebo arm hemoglobin response was achieved in 14.8% of the subjects [74] [73] .

Median time to response was 21 days following treatment with roxadustat, 1.5 mg/kg and 2.0 mg/kg, in a phase IIa trial conducted in 117 non-dialysis patients with anaemia and stage 3 or 4 CKD. The corresponding historical value for usual starting doses of intravenous epoetin alfa and darbepoetin alfa is 49 days. All recipients of the 2 mg/kg dose (twice- and thrice-weekly administration), the highest dose level tested, achieved Hb increases of at least 1 g/dL from baseline. Peak levels of endogenous erythropoietin were also lower after dosing with roxadustat 1 mg/kg when compared with data from another trial of maintenance intravenous epoetin alfa (100 vs 400-750 mIU/mL) [12] . Compared to placebo, patients treated with roxadustat experienced significant decreases in total cholesterol (p<0.0001) and LDL-cholesterol (p<0.0001) at 8 weeks. The relative proportion of HDL-cholesterol to LDL-cholesterol increased significantly in the roxadustat-treated patients, vs placebo (p<0.02) [87] .

Previously reported interim results showed that treatment with roxadustat was associated with 96% of patients experiencing an increase in haemoglobin (Hb) of at least 1 g/dL, and 93% experiencing an Hb response, overall. Response rates were 83%, 100%, 91% and 96% in arms A (roxadustat thrice-weekly with dose adjustments), B (weight-adjusted roxadustat thrice-weekly followed by twice-weekly), C (fixed-dose roxadustat at 50mg thrice-weekly followed by dose adjustments) and D (fixed-dose roxadustat at 100mg thrice-weekly followed by dose adjustments), respectively; response was defined as an increase in Hb of at least 1 g/dL and an absolute Hb concentration of at least 11 g/dL for arms A and B (treated for 16 weeks) and 10.5 g/dL for arms C and D (treated for 24 weeks). Data was analysed from a total of 96 patients. Importantly, the study revealed that treatment success was not dependent on a patient's iron status at study entry [78] .

Positive results from a phase IIb study of roxadustat in anaemic patients with CKD showed that, out of the 143 patients evaluable, 92% achieved a haemoglobin response defined as a hemoglobin increase of > 1.0 g/dl from baseline and hemoglobin of > 11.0 g/dl by the end of treatment. The treatment duration was up to 16 weeks for 47 patients, and up to 24 weeks for 96 patients [77] . Preliminary results reported earlier showed that administration with roxadustat thrice weekly (n = 39) resulted in a significant mean reduction from baseline to the end of treatment in systolic (-5.3 ± 2.4 mmHg, p = 0.03) and diastolic (-2.5 ± 1.1 mmHg, p < 0.03) blood pressure. Additionally, there was a significant mean increase in systolic blood pressure at the end of treatment compared with the follow-up period (3.3 ± 1.5 mmHg, p < 0.04). Mean baseline systolic and diastolic blood pressure levels were 132.5 ± 2.3 mmHg and 68.6 ± 1.2 mmHg. A total of 145 patients with stage 3-4 chronic kidney disease (CKD) and anaemia were randomised to receive roxadustat for 16 or 24 weeks, using a range of dosages [79] [76] .

In a randomised, double-blind phase II trial in 91 non-dialysed Chinese patients with anaemia and CKD, roxadustat corrected Hb levels in a dose-dependent manner. After 8 weeks of treatment, patients showed mean maximum Hb increases from baseline of 2.6g/dL, 1.8g/dL and 0.7g/dL in the high dose, low dose and placebo groups, respectively (p<0.0001). In these respective groups, 87%, 80% and 23% of patients achieved Hb increases of ≥1g/dL from baseline (p<0.0001). Also in these respective groups, 71%, 50% and 3% of patients achieved target Hb of ≥11g/dL (p<0.0001) [87] .

The phase III ANDES trial met primary endpoint for meeting the US and the EU regulatory requirements. In non-dialysis-dependent (NDD) chronic kidney disease (CKD) patients, US primary efficacy endpoint was reached in which roxadustat (n=616) showed superior effect in mean Hb change from baseline to the average over weeks 28-52 compared with placebo (n=306) (2.00 vs 0.16 g/dL, respectively, p < 0.0001). The trial also met EU primary efficacy endpoint in which a Hb response in the first 24 weeks (defined as achieving a Hb level of at least 11 g/dL and a Hb increase of at least 1 g/dL) was achieved in more number of roxadustat-treated patients (86.0%) than placebo (6.6%) (p=0.0007). In addition, The proportion of patients receiving rescue therapy at week 52 was smaller for roxadustat (8.9%) versus placebo (28.9%); hazard ratio, 0.19 (95% CI 0.14–0.28; P < .0001). Thus, the risk of rescue therapy was reduced by 81% post treatment with roxadustat (p < 0.0001) with reduction in the risk of blood transfusion by 74% (HR = 0.26) in the time to first blood transfusion during the first 52 weeks of treatment (p < 0.0001) [3] [72] [57] .

Anaemia of chronic kidney disease (CKD) in dialysis patients

In a phase III FGCL-4592-806 trial in 304 evaluable patients, roxadustat displayed greater mean change in haemoglobin (Hb) from baseline to weeks 23-27 of 0.8 g/dL (±1.1) as compared with epoetin alfa, (0.5 g/dL ±1.0) and was statistically non-inferior. Roxadustat increased transferrin, maintained serum iron, and attenuated decreases in TSAT versus epoetin alfa (all p<0.01). At week 27, the decline in LDL cholesterol was greater with roxadustat (both p < 0.0001). Roxadustat reduced hepcidin from baseline by a mean of 30.2 ng/ml (p = 0.003), compared to a reduction of 2.3 ng/ml in the epoetin alfa group (p = 0.12). Earlier, it was observed that the mean Hb increase in roxadustat arm was 0.75g/dL, as compared with 0.46g/dL (p=0.037), in the epoetin alfa arm, in PPS analysis. In subgroup analysis based on the baseline CRP levels, roxadustat demonstrated consistent efficacy in Hb control regardless of CRP levels without increase in roxadustat dose requirements, while epoetin alfa patients with elevated baseline CRP levels showed lower Hb response despite receiving higher average doses of epoetin alfa, compared to the doses patients with normal baseline CRP levels received. In the subgroup of inflamed patients (as measured by elevated CRP), mean change in Hb to weeks 23-27 were significantly higher in roxadustat than epoetin alfa (p=0.0034) [64] [8] [107] .

A phase II trial in 130 CKD patients, which were on dialysis, met its primary endpoint of demonstrating dose-dependant change in haemoglobin (Hb) increase, over the first six weeks of treatment as well as anaemia correction and Hb maintenance over the 24-week period. During weeks 18 to 24, average Hb levels achieved in the full analysis set were 10.31 g/dL (1.33 g/dL Hb increase), 10.20 g/dL (1.37 g/dL Hb increase), and 10.53 g/dL (1.57 g/dL Hb increase), respectively, in the roxadustat treatment arms, compared with 10.25 g/dL (1.42 g/dL Hb increase) in the darbepoetin arm [73] [111] .

In a randomised, open-label, dose-titration phase II study in patients of anaemia with chronic kidney disease, treatment with roxadustat led to 96% haemoglobin (Hb) response and increased mean Hb, regardless of baseline iron repletion status, C-reactive protein level, iron regimen, or dialysis modality within 7 weeks. In 55 patients the mean maximum Hb change from baseline (baseline Hb 8.3+1.0 g/dL), was 3.1 ±0.2 g/dL. Similar rates of increase in mean Hb over the 12-week treatment period and the mean Hb levels during the last four weeks were observed among patients receiving oral or intravenous iron (mean maximum Hb change of 3.4 to 3.5 g/dL). A mean maximum Hb increase of 2.8 g/dL was seen with roxadustat therapy in the absence of any form of iron supplementation. The trial enrolled 60 patients [113] .

There were increases in Hb levels in patients with anaemia and CKD in response to roxadustat therapy, according to preliminary results of a dose-escalation phase II trial. Twenty-nine such patients received, by oral administration, placebo (n = 8) or roxadustat at doses ≤120mg (n = 21) twice- or thrice-weekly for 4 weeks. Increases in Hb of ≥1 g/dL that were maintained for 2-4 weeks after treatment cessation were noted in 5 of 8 (63%) patients who received roxadustat at doses of 40-120mg, whereas 0 of 4 placebo recipients had a similar Hb increase [168] .

In a subgroup analysis of a phase II trial, the response to roxadustat in patients with end stage renal disease on peritoneal dialysis was compared with results from patients on haemodialysis. Increases in haemoglobin levels of 3.3 and 3.5 g/dL were observed in patients on peritoneal dialysis and haemodialysis, respectively. Both patient groups received oral but not intravenous iron supplementation [166] .

Six weeks of oral roxadustat maintained correction of Hb, in the absence of intravenous iron supplementation, and led to marked, dose-dependent decreases in hepcidin compared with levels achieved with recombinant human erythropoietin (rhEPO) in end-stage renal disease patients on haemodialysis. These were the findings from an interim analysis of 56 patients from an ongoing, randomised, phase IIb trial. Stable patients were grouped based on responsiveness to prior maintenance rhEPO (hyperresponsive, hyporesponsive, or normoresponsive). Hyperresponders stable on previous maintenance rhEPO were randomised to 6 weeks of intravenous rhEPO orroxadustat, thrice-weekly, at 1.0, 1.5, or 2.0 mg/kg/dose. The dosing period was followed by an 8-week safety assessment period, during which all patients received IV rhEPO and were allowed to receive IV and oral iron. Following the initial assessment in hyperresponders, evaluations will begin in patients classified as normoresponsive to maintenance rhEPO [167] .

Roxadustat maintained Hb levels among patients on hemodialysis, who were previously treated with and switched from epoetin alfa over two time periods of 6 and 19 weeks. In the first part of the study, which lasted for 6 weeks, lowest dose of roxadustat (1.0 mg/kg per dose thrice weekly) maintained Hb at a level comparable to epoetin alfa (44% vs 33%). The drug achieved greater Hb response than epoetin alfa at a dose of 1.5 mg/kg or greater, with a pooled response at 6 weeks of 79% compared with 33% in those receiving epoetin alfa. In the second part of the study, the mean difference between Hb values in patients receiving roxadustat and epoetin alfa was -0.03 g/dL (95% CI -0.39 to 0.33 g/dL). The primary endpoint (Hb level > 11.0 g/dL) was achieved in 51% of subjects receiving roxadustat over the last four weeks of the 19-week treatment period compared with 36% of those receiving epoetin alfa. During the last 7 weeks of therapy, roxadustat maintenance dose requirements were not correlated with levels of the inflammatory parameter C-reactive protein (CRP), even in subjects with average CRP levels elevated above upper limit of normal [(ULN=5 mg/L): n=26/49 (53.1%), median 19.3 mg/L, range 5.5-71.7 mg/L (up to 14x ULN)]. In the roxadustat-treated subjects, Hb was maintained within physiologic levels of endogenously produced erythropoietin while reticulocytes were produced and continued to demonstrate stable and adequate Hb concentration in the absence of intravenous iron. Finally, decreases in cholesterol and hepcidin were observed during roxadustat treatment. The phase II randomised, open-label, active-comparator trial enrolled 144 patients [118] [116] .

In a phase II, open label, randomised trial conducted in in 87 Chinese dialysis-dependent CKD patients who had previously been treated for anaemia, haemoglobin levels were maintained in 59.1%, 88.9% and 100% patients receiving low, medium and high doses of roxadustat, respectively (p = 0.008), compared with 50% of the epoetin alfa-treated subjects [89] [119] .

The phase III HIMALAYAS trial met primary endpoint for meeting the US and the EU regulatory requirements. In incident dialysis chronic kidney disease (CKD) patients, US primary efficacy endpoint was reached in which mean Hb change from baseline to the average over weeks 28-52 in roxadustat (n=522) arm was 2.57 g/dL vs. 2.36 g/dL in epoetin alfa arm (n=521) (LS: 0.18 g/dL; 95% CI: 0.08, 0.29). The non-inferiority criteria was met as the lower bound of the 95% CI was well above the non-inferiority margin of -0.75 g/dL, and superiority over epoetin alfa was also achieved (p = 0.0005). The trial also met EU primary efficacy endpoint in which roxadustat met the non-inferiority criteria compared with epoetin alfa. Responder rate in first 24 weeks in roxadustat group was 88.2% compared with 84.5% in the epoetin alfa arm. Lower bound of the 95% CI (-0.9%, 7.6%) of the treatment difference in responder rate was well above the non-inferiority margin of -15%. Roxadustat patients required lower average monthly intravenous iron use than epoetin alfa patients (p = 0.00028). Among patients treated with roxadustat the mean Hb increased from 8.4 g/dL to 11.0 g/dL vs. 8.4 g/dL to 10.8 g/dL in epoetin alfa-treated patients. The trial enrolled 1043 patients [110] [72] [109] .

The phase III SIERRAS trial met primary endpoint for meeting the US and the EU regulatory requirements. In stable dialysis chronic kidney disease (CKD) patients (n=741), US primary efficacy endpoint was reached in which mean Hb change from baseline to the average over weeks 28-52 in roxadustat arm was 0.39 g/dL vs. -0.09 g/dL in epoetin alfa arm (LS: 0.48 g/dL; 95% CI: 0.37, 0.59). The non-inferiority criteria was met in roxadustat arm as the lower bound of 95% CI was well above the non-inferiority margin of -­0.75 g/dL and superiority over epoetin alfa was also achieved (p < 0.0001). The trial also met EU primary efficacy endpoint in which mean Hb change from baseline to the average over weeks 28-36 in roxadustat arm was 0.54 g/dL vs. -0.02 g/dL in epoetin alfa arm (LS: 0.53 g/dL; 95% CI: 0.39, 0.67). The non-inferiority criteria was met in roxadustat arm as the lower bound of 95% CI was well above the non-inferiority margin of -­0.75 g/dL and superiority over epoetin alfa was also achieved (p < 0.0001). In addition, roxadustat treatment resulted in reduction in the risk of blood transfusion by 33% (HR = 0.26) compared with epoetin alfa (HR=0.67) in the time to first blood transfusion during the first 52 weeks of treatment (p=0.0337) [72] [108] .

In the phase III OLYMPUS trial, roxadustat demonstrated a statistically significant improvement in Hb levels from baseline, with a mean increase of 1.75g/dL averaged over weeks 28 to 52, compared with 0.40g/dL with placebo. Roxadustat also improved Hb levels from baseline in a subgroup of patients with elevated high-sensitivity C-reactive protein (hsCRP) levels of greater than 5 mg/L, with a statistically significant mean increase of 1.73g/dL, compared with 0.62g/dL with placebo, in anaemia in non-dialysis-dependent chronic kidney disease patients [3] [48] [50] .

In the phase III ROCKIES trial in anaemia in dialysis-dependent chronic kidney disease patients, roxadustat demonstrated a statistically significant improvement in Hb levels from baseline with a mean increase of 0.77g/dL averaged over weeks 28 to 52, compared with 0.68g/dL with epoetin alfa. Roxadustat also improved Hb levels from baseline in a subgroup of patients with elevated hsCRP levels of greater than 5 mg/L, demonstrating a statistically significant improvement with a mean increase of 0.80g/dL compared to 0.59g/dL with epoetin alfa. Patients treated with roxadustat used less monthly intravenous (IV) iron (mean = 59 mg) compared to those treated with epoetin alfa (mean = 91mg) from week 36 to the end of the study [48] [49] .

Chemotherapy-induced aneamia

Phase II

Results of a phase II WHITNEY trial which evaluated the efficacy and safety of roxadustat in patients with non-myeloid malignancies with chemotherapy induced anaemia showed that roxadustat increased hemoglobin in chemotherapy-induced anemia (CIA) regardless of tumor type and chemotherapy regimen. Patients were treated with roxadusta 2.0 mg/kg (n = 31) and 2.5 mg/kg (n = 61) starting doses, and 89 were assessed for efficacy. The maximum mean hemoglobin change from baseline without RBC transfusion was 2.47±1.51 g/dL and 2.52±1.54 g/dL in the 2.0 mg/kg and 2.5 mg/kg cohorts, respectively. Hemoglobin increased by 1.5 g/dL in 73% of patients and 2.0 g/dL in 61% of patients. Median time to 2.0 g/dL Hb increase was 71.0 days. Both cohorts had higher proportions of patients with a hemoglobin increase of 1, 1.5, or 2 g/dL at week 16 compared with baseline. Median time to 1 and 2 g/dL hemoglobin increase was shorter in patients who started on 2.5 mg/kg compared with 2.0 mg/kg doses (=1 g/dL: 30 vs 44; =2 g/dL 57 vs 105, respectively). Fewer patients required an RBC transfusion from week 5 to end of treatment, when starting on 2.5 mg/kg compared with 2.0 mg/kg doses (10.2% vs 20.0%). In addition, subgroup analyses based on major tumor and baseline chemotherapy types demonstrated efficacy of roxadustat at both starting doses [137] [135]

Pooled analysis:

Updated results from pooled analysis demonstrated increased both serum iron and iron-carrying capacity (transferrin) with simultaneously induction of erythropoiesis in patients with NDD-CKD after treatment with roxadustat. Mean estimated glomerular filtration rate (eGFR) was 20 ml/min/1.73 m2 in both roxadustat an placebo groups. Increase in mean Hb was observed from baseline (1.9 vs 0.2 g/dL) over 28-52 weeks. Overall, 2.1% of patients receiving roxadustat required intravenous iron compared to 4.8% of patients receiving placebo. Roxadustat reduced hepcidin and increased both transferrin and serum iron. Patients with the highest base line values showed saturation in reductions of ferritin and transferrin [93] . Earlier data from the pooled analysis demonstrated achievement of endpoint in NDD and DD patients, and in all individual phase III trials. Roxadustat demonstrated a statistically significant improvement in NDD patients from baseline in hemoglobin (Hb) levels, regardless of iron repletion, averaged over weeks 28 to 52 of 1.85 g/dL in patients treated with roxadustat compared to 0.13 g/dL with placebo arm, for an overall treatment difference of 1.72 g/dL (p<0.001). The rate of rescue therapy in the first year of treatment among patients treated with roxadustat was 8.9%. less than the one third of the rate of the placebo arm (31.1%; p < 0.0001); HR=0.19 (95% CI: 0.16, 0.23). The rate of red blood cell (RBC) transfusions required in the first year of treatment was also lower with roxadustat (5.2%) than placebo (15.4%) (p < 0.0001; HR=0.26) (95% CI: 0.21, 0.32). In the DD population roxadustat demonstrated a statistically significant mean increase from baseline in Hb levels averaged over weeks 28 to 52 with 1.22 g/dL in patients treated with roxadustat compared to 0.99 g/dL, for an overall treatment difference of 0.23 g/dL (p < 0.0001). Roxadustat was superior to epoetin alfa across patients regardless of inflammation status which categorised by the baseline CRP levels (CRP > 4.9 mg/L), demonstrating an improvement of 1.29 g/dL and 1.27 g/dL in Hb levels from baseline in patients with and without inflammation, respectively, compared to 0.96 g/dL and 1.05 g/dL with epoetin alfa. In both NDD and DD population, roxadustat was effective in raising Hb levels regardless of whether patients were iron-replete (i.e., shown to have sufficient stores of iron in their body, TSAT% = 20% and Ferritin = 100 ng/mL) at baseline. In NDD patients mean change of 1.94 g/dL from baseline with roxadustat in both iron-replete and non-replete subpopulations was observed, compared to 0.13 g/dL in iron-replete and 0.33 g/dL in non-replete patients receiving placebo. The analysis was carried in 8 127 patients [NDD (n = 4277) and DD (n = 3880)] from six phase III trials (OLYMPUS, ANDES, ALPS, HIMALAYAS, SIERRAS, and ROCKIES) [51] [52] [162] .

In pooled analysis data from three phase III trials, (HIMALAYAS, SIERRAS and ROCKIES), roxadustat was found to be non-inferior and superior in increasing the haemoglobin in both the all-dialysis patients as well as incident dialysis patients groups. Over weeks 28 to 52, the mean (SD) changes in hemoglobin from baseline, regardless of rescue therapy, were 2.12 (1.45) in the roxadustat group versus 1.91 (1.42) g/dl in the epoetin alfa group (least-squares mean difference: 0.22; 95% CI, 0.05 to 0.40; P = 0.0130). Data related to risks of MACE and MACE+ were similar as before. The results were obtained from 1530 patients with kidney failure incident to dialysis [3] . According to earlier results in all-dialysis pooled analysis, roxadustat also showed reduction in RBC transfusion when compared with epoetin alfa (EPO). The primary endpoint of mean Hb change from baseline (CFB) over weeks 28-52, was met for each individual study (both noninferior and superior) and was 1.21 in the roxadustat versus 0.95 g/dL in the EPO arms (difference 0.26 g/dL; 95% CI 0.20, 0.33) in the pooled analysis, also noninferior and superior (p < 0.0001). Transfusions received were less for roxadustat group than the EPO group (9.5% vs 12.8%, respectively; HR = 0.82; 95% CI 0.679, 0.997). Among all dialysis patients, comparing roxadustat with EPO, hazard ratio (HR) for myocardial infarction, and stroke events (MACE), was 0.96 (95% CI 0.82, 1.13) and for heart failure or unstable angina requiring hospitalization events (MACE+) was 0.86 (0.74, 0.98) (p = 0.028). Amongst the 1 526 incident patients, the HRs of MACE and MACE+ were lower in the roxadustat when compared with EPO arms, 0.70 (95% CI 0.51, 0.96; p = 0.029) and 0.66 (95% CI 0.50, 0.89; p = 0.005) [159] [109] [108] [49] .

Updated results from the pooled analysis three phase III trials, OLYMPUS, ANDES and ALPS demonstrated raise in hemoglobin levels in NDD-CKD patients with over 95% of patients achieving Hb ≥10 g/dL after 5 months of treatment. The cumulative percentage of patients with Hb≥10 g/dL for at least two consecutive visits was 38.3%, 75.5%, and 87.0% at 1, 2, and 3 months respectively and 96.4% at month 6. The cumulative percentage with confirmed Hb ≥10 g/dL was 99.0%, among patients still receiving roxadustat treatment at 12 months [92] . Earlier results from the pooled analysis from the three phase III trials, OLYMPUS, ANDES and ALPS, trials showed that across all studies, significant (p < 0.001) and consistent improvements in haemoglobin were observed with roxadustat compared with placebo that were maintained over time. Intravenous iron rescue therapy use was lower with roxadustat versus placebo [91] [50] [58] [57]

In pooled analysis data from six phase III trials (for up to four years of duration), in patients (n = 4 277) with non-dialysis-dependent (NDD) anaemia of 3-5 chronic kidney disease (CKD), roxadustat, markedly and significantly reduced transfusion risk versus placebo. The efficacy was consistent across all trials. Roxadustat also resulted in significant reduction of transfusion risk when compare with epoetin alfa (EPO) in DD CKD, however it varied within trials. Roxadustat reduced the risk of RBC transfusion by 74% versus placebo in NDD patients and by 18% versus epoetin alfa in DD patients [158] .

In pooled analysis conducted across three NDD-CKD studies, rate of eGFR decline was reduced by 38% in the roxadustat-treated patients versus placebo-treated patients in patients with baseline eGFR ≥15 mL/min/1.73 m2, with a treatment difference of 1.62 mL/min/1.73 m2 in eGFR change at 12 months from the baseline (p < 0.0001). Roxadustat also showed a statistically significant improvements from baseline to Week 12 in quality of life endpoints, including SF-36 Vitality subscale (p=0.0002), SF-36 Physical Functioning subscale (p=0.0369), FACT-AN Anemia subscale (p=0.0012), FACT-AN Total score (p=0.0056), and EQ-5D-SL VAS score (p=0.0005) compared with placebo in pooled results from three NDD-CKD studies. Roxadustat also demonstrated efficacy regardless of inflammation status as the mean achieved Hb levels and roxadustat dose requirements were not impacted by baseline c-reactive protein (CRP) levels in multiple phase III trials. In phase III SIERRAS trial, roxadustat dose requirements remained stable over time, while epoetin alfa dose requirements increased by 57% over 52 weeks in the epoetin alfa arm [165] .

Pooled analysis:

Results from three pivotal, randomized, phase III studies of roxadustat vs placebo NDD CKD populations and a phase III study of roxadustat vs darbepoetin alfa in NDD CKD were pooled. Treating 4 patients with roxadustat vs placebo for 1 year is estimated to avoid 1 RBC transfusion. Treating 7 patients with roxadustat vs placebo for 1 year is estimated to avoid 1 patient needing 1 RBC transfusion, and treating 37 patients with roxadustat vs placebo is estimated to avoid 1 patient needing IV iron. Rates of RBC transfusion (hazard ratio [HR]: 1.3 [95% CI 0.79, 2.11; p=0.3]) were comparable between roxadustat and darbepoetin alfa in the additional analyzed study, and a lower proportion of patients on roxadustat vs darbepoetin alfa required IV iron therapy use (HR: 0.45 [95% CI: 0.26, 0.78; p=0.004]). It was concluded that the number of patients needed to treat to prevent RBC transfusion were low and indicative of patient benefit. Roxadustat reduced rates of RBC transfusions and IV iron use compared to placebo [94] .

Anaemia of myelodysplastic syndrome patients:
Updated results from a phase III MATTERHORN trial showed that a high percentage of patients with LR-MDS and LTB were TI responders. Most patients (72.1% [101/140]) had IPSS-R low-risk disease and a transfusion burden of 2–4 pRBC units Q8W (92.1% [129/140]). Median (range) BL transfusion burden was 2.5 (1–10) pRBC units. Seventy patients (50.0%) received prior ESAs (98.6% [69/70] were ESA-refractory). Eighty-four patients (41/82 [50.0%] roxadustat, 43/58 [74.1%] PBO) completed 28 weeks of treatment, and 15 patients (6/82 [7.3%] roxadustat, 9/58 [15.5%] PBO) were continuing treatment. Median (range) treatment duration was 24.1 (1.1–28.0) weeks for the roxadustat arm and 28.0 (0.1–28.0) weeks for the PBO arm. A greater percentage of patients in the roxadustat arm compared with the PBO arm were TI responders (47.5% vs. 33.3%). This difference did not reach statistical significance (p=0.22) [126] . Updated results from phase III trial demonstrated that the proportion of patients who achieved red blood cell transfusion independence in the first 28 weeks was 47.5% for the roxadustat arm compared to 33.3% for placebo (p=0.217) [125] . In a phase III trial that evaluated roxadustat in the treatment of anaemia in patients with lower risk myelodysplastic syndrome (LR-MDS), nine patients (38%) achieved transfusion independence (TI) for at least 56 consecutive days within the first 28 weeks. Four patients showed continued TI for >20 weeks (one at 1.5 mg/kg dose level and three at 2.5 mg/Kg dose-level). TI was achieved by one additional patient after the initial 28-week dosing period at a dose-level of 3.5 mg/kg (starting dose 2.0 mg/kg). A ≥50% reduction in RBC units in any 8-week period was achieved by A total of 14 patients (58%), compared to baseline (range of 2-4 RBC units in 8 weeks before dosing). Twelve of these patients were at ≥ 2.5 mg/kg dose level when achieving a 50% reduction in transfusion without need for IV iron [123] [122] .

Pooled analysis from three phase III trials OLYMPUS, ANDES and ALPS trials met the primary endpoint (mean Hb CFB over weeks 28-52) for each individual trial (both noninferior and superior, all p-values were at least = 0.001) and was +1.85 (± 0.94) g/dL in the pooled roxadustat vs +0.13 (± 1.01) g/dL placebo groups (p=0.0001). In the first 52 weeks, roxadustat patients had a lower risk of rescue therapy, hazard ratio (HR) (95% CI) = 0.19 (0.16, 0.23; 81% reduction, p=0.0001), with RBC transfusion HR (95% CI) = 0.26 (0.21, 0.32; 74% reduction, p=0.001). Attenuation of eGFR progression among patients with BL eGFR=5 (N=2456; roxadustat v. placebo in eGFR to 52 wks) was 1.6 mL/min, p=0.0001; reduced eGFR decline by 36% (-2.8 vs. -4.4). Early LDL reduction continued through week 28, p=0.0001. In the intent to treat population, HR for MACE events was 1.08 (95% CI 0.94, 1.24) for roxadustat compared with placebo, and 1.04 (95% CI 0.91, 1.18) for MACE+. In the subgroup with BL eGFR 10 (n=3431), MACE HR (95% CI) = 0.99 (0.84, 1.16) and MACE+ =0.98 (0.85, 1.14) for roxadustat v. placebo. Roxadustat patients had significantly longer MACE- and MACE+-free survival on treatment than placebo (p=0.0001) [56] [50] [57] [58] .

Future Events

Expected Date Event Type Description Updated
30 Jun 2024 Regulatory Status FibroGen expects NMPA decision for Chemotherapy induced anaemia in mid 2024 (9403309) 10 Nov 2023
30 Nov 2023 Trial Update Astellas Pharma plans phase-III trial for Anaemia (In Children, In adolescents) in November 2023 (PO) (NCT05970172) (700366057 ) 26 Dec 2023
31 Dec 2021 Regulatory Status AstraZeneca announces intention to submit regulatory application for anaemia of myelodysplastic syndrome in 2021 [161] 17 Aug 2020
15 Jul 2021 Regulatory Status The Cardiovascular and Renal Drugs Advisory Committee (CRDAC) of the US FDA to hold Advisory Committee Meeting on roxadustat NDA in July 2021 [3] 16 May 2021
30 Jun 2021 Regulatory Status FibroGen expects decision of the European Medicines Agency (EMA) for review of the MAA of roxadustat in Anaemia, by mid-2021 [157] 25 Aug 2021
20 Mar 2021 Regulatory Status FDA assigns PDUFA action date of 20/03/2021 for roxadustat for Anaemia in USA (PO) [24] 05 Mar 2021
31 Dec 2020 Regulatory Status AstraZeneca expects regulatory decision for Anaemia in the US in Q4 2020 (3516870) 20 Nov 2020
30 Jun 2020 Regulatory Status Astellas Pharma announces intention to submit MAA to the EMA for dialysis and non dialysis dependent CKD Anaemia in the first half of 2020 [17] 22 May 2020
07 May 2020 Regulatory Status FibroGen announces intention to submit Marketing Authorization Application for Anaemia in Europe in second quarter of 2020 [160] 05 Mar 2021
31 Dec 2019 Regulatory Status AstraZeneca and FibroGen expect to launch roxadustat in China in the second half of 2019 [29] 21 Nov 2019
31 Dec 2019 Regulatory Status FibroGen expect approval of roxadustat for Anaemia in dialysis-dependent chronic kidney diseases in Japan in the second half of 2019 [163] 23 Sep 2019
31 Dec 2019 Regulatory Status FibroGen announces intention to submit NDA to US FDA for Anaemia by Q4 of 2019 [96] 27 Dec 2019
30 Sep 2019 Regulatory Status FibroGen expect approval of roxadustat for Anaemia in non-dialysis-dependent chronic kidney diseases in China in the third quarter of 2019 [163] 05 Mar 2020
01 Jun 2019 Trial Update Astellas Pharma plans a phase I trial for Healthy volunteers (PO) (NCT03960489) (700307734) 22 Jul 2019
31 Dec 2018 Regulatory Status Astellas announces intention to submit NDA for Anaemia (associated with dialysis-dependent CKD) in Japan in 2018 [47] 05 Oct 2018
31 Mar 2018 Trial Update FibroGen plans a phase II/III trial for Anaemia (associated with Myelodysplastic syndrome) in China (PO) (NCT03303066) in first quarter of 2018 [129] 29 May 2018
30 Sep 2017 Trial Update FibroGen plans a pivotal phase III trial for Anaemia (associated with Myelodysplastic syndrome) in USA in third quarter of 2017 [129] 14 Nov 2017

Development History

Event Date Update Type Comment
26 Feb 2024 Licensing Status FibroGen and AstraZeneca terminates the license agreement for Roxadustat from AstraZeneca in the United States and other AstraZeneca territories, excluding China and South Korea [2] Updated 28 Feb 2024
09 Dec 2023 Scientific Update Efficacy and adverse events data from a phase III MATTERHORN trial in Anaemia presented at the 65th American Society of Hematology Annual Meeting and Exposition (ASH-Hem-2023) [126] Updated 31 Jan 2024
20 Nov 2023 Phase Change - III Phase-III clinical trials in Anaemia (In infants, In children, In adolescents) in Romania (PO) (NCT05970172) Updated 26 Dec 2023
06 Nov 2023 Regulatory Status FibroGen expects NMPA decision for Chemotherapy induced anaemia in mid 2024 [130] Updated 10 Nov 2023
05 Nov 2023 Financial Update Credit Suisse financial data update Updated 05 Nov 2023
20 Oct 2023 Scientific Update Efficacy data from a phase III trial in Chemotherapy-induced anaemia presented at the 48th European Society for Medical Oncology Congress (ESMO-2023) [134] Updated 07 Dec 2023
30 Sep 2023 Regulatory Status National Medical Products Administration China accepts the sNDA for roxadustat for Chemotherapy-induced anemia for review [130] Updated 01 Feb 2024
14 Aug 2023 Trial Update FibroGen terminates a phase III MATTERHORN trial for Anaemia in USA, Australia, Germany, Belgium, Israel, Italy, South Korea, Russia, United Kingdom, Denmark, Canada, France, India, Poland, Turkey and Spain as the study did not meet its primary efficacy endpoint (NCT03263091) Updated 25 Aug 2023
07 Aug 2023 Phase Change - Preregistration Preregistration for Chemotherapy-induced anaemia in China (PO) prior to August 2023 [132] Updated 09 Aug 2023
01 Aug 2023 Trial Update Astellas Pharma plans phase-III trial for Anaemia (In Children, In adolescents) in November 2023 (PO) (NCT05970172) Updated 26 Dec 2023
22 Jun 2023 Trial Update FibroGen completes a phase III MATTERHORN trial for Anaemia in USA, Australia, Germany, Belgium, Israel, Italy, South Korea, Russia, United Kingdom, Denmark, Canada, France, India, Poland, Turkey and Spain (NCT03263091) Updated 25 Aug 2023
18 May 2023 Regulatory Status FibroGen announces intention to submit sNDA to the National Medical Products Administration (NMPA) China for Chemotherapy-induced anaemia [131] Updated 25 May 2023
05 May 2023 Scientific Update Safety and efficacy data from a phase III MATTERHORN trial in Myelodysplastic syndromes (MDS) released by FibroGen [125] Updated 09 May 2023
21 Apr 2023 Trial Update FibroGen completes a phase III trial for Chemotherapy Induced Anemia in (In Adults, In the elderly) China (PO)(NCT05301517) Updated 21 Jun 2023
08 Feb 2023 Trial Update FibroGen and AstraZeneca complete a phase II/III trial for Anaemia in China (PO) (NCT03303066) Updated 08 May 2023
30 Sep 2022 Trial Update Astellas Pharma discontinues further development in Chemotherapy-induced anaemia in company's assigned territories [1] Updated 07 Dec 2022
26 Aug 2022 Trial Update FibroGen completes enrolment in its phase III MATTERHORN trial for Anaemia in Australia, Belgium, Germany, Israel, Italy, Korea, Republic of, Russian Federation, Spain, United Kingdom, United States (NCT03263091) [124] Updated 30 Aug 2022
08 Aug 2022 Phase Change - Registered Registered for Anaemia in Mexico (PO) before August 2022 [18] Updated 11 Aug 2022
08 Aug 2022 Phase Change - Registered Registered for Anaemia in South Africa (PO) before August 2022 [18] Updated 11 Aug 2022
07 Aug 2022 Phase Change - Preregistration Preregistration for Anaemia in South Africa (PO) before August 2022 [18] Updated 11 Aug 2022
05 Jul 2022 Trial Update FibroGen and AstraZeneca withdrawn its phase III trial in Anaemia (In children, In adolescents) in USA before enrolment due to sponsors decision (PO) (NCT04621331) Updated 13 Jul 2022
03 Jun 2022 Scientific Update Efficacy and adverse events data of a phase II WHITNEY trial in Chemotherapy-induced anaemia presented at the 58th Annual Meeting of the American Society of Clinical Oncology (ASCO-2022) [137] Updated 05 Jul 2022
10 May 2022 Phase Change - Registered Registered for Anaemia in Russia (PO) [9] Updated 12 May 2022
31 Mar 2022 Trial Update FibroGen plans a phase III trial for Chemotherapy Induced Anemia in (In Adults , In the elderly) China (SC)(NCT05301517) Updated 31 Mar 2022
30 Mar 2022 Regulatory Status Roxadustat included on the renewed 2021 National Reimbursement Drug List (“NRDL”), released by China’s National Healthcare Security Administration with a meaningful price reduction [37] Updated 04 Apr 2022
16 Mar 2022 Phase Change - III Phase-III clinical trials in Chemotherapy-induced anaemia in China (PO) (NCT05301517) Updated 15 Jun 2022
11 Jan 2022 Biomarker Update Biomarkers information updated Updated 13 Jan 2022
11 Dec 2021 Scientific Update Pooled efficacy data from various phase III trials in Anaemia presented at the Annual Meeting and Exposition of the American Society of Hematology (ASH-HEM-2021) [94] Updated 29 Jan 2022
09 Nov 2021 Phase Change - Marketed Launched for Anaemia in Austria (PO) before November 2021 [13] Updated 17 Nov 2021
09 Nov 2021 Phase Change - Marketed Launched for Anaemia in Germany (PO) before November 2021 [13] Updated 17 Nov 2021
09 Nov 2021 Phase Change - Marketed Launched for Anaemia in Netherlands (PO) before November 2021 [13] Updated 17 Nov 2021
09 Nov 2021 Phase Change - Marketed Launched for Anaemia in United Kingdom (PO) before November 2021 [13] Updated 17 Nov 2021
11 Oct 2021 Trial Update Fibrogen in collaboration with AstraZeneca completes a phase IIIb trial for Anaemia in USA (PO) (NCT04410198) Updated 17 Feb 2022
19 Aug 2021 Phase Change - Registered Registered for Anaemia in European Union, Iceland, Liechtenstein and Norway (PO) [14] Updated 25 Aug 2021
19 Aug 2021 Regulatory Status Astellas Pharma plans to launch roxadustat in Anaemia in European Union, Iceland, Norway and Liechtenstein [14] Updated 25 Aug 2021
11 Aug 2021 Regulatory Status FibriGen receives complete response letter from the US FDA for roxadustat in Anaemia [22] Updated 16 Aug 2021
15 Jul 2021 Phase Change - Registered Registered for Anaemia in South Korea (PO) before July 2021 [19] Updated 19 Jul 2021
15 Jul 2021 Regulatory Status The US FDA Cardiovascular and Renal Drugs Advisory Committee (CRDAC) recommends not approving roxadustat for Anaemia due to chronic kidney disease (CKD) in adults [19] Updated 19 Jul 2021
09 Jul 2021 Trial Update FibroGen and AstraZeneca completes a phase IIIb trial in Anaemia (in patients with end stage renal disease on dialysis) (PO) (NCT04484857) Updated 30 Dec 2021
25 Jun 2021 Regulatory Status The Committee for Medicinal Products for Human Use (CHMP) recommends approval of roxadustat for Anaemia in European Union [16] Updated 29 Jun 2021
10 May 2021 Licensing Status FibroGen and Astellas agree to co-develop and commercialise roxadustat in USA, China, Australia, New Zealand, and South-East Asia, Japan, Europe, Turkey, Russia, the Middle East, and South Africa for Anaemia [3] Updated 17 May 2021
10 May 2021 Regulatory Status The Cardiovascular and Renal Drugs Advisory Committee (CRDAC) of the US FDA to hold Advisory Committee Meeting on roxadustat NDA in July 2021 [3] Updated 16 May 2021
23 Apr 2021 Trial Update FibroGen, AstraZeneca and Astellas Pharma completes the phase II WHITNEY trial in Chemotherapy-induced anaemia in USA (PO) (NCT04076943) Updated 10 Aug 2021
01 Mar 2021 Regulatory Status FibroGen expects decision of the European Medicines Agency (EMA) for review of the MAA of roxadustat in Anaemia, by mid-2021 [157] Updated 25 Aug 2021
01 Mar 2021 Scientific Update Efficacy and adverse events data from the phase III OLYMPUS trial in Anaemia published in Journal of the American Society of Nephrology in March 2021 [3] Updated 17 May 2021
01 Mar 2021 Phase Change - Registered Registered for Anaemia in Chile (PO) before March 2021 [21] Updated 05 Mar 2021
01 Mar 2021 Regulatory Status The Cardiovascular and Renal Drugs Advisory Committee of the US FDA plans to conduct an advisory committee meeting to review the new drug application (NDA) for roxadustat in USA [157] Updated 03 Mar 2021
25 Feb 2021 Scientific Update Efficacy and adverse events data from the phase III ALPS trial in Anaemia published in Nephrology Dialysis Transplantation [3] Updated 17 May 2021
31 Dec 2020 Patent Information FibroGen has patents pending for for roxadustat, its composition of matter, pharmaceutical compositions containing roxadustat in Canada and Japan [152] Updated 17 Jun 2021
23 Dec 2020 Scientific Update Pooled efficacy data from the three phase III HIMALAYAS, SIERRAS and ROCKIES trials in Anaemia released in Kidney International Reports [3] Updated 17 May 2021
18 Dec 2020 Regulatory Status FDA assigns PDUFA action date of 20/03/2021 for roxadustat for Anaemia in USA (PO) [24] Updated 05 Mar 2021
18 Dec 2020 Regulatory Status US FDA extends review period of NDA for roxadustat for Anaemia [24] Updated 22 Dec 2020
05 Dec 2020 Scientific Update Efficacy data from the phase III ANDES trial in Anaemia published in Kidney International Reports [3] Updated 17 May 2021
05 Dec 2020 Scientific Update Pooled efficacy data from three phase III OLYMPUS, ANDES, ALPS trials in Anaemia presented at the 62nd Annual Meeting and Exposition of the American Society of Hematology (ASH-Hem-2020) [56] Updated 31 Dec 2020
05 Dec 2020 Scientific Update Pooled efficacy data from six phase III trials in Anaemia presented at the 62nd Annual Meeting and Exposition of the American Society of Hematology (ASH-Hem-2020) [158] Updated 28 Dec 2020
05 Dec 2020 Scientific Update Pooled efficacy data from the three phase III HIMALAYAS, SIERRAS and ROCKIES trials in Anaemia presented at the 62nd Annual Meeting and Exposition of the American Society of Hematology (ASH-Hem-2020) [159] Updated 28 Dec 2020
05 Dec 2020 Scientific Update Pooled efficacy data from the phase III OLYMPUS, ANDES, ALPS trials in Anaemia presented at 62nd Annual Meeting and Exposition of the American Society of Hematology (ASH-2020) [91] [93] [92] Updated 28 Dec 2020
26 Nov 2020 Regulatory Status MHLW approves roxadustat for the treatment of Anemia in chronic kidney disease (in adult patients not on dialysis) in Japan [54] Updated 30 Nov 2020
20 Nov 2020 Regulatory Status AstraZeneca expects regulatory decision for Anaemia in the US in Q4 2020 [4] Updated 20 Nov 2020
01 Nov 2020 Phase Change - Preregistration Preregistration for Anaemia in Colombia (PO), prior to November 2020 [4] Updated 20 Nov 2020
01 Nov 2020 Phase Change - Preregistration Preregistration for Anaemia in Thailand (PO), prior to November 2020 [4] Updated 20 Nov 2020
01 Nov 2020 Phase Change - III Phase-III clinical trials in Anaemia (In children, In adolescents) in USA (PO) (NCT04621331) Updated 12 Nov 2020
22 Oct 2020 Scientific Update Pooled adverse events data from a phase III trial in Anemia released by FibroGen [39] Updated 26 Oct 2020
30 Jul 2020 Phase Change - Preregistration Preregistration for Anaemia in Chile, Brazil, Australia, South Korea, India (PO), before July 2020 [20] Updated 15 Sep 2020
24 Jul 2020 Trial Update FibroGen and AstraZeneca plans a phase IIIb trial in Anaemia (in patients with end stage renal disease on dialysis) (PO) (NCT04484857) Updated 29 Jul 2020
17 Jul 2020 Trial Update FibroGen and AstraZeneca initiates a phase IIIb trial in Anaemia (in patients with end stage renal disease on dialysis) (PO) (NCT04484857) Updated 06 Aug 2020
01 Jul 2020 Licensing Status FibroGen and AstraZeneca entered into an amendment to revise the existing licence agreement for roxadustat in China [4] Updated 20 Nov 2020
12 Jun 2020 Scientific Update Efficacy data from the phase III DOLOMITES trial in Anaemia (in chronic kidney disease patients not on dialysis) presented at the European Renal Association – European Dialysis and Transplant Association (ERA-EDTA) [98] Updated 17 Jun 2020
08 Jun 2020 Scientific Update Efficacy and adverse events data from the phase III DOLOMITES trial in Anaemia (in chronic kidney disease patients not on dialysis) presented at the 57th European Renal Association – European Dialysis and Transplant Association (ERA-EDTA) [69] Updated 10 Jun 2020
01 Jun 2020 Trial Update Fibrogen in collaboration with AstraZeneca plans a phase IIIb trial for Anaemia (NCT04410198) Updated 04 Jun 2020
27 May 2020 Trial Update Fibrogen in collaboration with AstraZeneca initiates a phase IIIb trial for Anaemia in USA (PO) (NCT04410198) Updated 08 Jul 2020
20 May 2020 Phase Change - Preregistration Preregistration for Anaemia in European Union (PO) [15] Updated 22 May 2020
20 May 2020 Regulatory Status The European Medicines Agency accepts MAA for roxadustat for Anaemia for review [15] Updated 22 May 2020
07 May 2020 Regulatory Status FibroGen announces intention to submit Marketing Authorization Application for Anaemia in Europe in second quarter of 2020 [160] Updated 05 Mar 2021
20 Apr 2020 Patent Information United Kingdom's High Court of Justice holds certain patents related to methods of using hypoxia-inducible factor prlyl hydroxylase inhibitors to be invalid [154] Updated 04 May 2020
31 Mar 2020 Regulatory Status Health Canada accepts NDS for roxadustat for Anaemia for review (Health Canada website, September 2020) Updated 15 Sep 2020
26 Mar 2020 Trial Update Astellas Pharma and FibroGen completes a phase III trial for Anaemia (in non-dialysis chronic kidney disease patients) in Japan (PO) (NCT02988973) Updated 20 Apr 2020
11 Feb 2020 Regulatory Status USA FDA accepts NDA for roxadustat for Anaemia for review in USA [25] Updated 14 Feb 2020
30 Jan 2020 Regulatory Status Astellas Pharma and FibroGen files sNDA for treatment of Anaemia associated with chronic kidney disease (CKD) in non-dialysis dependent (NDD) patients in Japan [55] Updated 31 Jan 2020
31 Dec 2019 Phase Change - Preregistration Preregistration for Anaemia in Canada (PO), Taiwan (PO), Mexico (PO), Philippines (PO), Singapore (PO), before December 2019 [36] Updated 15 Sep 2020
31 Dec 2019 Trial Update FibroGen completes a phase II/III trial in Anaemia in USA and Puerto Rico (NCT01630889) Updated 08 Jul 2020
23 Dec 2019 Phase Change - Preregistration Preregistration for Anaemia in USA (PO) [26] Updated 27 Dec 2019
07 Dec 2019 Scientific Update Efficacy and adverse events data from a phase III trial for Anaemia (in patients with lower Risk myelodysplastic syndrome with low red blood cell transfusion burden) presented at the 61st Annual Meeting and Exposition of the American Society of Hematology (ASH-2019) [123] Updated 18 Dec 2019
04 Dec 2019 Regulatory Status AstraZeneca announces intention to submit regulatory application for anaemia of myelodysplastic syndrome in 2021 [161] Updated 17 Aug 2020
11 Nov 2019 Regulatory Status Astellas Pharma announces intention to submit MAA to the EMA for dialysis and non dialysis dependent CKD Anaemia in the first half of 2020 [17] Updated 22 May 2020
11 Nov 2019 Phase Change - Marketed Launched for Anaemia in China (PO) [17] Updated 21 Nov 2019
11 Nov 2019 Regulatory Status FibroGen plans to submit regulatory filings to the authorities other than the US FDA and EMA [17] Updated 21 Nov 2019
08 Nov 2019 Scientific Update Efficacy and adverse events data from the phase III OLYMPUS and ROCKIES trials in Anaemia released by AstraZeneca [48] Updated 20 Nov 2019
08 Nov 2019 Scientific Update Pooled analysis efficacy and safety data from phase III trials in Anaemia (associated with chronic kidney disease) released by FibroGen [52] [51] Updated 15 Nov 2019
08 Nov 2019 Scientific Update Updated pooled efficacy and cardiovascular adverse events data from phase III trials in Anaemia released by FibroGen [162] Updated 12 Nov 2019
07 Nov 2019 Scientific Update Efficacy data from the phase III HIMALAYAS trial in Anaemia (associated with chronic kidney disease) released by FibroGen [110] Updated 15 Nov 2019
06 Nov 2019 Trial Update Astellas completes the phase III Dolomites trial in Anaemia (in chronic kidney disease patients not on dialysis) in Ukraine, Austria, Belarus, Bulgaria, Croatia, Czech Republic, Denmark, France, Finland, Germany, Georgia, Hungary, Ireland, Israel, Latvia, Netherlands, Macedonia, Portugal, Montenegro, Poland, Romania, Russia, Slovakia, Serbia, Sweden, Slovenia, Spain and United Kingdom (PO) (NCT02021318) Updated 17 Dec 2019
01 Nov 2019 Phase Change - Marketed Launched for Anaemia in Japan (PO) [55] Updated 31 Jan 2020
14 Oct 2019 Trial Update Astellas in collaboration with FibroGen completes a phase I trial in healthy volunteers in Germany (PO) (NCT03960489) (EudraCT2018-002924-18) Updated 26 Nov 2019
11 Oct 2019 Regulatory Status FibroGen announces intention to submit NDA to US FDA for Anaemia by Q4 of 2019 [96] Updated 27 Dec 2019
20 Sep 2019 Phase Change - Registered Registered for Anaemia in Japan (PO) [32] Updated 23 Sep 2019
22 Aug 2019 Regulatory Status National Medical Products Administration approves roxadustat for treatment of Anaemia in non-dialysis-dependent chronic kidney disease patients in China [27] Updated 23 Aug 2019
08 Aug 2019 Regulatory Status FibroGen expect approval of roxadustat for Anaemia in non-dialysis-dependent chronic kidney diseases in China in the third quarter of 2019 [163] Updated 05 Mar 2020
08 Aug 2019 Regulatory Status FibroGen expect approval of roxadustat for Anaemia in dialysis-dependent chronic kidney diseases in Japan in the second half of 2019 [163] Updated 23 Sep 2019
06 Aug 2019 Phase Change - II Phase-II clinical trials in Chemotherapy-induced anaemia in USA (PO) (NCT04076943) Updated 10 Sep 2019
24 Jul 2019 Scientific Update Updated efficacy and adverse events data from the phase III FGCL-4592-808 trial in Anaemia released by FibroGen [63] Updated 29 Jul 2019
11 Jul 2019 Trial Update Astellas in collaboration with FibroGen initiates enrolment in a phase I trial in healthy volunteers in Germany (EudraCT2018-002924-18) Updated 05 Aug 2019
11 Jun 2019 Trial Update FibroGen initiates a phase IV trial for Anaemia (in chronic kidney disease patients on dialysis) in China (PO) (NCT04059913) Updated 21 Aug 2019
28 May 2019 Trial Update Astellas Pharma plans a phase I trial for Healthy volunteers (PO) (NCT03960489) Updated 22 Jul 2019
10 May 2019 Scientific Update Pooled cardiovascular safety data from phase III trials in Anaemia released by AstraZeneca [164] Updated 16 May 2019
09 May 2019 Regulatory Status FibroGen submits a marketing authorisation application to the National Medical Products Administration (NMPA) seeking regulatory approval in Anaemia (for non-dialysis dependent (NDD) chronic kidney disease (CKD) patients) in China before May 2019 [28] Updated 29 Jul 2019
09 May 2019 Scientific Update Pooled efficacy and cardiovascular adverse events data from phase III trials in Anaemia released by FibroGen [165] Updated 16 May 2019
20 Dec 2018 Scientific Update Efficacy data from three phase III trials (ANDES, HIMALAYAS, SIERRAS) in Anaemia (associated with chronic kidney disease) released by FibroGen [72] Updated 28 Dec 2018
17 Dec 2018 Regulatory Status AstraZeneca and FibroGen expect to launch roxadustat in China in the second half of 2019 [29] Updated 21 Nov 2019
17 Dec 2018 Phase Change - Registered Registered for Anaemia in dialysis-dependent (DD) chronic kidney disease (CKD) patients in China (PO) - First global approval [29] Updated 19 Dec 2018
06 Dec 2018 Phase Change - II/III FibroGen initiates enrolment in a phase II/III trial for Anaemia (in patients with lower risk myelodysplastic syndrome) in China (PO) (NCT03303066) [127] Updated 12 Dec 2018
06 Dec 2018 Regulatory Status FibroGen announces intention to launch to roxadustat for Anaemia [127] Updated 12 Dec 2018
31 Oct 2018 Scientific Update Updated efficacy and safety data from two phase III trials (1517-CL-0302 and 1517-CL-0307) in Anaemia presented at the American Society of Nephrology Kidney Week 2018 annual meeting (ASN-2018) [99] Updated 05 Nov 2018
25 Oct 2018 Scientific Update Updated efficacy data from two phase III trials (FGCL-4592-808 and FGCL-4592-806) in Anaemia presented at the American Society of Nephrology Kidney Week 2018 annual meeting (ASN-2018) [64] Updated 01 Nov 2018
04 Oct 2018 Trial Update AstraZeneca completes a phase III trial in Anaemia (in patients with chronic kidney disease not on dialysis) in Argentina, Brazil, Bulgaria, Canada, Colombia, Czech Republic, Germany, Hungary, India, Malaysia, Mexico, Multinational, Peru, Philippines, Poland, Puerto Rico, Romania, Russia, Slovakia, South Korea, Spain, Taiwan, Thailand, Turkey, Ukraine, USA, Vietnam (NCT02174627) Updated 04 Dec 2018
01 Oct 2018 Phase Change - Preregistration Preregistration for Anaemia (associated with chronic kidney disease in patients on dialysis) in Japan (PO) [34] Updated 05 Oct 2018
26 Sep 2018 Trial Update AstraZeneca completes a phase III trial in Anaemia (in chronic kidney disease patients on dialysis) in Argentina, Australia, Brazil, Bulgaria, Canada, Czech Republic, Hungary, India, Mexico, Peru, Philippines, Poland, Romania, Russia, Slovakia, Spain, Sweden, Thailand, Ukraine, USA, Vietnam (NCT02174731) Updated 04 Dec 2018
21 Sep 2018 Trial Update FibroGen completes the phase III Himalayas trial in Anaemia (in haemodialysed patients with end stage renal disease) in USA, Belarus, Argentina, Chile, Colombia, Malaysia, Mexico, Poland, Romania, Taiwan, Thailand and Ukraine (PO) (NCT02052310) Updated 12 Apr 2019
20 Sep 2018 Trial Update FibroGen completes the phase III ANDES trial in Anaemia (in chronic kidney disease patients not on dialysis) in USA, Argentina, Chile, Colombia, Hong Kong, South Korea, Malaysia, Mexico, New Zealand, Peru, Philippines, Puerto Rico, Singapore, Taiwan and Thailand (PO) (NCT01750190) Updated 12 Apr 2019
19 Sep 2018 Trial Update FibroGen completes the phase III SIERRAS trial in Anaemia (associated with dialysis-dependent CKD) in USA and Puerto Rico (PO) (NCT02273726) Updated 12 Apr 2019
15 Aug 2018 Trial Update Astellas Pharma and FibroGen completes a phase III trial for Anaemia (in non-dialysis chronic kidney disease patients) in Japan (PO) (NCT02964936) Updated 10 Sep 2018
06 Jul 2018 Trial Update Astellas Pharma and Fibrogen completes a phase III PYRENEES trial for Anaemia (for maintenance treatment in CKD patients on dialysis) in United Kingdom, Belgium, Bulgaria, Croatia, Czech Republic, France, Georgia, Germany, Hungary, Italy, Poland, Portugal, Romania, Russia, Spain, Slovakia and Serbia (PO) (NCT02278341) (EudraCT2013-001497-16) Updated 23 Aug 2018
07 Jun 2018 Trial Update FibroGen completes enrolment in its phase III trial for Anaemia (associated with dialysis-dependent CKD) in the US [59] (NCT02052310) Updated 08 Jun 2018
07 Jun 2018 Trial Update FibroGen completes enrolment in its phase III trial for Anaemia (associated with dialysis-dependent CKD) in the US [59] (NCT02174731) Updated 08 Jun 2018
07 Jun 2018 Trial Update FibroGen completes enrolment in its phase III trial for Anaemia (associated with dialysis-dependent CKD) in the US [59] (NCT02273726) Updated 08 Jun 2018
07 Jun 2018 Trial Update FibroGen completes enrolment in its phase III trial for Anaemia (associated with non-dialysis-dependent CKD) in the US, Canada, Brazil, Mexico, Peru, Puerto Rico, Argentina, Colombia, India, Bulgaria, Czech Republic, Germany, Hungary, Romania, Poland, Slovakia, Spain, Russia, Ukraine, Turkey, South Korea, Philippines, Taiwan, Malaysia, Thailand and Vietnam [59] (NCT02174627) Updated 08 Jun 2018
31 May 2018 Scientific Update Topline safety and efficacy data from phase III trial in Anaemia (haemodialysis dependent chronic kidney disease patients) released by Astellas Pharma [100] Updated 06 Jun 2018
29 May 2018 Phase Change - II Phase-II clinical trials in Anaemia (in patients with Myelodysplastic syndromes) in China (PO) (NCT03303066) (FibroGen pipeline, May 2018) Updated 29 May 2018
09 May 2018 Regulatory Status Astellas announces intention to submit NDA for Anaemia (associated with dialysis-dependent CKD) in Japan in 2018 [47] Updated 05 Oct 2018
27 Mar 2018 Phase Change - I Phase-I clinical trials in Anaemia (in patients with Myelodysplastic syndromes) in China (PO) (FibroGen pipeline, March 2018) Updated 27 Mar 2018
15 Mar 2018 Trial Update Astellas Pharma and FibroGen completes a phase III trial for Anaemia (in haemodialysis dependent chronic kidney disease patients) in Japan (PO) (NCT02952092) Updated 13 Apr 2018
27 Feb 2018 Patent Information FibroGen has patent protection for roxadustat in USA and China [153] Updated 26 Mar 2018
27 Feb 2018 Regulatory Status FibroGen announces intention to submit applications for marketing approvals for Anaemia in the European Union Updated 05 Mar 2018
12 Dec 2017 Trial Update Astellas Pharma and FibroGen complete a phase III trial for Anaemia (In erythropoiesis stimulating agent-naive, chronic kidney disease patients undergoing haemodialysis) in Japan (PO) (NCT02780141) Updated 04 Jan 2018
11 Dec 2017 Trial Update Astellas Pharma and FibroGen completes a phase I pharmacokinetics trial in United Kingdom and Germany(NCT02965040) Updated 05 Feb 2018
07 Dec 2017 Trial Update FibroGen initiates enrolment in a phase III trial for Anaemia (in patients with lower Risk myelodysplastic syndrome with low red blood cell transfusion burden) in Israel, Italy, South Korea, Russia and UK after September 2017 (PO) (NCT03263091) Updated 04 Apr 2022
28 Nov 2017 Trial Update Astellas Pharma completes a phase III trial for Anaemia (In erythropoiesis stimulating agent-experienced chronic kidney disease patients undergoing haemodialysis) in Japan (PO) (NCT02779764) Updated 26 Dec 2017
01 Nov 2017 Trial Update Astellas completes a phase III trial in Anaemia (in chronic kidney disease patients not on dialysis) in United Kingdom, Belgium, Bulgaria, Italy, Poland, Romania, Russia, Spain, South Africa, Hungary, Greece, Belarus, Colombia, Dominican Republic, Estonia, Georgia, Guatemala, Panama, Peru, Serbia, Turkey and Ukraine (PO) (NCT01887600) Updated 06 Dec 2017
31 Oct 2017 Scientific Update Top-line efficacy data from a phase III trial in Anaemia (In chronic kidney disease patients undergoing peritoneal dialysis) released by Astellas and FibroGen [106] Updated 24 Nov 2017
30 Oct 2017 Regulatory Status Roxadustat receives priority review status for Anaemia in China [30] Updated 12 Feb 2018
18 Oct 2017 Phase Change - Preregistration Preregistration for Anaemia in dialysis-dependent CKD patients in China (PO) [31] Updated 23 Oct 2017
17 Oct 2017 Regulatory Status China Food and Drug Administration (CFDA) accepts NDA for Roxadustat for anaemia in non-dialysis-dependent CKD (NDD-CKD) patients for review [31] Updated 19 Dec 2018
07 Sep 2017 Phase Change - III Phase-III clinical trials in Anaemia in Italy, Belgium, Spain, Poland, France, Denmark (PO) (NCT03263091) (EudraCT Number 2017-001773-17) Updated 25 Aug 2023
07 Sep 2017 Trial Update FibroGen initiates enrolment in its phase III MATTERHORN trial for Anaemia in Denmark, Canada, France, India and Poland (NCT03263091) Updated 25 Aug 2023
07 Sep 2017 Trial Update FibroGen initiates enrolment in a phase III trial for Anaemia (in patients with lower Risk myelodysplastic syndrome with low red blood cell transfusion burden) in Australia, after September 2017 (PO) (NCT03263091) Updated 19 Dec 2018
07 Sep 2017 Trial Update FibroGen initiates enrolment in a phase III trial for Anaemia (in patients with lower Risk myelodysplastic syndrome with low red blood cell transfusion burden) in Spain, Germany, Belgium and USA (PO) (NCT03263091) (EudraCT2017-001773-17) Updated 04 Oct 2017
02 Aug 2017 Trial Update Astellas Pharma completes a phase III trial for Anaemia (In chronic kidney disease patients undergoing peritoneal dialysis) in Japan (PO) (NCT02780726) Updated 22 Aug 2017
14 Jun 2017 Trial Update FibroGen completes a phase III trial in Anaemia (in chronic kidney disease patients on dialysis) in China (NCT02652806) Updated 04 Sep 2017
13 Jun 2017 Trial Update FibroGen completes a phase III trial in Anaemia in China (NCT02652819) Updated 04 Sep 2017
05 Jun 2017 Patent Information European Patent Office gave a decision against FibroGen for an opposition filed by Akebia Therapeutics, Bayer Group, and Glaxo Group for the European patent number 2 322 155, related to the therapeutic use of certain small molecule inhibitors of hypoxia-inducible factor (HIF) prolyl hydroxylase, in Europe [155] Updated 16 Jun 2017
05 Jun 2017 Patent Information Fibrogen has patent protection for the use of hypoxia-inducible factor alpha stabilisers for enhancing erythropoiesis in Europe [155] Updated 16 Jun 2017
31 Mar 2017 Trial Update FibroGen plans a phase II/III trial for Anaemia (associated with Myelodysplastic syndrome) in China (PO) (NCT03303066) in first quarter of 2018 [129] Updated 29 May 2018
31 Mar 2017 Trial Update FibroGen plans a pivotal phase III trial for Anaemia (associated with Myelodysplastic syndrome) in USA in third quarter of 2017 [129] Updated 14 Nov 2017
31 Mar 2017 Regulatory Status China Food and Drug Administration (CFDA) approves Clinical Trial Application for roxadustat in Anaemia (associated with myelodysplastic syndrome) [129] Updated 05 Apr 2017
30 Mar 2017 Scientific Update Efficacy data from phase II trial in Anaemia released by FibroGen [89] Updated 19 Apr 2017
30 Jan 2017 Regulatory Status AstraZeneca announces intention to submit NDA to China FDA in 2017 [8] Updated 02 Feb 2017
30 Jan 2017 Regulatory Status Clinical Trial Application (CTA) for roxadustat is under review by China FDA [8] Updated 02 Feb 2017
30 Jan 2017 Scientific Update Positive topline efficacy data from two phase III trials in Anaemia released by FibroGen [8] Updated 02 Feb 2017
01 Jan 2017 Trial Update Astellas Pharma and FibroGen initiates a phase III trial for Anaemia (in non-dialysis chronic kidney disease patients) in Japan (PO) (NCT02988973) Updated 07 Feb 2017
01 Jan 2017 Trial Update Astellas Pharma and FibroGen initiate a phase III trial for Anaemia (in non-dialysis chronic kidney disease patients) in Japan (PO) (NCT02964936) (Astellas Pharma pipeline, January 2017) Updated 02 Feb 2017
31 Dec 2016 Regulatory Status The US FDA approves an IND application for a phase III trial in Anaemia (in myelodysplastic syndrome patients) prior to December 2016 [121] Updated 06 Mar 2017
12 Dec 2016 Trial Update Astellas Pharma and FibroGen initiates enrolment in a phase I pharmacokinetics trial in Germany NCT02965040) Updated 19 Dec 2018
12 Dec 2016 Trial Update Astellas Pharma and FibroGen initiates enrolment in a phase I pharmacokinetics trial in United Kingdom (NCT02965040) Updated 05 Feb 2018
08 Dec 2016 Trial Update Astellas Pharma and FibroGen plan a phase III trial for Anaemia (in non-dialysis chronic kidney disease patients) in Japan (PO) (NCT02988973) Updated 14 Dec 2016
01 Dec 2016 Trial Update Astellas Pharma and FibroGen initiate a phase I pharmacokinetics trial in Germany (NCT02965040) Updated 28 Feb 2017
01 Dec 2016 Trial Update Astellas Pharma and FibroGen completes a phase I pharmacokinetics trial in Healthy volunteers in Japan (PO) (NCT02952040) Updated 10 Feb 2017
13 Nov 2016 Trial Update Astellas Pharma and FibroGen plan a phase III trial for Anaemia (in non-dialysis chronic kidney disease patients) in Japan (PO) (NCT02964936) Updated 22 Nov 2016
11 Nov 2016 Trial Update Astellas Pharma and FibroGen plan a phase I pharmacokinetics trial in United Kingdom and Germany (PO) (NCT02965040) Updated 22 Nov 2016
08 Nov 2016 Regulatory Status FibroGen files an IND application with the US FDA in USA for Anaemia (in myelodysplastic syndrome patients) [68] Updated 14 Nov 2016
08 Nov 2016 Trial Update FibroGen plans a phase III trial in Anaemia (in myelodysplastic syndrome patients) in USA [68] Updated 14 Nov 2016
01 Nov 2016 Trial Update Astellas Pharma and FibroGen initiates a phase III trial for Anaemia (in haemodialysis dependent chronic kidney disease patients) in Japan (PO) (NCT02952092) Updated 07 Feb 2017
01 Nov 2016 Trial Update Astellas Pharma and FibroGen initiate a phase I pharmacokinetics trial in Healthy volunteers in Japan (PO) (NCT02952040) Updated 14 Dec 2016
31 Oct 2016 Trial Update Astellas Pharma and FibroGen plan a phase I pharmacokinetics trial in Healthy volunteers in Japan (PO) (NCT02952040) Updated 08 Nov 2016
31 Oct 2016 Trial Update Astellas Pharma and FibroGen plan a phase III trial for Anaemia (in haemodialysis chronic kidney disease patients) in Japan (PO) (NCT02952092) Updated 08 Nov 2016
31 Oct 2016 Trial Update FibroGen completes enrolment in a phase III trial in Anaemia in China (NCT02652819) [65] Updated 04 Nov 2016
08 Aug 2016 Trial Update FibroGen completes enrolment in a phase III trial in Anaemia (in chronic kidney disease patients on dialysis) in China (NCT02652806) [45] Updated 10 Aug 2016
01 Aug 2016 Trial Update Astellas Pharma and FibroGen complete a phase I pharmacokinetics trial in Healthy volunteers in Japan (PO) (NCT02805374) Updated 06 Sep 2016
25 Jul 2016 Scientific Update Safety and efficacy data from phase II trials in Anaemia released by Astellas and FibroGen [73] Updated 16 Aug 2016
01 Jul 2016 Trial Update Astellas Pharma and FibroGen initiate a phase I pharmacokinetics trial in Healthy volunteers in Japan (PO) (NCT02805374) Updated 06 Sep 2016
16 Jun 2016 Trial Update Astellas Pharma and FibroGen plan a phase I pharmacokinetics trial in Healthy volunteers in Japan (PO) (NCT02805374) Updated 22 Jun 2016
09 Jun 2016 Phase Change - III Phase-III clinical trials in Anaemia (in chronic kidney disease patients indergoing peritoneal dialysis) in Japan (PO) [104] (NCT02780726) Updated 14 Jun 2016
20 May 2016 Trial Update In collaboration with FibroGen, Astellas Pharma plans a phase III trial for Anaemia (In chronic kidney disease patients undergoing peritoneal dialysis) in Japan (PO) (NCT02780726) Updated 26 May 2016
16 May 2016 Phase Change - III Phase-III clinical trials in Anaemia (In erythropoiesis stimulating agent-experienced chronic kidney disease patients undergoing haemodialysis) in Japan (PO) (NCT02779764) Updated 19 Dec 2018
01 May 2016 Trial Update Astellas Pharma in collaboration with FibroGen initiates a phase III trial for Anaemia (In erythropoiesis stimulating agent-naive, chronic kidney disease patients undergoing haemodialysis) in Japan (PO) (NCT02780141) Updated 21 Jun 2016
30 Apr 2016 Trial Update Astellas Pharma completes a pharmacokinetic phase I trial in Healthy volunteers in Japan (NCT02693613) Updated 11 May 2016
20 Apr 2016 Scientific Update Positive efficacy, adverse events and pharmacodynamics data from a phase IIb trial in Anaemia (in Chronic kidney disease patients not on dialysis) released by Fibrogen [77] Updated 28 Apr 2016
02 Mar 2016 Trial Update Astellas Pharma plans a pharmacokinetic phase I trial in Healthy volunteers in Japan (NCT02693613) Updated 02 Mar 2016
16 Feb 2016 Scientific Update Adverse events and efficacy data from a phase II trial in Anaemia released by FibroGen [118] Updated 18 Feb 2016
01 Feb 2016 Trial Update Astellas Pharma initiates enrolment in a pharmacokinetic phase I trial in Healthy volunteers in Japan (NCT02693613) Updated 31 Mar 2016
20 Jan 2016 Trial Update Astellas Pharma and Fibrogen initiates enrolment in a phase III trial for Anaemia (for maintenance treatment in CKD patients on dialysis) in Russia, Czech Republic, Georgia and Slovakia (PO) after November 2014 (NCT02278341) Updated 20 Jan 2016
01 Dec 2015 Trial Update FibroGen initiates a phase III trial for Anaemia (in patients with chronic kidney disease not on dialysis) in China (NCT02652819) Updated 08 Feb 2016
01 Dec 2015 Phase Change - III Phase-III clinical trials in Anaemia (in chronic kidney disease patients on dialysis) in China (PO) (NCT02652806) Updated 27 Jan 2016
01 Dec 2015 Trial Update Astellas completes a phase II trial in Anaemia (in non-dialysis dependent CKD patients) in Japan (PO) (NCT01964196) Updated 20 Jan 2016
22 Oct 2015 Scientific Update Efficacy data from a phase II trial in Anaemia released by FibroGen [113] Updated 29 Oct 2015
24 Sep 2015 Phase Change - III Phase-III clinical trials in Anaemia in Argentina, Chile, Colombia, Mexico and Peru (PO) Updated 05 Oct 2015
18 Sep 2015 Phase Change - III Phase-III clinical trials in Anaemia in Sweden, Brazil, Puerto Rico and Turkey (PO) Updated 05 Oct 2015
02 Sep 2015 Scientific Update Efficacy and adverse events data from phase IIa trial in Anemia (in patients with chronic kidney disease not on dialysis) released by FibroGen [84] Updated 02 Sep 2015
20 May 2015 Active Status Review Roxadustat is still in phase-III development for Anaemia in USA and Europe and phase-II development in China, Puerto Rico and Japan Updated 10 Sep 2015
12 May 2015 Trial Update Fibrogen plans two phase III trials for Anaemia in China [46] Updated 18 Jun 2015
31 Dec 2014 Trial Update FibroGen initiates enrolment in a phase III trial in Anaemia (in patients with end stage renal disease on dialysis, maintenance therapy) in Puerto Rico, after December 2014(NCT02273726) Updated 19 Dec 2018
01 Dec 2014 Trial Update FibroGen initiates enrolment in a phase III trial in Anaemia (in patients with end stage renal disease on dialysis, maintenance therapy) in USA (NCT02273726) Updated 26 Feb 2015
01 Nov 2014 Trial Update Astellas Pharma and Fibrogen initiates enrolment in a phase III trial for Anaemia (in end stage renal disease patients on stable dialysis) in Romania after November 2014 (NCT02278341) Updated 14 Sep 2015
01 Nov 2014 Phase Change - III Phase-III clinical trials in Anaemia (for maintenance treatment in CKD patients on dialysis) in Serbia (PO) (NCT02278341) Updated 18 Jun 2015
01 Nov 2014 Trial Update Astellas Pharma and Fibrogen initiates enrolment in a phase III trial for Anaemia (in end stage renal disease patients on stable dialysis) in Bulgaria, Germany and Croatia (PO) after November 2014 (NCT02278341) Updated 18 Jun 2015
01 Nov 2014 Phase Change - III Phase-III clinical trials in Anaemia (for maintenance treatment in CKD patients on dialysis) in France (PO) (NCT02278341) Updated 26 Feb 2015
01 Nov 2014 Trial Update Astellas Pharma initiates enrolment in a phase III trial for Anaemia (in end stage renal disease patients on dialysis) in Belgium, Hungary, Italy, Poland, Portugal, Spain and United Kingdom (NCT02278341) Updated 26 Feb 2015
01 Nov 2014 Trial Update Astellas Pharma initiates enrolment in a phase III trial for Anaemia (in end stage renal disease patients on dialysis) in Spain (EudraCT2013-001497-16) Updated 17 Dec 2014
01 Nov 2014 Trial Update Astellas Pharma initiates enrolment in a phase III trial for Anaemia (in end stage renal disease patients on dialysis) in Hungary and Italy (NCT02278341) Updated 17 Dec 2014
28 Oct 2014 Trial Update Astellas Pharma and FibroGen plan a phase III trial in Anaemia (in patients with end stage renal disease on dialysis) in Europe (NCT02278341) Updated 10 Nov 2014
28 Oct 2014 Trial Update FibroGen plans a phase III trial in Anaemia (in patients with end stage renal disease on dialysis) in USA (NCT02273726) Updated 28 Oct 2014
01 Sep 2014 Trial Update Astellas Pharma completes a phase II trial in Anaemia (in dialysed patients with end-stage renal disease) in Japan (NCT01888445) Updated 11 Nov 2014
01 Jul 2014 Trial Update AstraZeneca initiates a phase III trial for Anaemia (in patients with chronic kidney disease on dialysis) in USA, Canada, Mexico, Peru, Australia, Bulgaria, the Czech Republic, Hungary, India, Mexico, Peru, Poland, Romania, Slovakia, Sweden, Spain, Russia, Ukraine, Philippines, Thailand and Vietnam (NCT02174731) Updated 22 Aug 2014
30 Jun 2014 Trial Update AstraZeneca initiates a phase III trial for Anaemia (in patients with chronic kidney disease not on dialysis) in USA (NCT02174627) Updated 21 Aug 2014
01 Jun 2014 Phase Change - III Phase-III clinical trials in Anaemia in India (PO) after June 2014 (NCT02174627) Updated 23 Feb 2016
01 Jun 2014 Phase Change - III Phase-III clinical trials in Anaemia in Vietnam, Ukraine, Hungary, Slovakia, Russia, Poland, Spain, Czech Republic, Canada and Bulgaria (PO) after June 2014 (NCT02174627) Updated 19 Jun 2015
01 Jun 2014 Trial Update AstraZeneca initiates a phase III trial for Anaemia (in patients with chronic kidney disease not on dialysis) in Germany, Argentina, Colombia, South Korea and Taiwan (PO) after June 2014 (NCT02174627) Updated 19 Jun 2015
15 Apr 2014 Phase Change - III Phase-III clinical trials in Anaemia (in dialysed patients with end-stage renal disease) in South Korea (PO) Updated 24 Apr 2014
15 Apr 2014 Phase Change - III Phase-III clinical trials in Anaemia (in non-haemodialysed patients with chronic kidney disease) in Slovakia (PO) Updated 24 Apr 2014
18 Mar 2014 Phase Change - III Phase-III clinical trials in Anaemia (in chronic kidney disease patients not on dialysis) in Panama, Guatemala, Georgia, Dominican Republic, Belarus, Greece (PO) (NCT01887600) after March 2014 Updated 06 Dec 2017
18 Mar 2014 Trial Update Astellas initiates enrolment in a phase III trial in Anaemia (in Chronic kidney disease patients not on dialysis) in Hungary, Colombia, Estonia, Peru, Serbia, Turkey and Ukraine (PO) (NCT01887600) after March 2014 Updated 06 Dec 2017
18 Mar 2014 Phase Change - III Phase-III clinical trials in Anaemia (in non-haemodialysed patients with chronic kidney disease) in South Africa (PO) Updated 24 Apr 2014
12 Mar 2014 Phase Change - III Phase-III clinical trials in Anaemia (in chronic kidney disease patients not on dialysis) in Montenegro and Macedonia (PO) (NCT02021318) Updated 26 Mar 2018
01 Feb 2014 Phase Change - III Phase-III clinical trials in Anaemia in Germany, Austria, Croatia, Ireland, Israel, Netherlands (PO) Updated 20 May 2015
31 Jan 2014 Phase Change - III Phase-III clinical trials in Anaemia in Australia & South Korea (PO) Updated 14 Feb 2014
15 Jan 2014 Phase Change - III Phase-III clinical trials in Anaemia (in dialysed patients with end-stage renal disease) in Latvia (PO) Updated 24 Apr 2014
14 Jan 2014 Trial Update Astellas Pharma plans a phase III trial for Anaemia (in non-haemodialysed patients with chronic kidney disease) in European Union and Israel (NCT02021318) Updated 14 Jan 2014
31 Dec 2013 Trial Update Astellas Pharma Europe & FibroGen complete a phase I trial in Healthy adult & elderly volunteers in Germany (NCT02161796) Updated 23 Jun 2014
31 Dec 2013 Trial Update Astellas Pharma & FibroGen complete a phase I trial in subjects with hepatic impairment in Bulgaria (NCT02161224) Updated 16 Jun 2014
31 Dec 2013 Phase Change - III Phase-III clinical trials in Anaemia (in haemodialysed patients with end-stage renal disease) in Estonia after December 2013 (PO) Updated 20 Feb 2014
04 Dec 2013 Phase Change - III Phase-III clinical trials in Anaemia (in non-haemodialysed patients with chronic kidney disease) in Slovenia, Portugal, Denmark, Finland & Czech Republic (PO) Updated 24 Apr 2014
01 Dec 2013 Trial Update Fibrogen, Astellas Pharma and AstraZeneca initiate enrolment in the Himalayas phase III trial for Anaemia (in haemodialysed patients with end stage renal disease) in USA, Belarus, Argentina, Chile, Colombia, Malaysia, Mexico, Poland, Romania, Taiwan, Thailand and Ukraine after December 2013 (NCT02052310) Updated 26 Mar 2018
30 Nov 2013 Trial Update Astellas initiates enrolment in a phase II trial for Anaemia (in non-haemodialysed patients with chronic kidney disease) in Japan Updated 15 Jan 2014
12 Nov 2013 Scientific Update Efficacy data from a phase II trial in Anaemia (in patients with chronic kidney disease on dialysis) released by FibroGen [166] Updated 30 Nov 2013
12 Nov 2013 Scientific Update Efficacy & adverse events data from a phase II trial in Anaemia (in non-dialysed Chinese patients with chronic kidney disease) presented at the American Society of Nephrology Kidney Week (ASN-2013) [87] Updated 29 Nov 2013
01 Nov 2013 Trial Update Astellas Pharma and FibroGen complete a phase I pharmacokinetics trial in healthy volunteers in Germany (NCT02252731) Updated 26 Mar 2018
30 Sep 2013 Phase Change - I Phase-I clinical trials in Anaemia (in healthy adult & elderly volunteers) in Germany (PO) Updated 23 Jun 2014
24 Sep 2013 Phase Change - III Phase-III clinical trials in Anaemia in Bulgaria (PO) Updated 08 Oct 2013
01 Sep 2013 Trial Update Astellas Pharma and FibroGen initiate a phase I pharmacokinetics trial in healthy volunteers in Germany (NCT02252731) Updated 26 Mar 2018
01 Sep 2013 Trial Update Astellas Pharma and FibroGen initiate a phase I trial in patients with hepatic impairment and healthy volunteers in Bulgaria (NCT02161224) Updated 26 Mar 2018
01 Sep 2013 Trial Update Astellas Pharma and FibroGen initiate a phase I trial in Healthy volunteers in Germany (NCT02161796) Updated 26 Mar 2018
01 Aug 2013 Trial Update Astellas Pharma initiates enrolment in a phase II trial for Anaemia (in non-haemodialysed patients with chronic kidney disease) in Japan (NCT01964196) Updated 24 Oct 2013
31 Jul 2013 Licensing Status Roxadustat licensed to AstraZeneca in USA, China & other major markets for Anaemia [6] Updated 01 Aug 2013
31 Jul 2013 Regulatory Status AstraZeneca & FibroGen intend to submit NDA to China FDA in 2015 [6] Updated 01 Aug 2013
31 Jul 2013 Regulatory Status AstraZeneca & FibroGen intend to submit NDA to US FDA in 2017 [6] Updated 01 Aug 2013
01 Jul 2013 Trial Update FibroGen completes a phase II trial in Anaemia in USA (NCT01147666) Updated 07 Oct 2014
30 Jun 2013 Trial Update Astellas initiates enrolment in a phase II trial for Anaemia (in haemodialysed patients with chronic kidney disease) in Japan (NCT01888445) Updated 11 Jul 2013
24 Jun 2013 Phase Change - III Phase-III clinical trials in Anaemia in Belgium & Poland (PO) Updated 08 Oct 2013
24 Jun 2013 Phase Change - III Phase-III clinical trials in Anaemia (in non-haemodialysed patients with chronic kidney disease) in Italy, Spain and United Kingdom (PO, tablet) (EudraCT 2012-005180-27) Updated 11 Jul 2013
31 May 2013 Phase Change - III Phase-III clinical trials in Anaemia (in non-haemodialysed patients with chronic kidney disease) in Romania and Russia after May 2013 (PO) Updated 15 Jan 2014
31 May 2013 Phase Change - III Phase III clinical trials for Anaemia in Hungary (in non-haemodialysed patients with chronic kidney disease) (PO, tablet) (NCT01887600) Updated 11 Jul 2013
01 May 2013 Phase Change - II Phase-II clinical trials in Anaemia (in chronic kidney disease patients on dialysis) in Japan (PO) (NCT01888445) Updated 19 Dec 2018
01 May 2013 Trial Update FibroGen completes a phase II trial in Anaemia in USA (NCT01414075) Updated 18 Jun 2014
31 Jan 2013 Trial Update FibroGen completes a phase II trial in Anaemia (in non-dialysed patients with chronic kidney disease) in China (NCT01599507) Updated 29 Nov 2013
01 Jan 2013 Trial Update FibroGen completes a phase II trial in Anaemia (in patients with end stage renal disease receiving haemodialysis) in China (NCT01596855) Updated 26 Mar 2018
11 Dec 2012 Phase Change - III Phase-III clinical trials in Anaemia in Europe (PO) Updated 13 Dec 2012
11 Dec 2012 Phase Change - III Phase-III clinical trials in Anaemia in USA (PO) Updated 13 Dec 2012
30 Nov 2012 Trial Update FibroGen initiates enrolment in the phase III ANDES trial for Anaemia (in chronic kidney disease patients not on dialysis) in Puerto Rico after November 2012(PO) (NCT01750190) Updated 12 Apr 2019
30 Nov 2012 Trial Update FibroGen initiates enrolment in a phase III trial for Anaemia (non-haemodialysis patients with chronic kidney disease) in USA (NCT01750190) Updated 16 Jan 2013
01 Nov 2012 Phase Change - III Phase-III clinical trials in Anaemia (in chronic kidney disease patients not on dialysis) in Philippines (PO) after November 2012 (NCT01750190) Updated 19 Jun 2015
01 Nov 2012 Phase Change - III Phase-III clinical trials in Anaemia (in chronic kidney disease patients not on dialysis) in Hong Kong, Malaysia, New Zealand, Singapore, Taiwan and Thailand (PO) (NCT01750190) Updated 26 Feb 2015
01 Sep 2012 Trial Update FibroGen completes a phase II trial in Anaemia (non-haemodialysis patients with chronic kidney disease) in USA and Puerto Rico (NCT01244763) Updated 07 Oct 2014
22 May 2012 Scientific Update Interim efficacy data from a phase II trial in Anaemia (haemodialysis patients with chronic kidney disease) presented at the 27th Annual Scientific Meeting of the American Society of Hypertension (ASH-2012) [79] Updated 06 Jun 2012
01 May 2012 Trial Update FibroGen initiates a phase II/III trial in Anaemia in USA and Puerto Rico (NCT01630889) Updated 08 Jul 2020
11 Jan 2012 Trial Update FibroGen completes enrolment in a phase II trial for Anaemia (non-haemodialysis patients with chronic kidney disease) in USA and Puerto Rico (NCT01244763) Updated 16 Jan 2013
15 Nov 2011 Phase Change - II Phase-II clinical trials in Anaemia in Singapore (PO) Updated 27 Sep 2012
15 Nov 2011 Phase Change - II Phase-II clinical trials in Anaemia in China (PO) Updated 18 Nov 2011
15 Nov 2011 Scientific Update Efficacy and adverse events data from a phase IIb trial in Anaemia released by FibroGen [78] Updated 18 Nov 2011
01 Sep 2011 Trial Update FibroGen initiates enrolment in a phase II trial in Anaemia (in patients with end stage renal disease receiving haemodialysis) in China (NCT01596855) Updated 26 Mar 2018
31 Jul 2011 Trial Update FibroGen initiates enrolment in a phase II trial for Anaemia in USA (NCT01414075) Updated 16 Aug 2011
01 Jul 2011 Phase Change - II Phase-II clinical trials in Anaemia in Hong Kong (PO) Updated 18 Jun 2014
04 May 2011 Scientific Update Interim efficacy, adverse events, and pharmacokinetic data from trials in Anaemia (haemodialysis patients with chronic kidney disease) released by FibroGen [167] Updated 06 May 2011
29 Mar 2011 Active Status Review FG 4592 is still in phase I trials for Anaemia (in patients with chronic kidney disease) in Japan and China [12] Updated 29 Mar 2011
29 Mar 2011 Phase Change - Discontinued(Preclinical) Discontinued - Preclinical for Sickle cell anaemia in USA (PO) Updated 29 Mar 2011
18 Mar 2011 Scientific Update Efficacy and adverse events data from a phase IIa trial in Anaemia (in patients with chronic kidney disease) released by FibroGen [12] Updated 23 Mar 2011
16 Nov 2010 Phase Change - II Phase-II clinical trials in Anaemia in Puerto Rico (PO) Updated 18 Nov 2011
21 Sep 2010 Regulatory Status Chinese State Food and Drug Administration (SFDA) approves Clinical Trial Application (CTA) for FG 4592 in Anaemia [120] Updated 22 Sep 2010
20 Sep 2010 Phase Change - I Phase-I clinical trials in Anaemia in China (PO) Updated 24 Nov 2010
01 Jun 2010 Trial Update FibroGen completes a phase I drug interaction trial in healthy volunteers in USA (NCT01376063) Updated 26 Mar 2018
01 Jun 2010 Trial Update FibroGen completes a phase II trial in Anaemia in USA (NCT00761657) Updated 09 Oct 2014
01 Jun 2010 Trial Update Astellas Pharma completes a phase I trial in Anaemia (patients with chronic kidney disease receiving haemodialysis) in Japan (NCT01083888) Updated 07 Oct 2014
01 Jun 2010 Trial Update Astellas Pharma completes a phase I trial in healthy volunteers in Japan (NCT00978198) Updated 07 Oct 2014
01 Mar 2010 Trial Update FibroGen initiates enrolment in a phase I drug interaction trial in healthy volunteers in USA (NCT01376063) Updated 26 Mar 2018
01 Feb 2010 Trial Update Astellas Pharma initiates a phase I trial in Anaemia (patients with chronic kidney disease receiving haemodialysis) in Japan (NCT01083888) Updated 26 Mar 2018
01 Sep 2009 Phase Change - I Phase-I clinical trials in Anaemia in Japan (PO) (NCT00978198) Updated 30 Sep 2009
29 May 2009 Phase Change - II Phase-II clinical trials in Anaemia in Europe (PO) Updated 13 Jul 2009
31 Jan 2009 Trial Update FibroGen resumes enrolment in a phase II trial for Anaemia in patients with chronic kidney disease not receiving dialysis in US Updated 03 Feb 2009
13 Nov 2007 Scientific Update Interim results from a Phase-II clinical trial in Anaemia added to the Haematological Disorders therapeutic trials section and preclinical data added to the Haematological Disorders pharmacodynamics section [168] Updated 13 Nov 2007
31 Mar 2007 Phase Change - Suspended(II) Suspended - Phase-II for Anaemia in USA (PO) Updated 27 Sep 2007
31 Dec 2006 Phase Change - II Phase-II clinical trials in Anaemia in USA (PO) Updated 27 Sep 2007
22 Aug 2006 Phase Change - Preclinical Preclinical trials in Sickle cell anaemia in USA (PO) Updated 27 Sep 2007
28 Apr 2006 Licensing Status FG 4592 has been licensed to Astellas Pharma in Europe, the Commonwealth of Independent States, the Middle East, and South Africa Updated 02 May 2006
16 Nov 2005 Phase Change - I Phase-I clinical trials in Anaemia in USA (PO) Updated 16 Nov 2005
24 Sep 2004 Licensing Status FibroGen has entered into an agreement with Yamanouchi to license FG 4592 in Japan for anaemia Updated 02 May 2006

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  95. An Open-label, Multicenter Study Investigating the Efficacy, Safety and Pharmacokinetics of Roxadustat (FG-4592) for Treatment of Anemia in Pediatric Patients With Chronic Kidney Disease

    ctiprofile
  96. Roxadustat Global Phase 3 Results for Treatment of Chronic Kidney Disease (CKD) Anemia to be Presented at American Society of Nephrology Kidney Week 2019.

    Media Release
  97. A Phase 3, Randomized, Open-Label, Active-Controlled Study to Evaluate the Efficacy and Safety of Roxadustat in the Maintenance Treatment of Anemia in End Stage Renal Disease Patients on Stable Dialysis

    ctiprofile
  98. FibroGen Announces New Roxadustat Data Presented at 2020 ERA-EDTA Virtual Congress.

    Media Release
  99. ASN Kidney Week 2018: Data Presented from Two Japanese Phase 3 Studies on Roxadustat in the Treatment of Anemia Associated with Chronic Kidney Disease in Patients on Dialysis.

    Media Release
  100. Astellas and FibroGen Announce Topline Results from Double-Blind Japan Phase 3 Study for Roxadustat in Hemodialysis Chronic Kidney Disease Patients with Anemia.

    Media Release
  101. A Phase 3, Multi-center, Randomized, 2-arm Parallel, Double-blind, Active-comparator (Darbepoetin Alfa) Conversion Study of Intermittent Oral Dosing of ASP1517 in Hemodialysis Chronic Kidney Disease Patients With Anemia

    ctiprofile
  102. A Phase 3, Multi-center, Randomized, 2-arm, Open-label Study of Intermittent Oral Dosing of ASP1517 in Erythropoiesis Stimulating Agent-naive Hemodialysis Chronic Kidney Disease Patients With Anemia

    ctiprofile
  103. A Phase 3, Long Term Study of Intermittent Oral Dosing of ASP1517 in Hemodialysis Chronic Kidney Disease Patients With Anemia Converted From Erythropoiesis Stimulating Agent Treatment

    ctiprofile
  104. FibroGen Announces Initiation by Astellas of Phase 3 Clinical Study in Japan of Roxadustat/ASP1517 for the Treatment of Anemia of Chronic Kidney Disease Triggering $10.0 Million Milestone Payment.

    Media Release
  105. A Phase 3, Multi-center, Open-label Study of Intermittent Oral Dosing of ASP1517 in Peritoneal Dialysis Chronic Kidney Disease Patients With Anemia

    ctiprofile
  106. Astellas and FibroGen Announce Positive Topline Results from First Japan Phase 3 Trial for Roxadustat in Chronic Kidney Disease Patients with Anemia.

    Media Release
  107. A Phase 3, Randomized, Open-Label, Active-Controlled Study of Efficacy and Safety of FG-4592 for Treatment of Anemia in Subjects With Chronic Kidney Disease on Dialysis

    ctiprofile
  108. A Phase 3, Open-Label, Randomized, Active-Controlled Study of the Efficacy and Safety of Roxadustat (FG-4592) in the Maintenance Treatment of Anemia in Subjects With End Stage Renal Disease (ESRD) on Stable Dialysis

    ctiprofile
  109. A Phase 3, Multicenter, Randomized, Open-Label, Active-Controlled Study of the Efficacy and Safety of FG-4592 in the Treatment of Anemia in Incident-Dialysis Patients

    ctiprofile
  110. FibroGen Presents Phase 3 Efficacy and Safety Results for Roxadustat Versus Epoetin Alfa as Treatment of Anemia in Incident Dialysis Patients with Chronic Kidney Disease.

    Media Release
  111. A Japanese, Phase 2, Multicenter, Randomized, 4-arm Parallel, Double-blind (Arms 1-3), Open-label (Arm 4), Active-comparator (Darbepoetin Alfa) Study of Intermittent Oral Dosing of ASP1517 in Hemodialysis-dependent Chronic Kidney Disease Patients With Anemia

    ctiprofile
  112. FibroGen to Present Roxadustat Clinical Data in Four Presentations at American Society of Nephrology - Kidney Week 2015.

    Media Release
  113. Phase 2 Data for Investigational Orally Active HIF-PHI Roxadustat (FG-4592) Show Anemia Correction in Incident Dialysis Chronic Kidney Disease Patients Regardless of Iron Repletion Status, Iron Supplementation Regimen, or Dialysis Modality.

    Media Release
  114. FibroGen Announces Results Showing That FG-4592, An Oral Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor (HIF-PHI), Corrects Anemia Without Intravenous Iron Supplementation in Incident Dialysis Patients.

    Media Release
  115. A Phase 2, Randomized, Open-Label, Dose Titration, Safety and Efficacy Study of FG-4592 for the Correction of Anemia in Newly Initiated Dialysis Patients Not on Erythropoiesis-Stimulating Agent Treatment

    ctiprofile
  116. A Phase 2, Randomized, Open-Label Active-Comparator (Epoetin Alfa) and Single-Blind Placebo-Controlled, Dose-Ranging Safety and Exploratory Efficacy Study of FG-4592 in Subjects With End-Stage Renal Disease Receiving Maintenance Hemodialysis

    ctiprofile
  117. FibroGen Reports Data from Phase 2 Study of FG-4592 Hemoglobin Correction and Maintenance in End-Stage Renal Patients.

    Media Release
  118. FibroGen Publishes Encouraging Phase 2 Anemia Data Demonstrating Roxadustats Ability to Maintain Hemoglobin Levels in Patients With Chronic Kidney Disease.

    Media Release
  119. A Phase 2, Randomized, Open-Label Active-Comparator (Epoetin Alfa) Dose-Ranging Safety and Exploratory Efficacy Study of FG-4592 in Subjects With End-Stage Renal Disease Receiving Maintenance Hemodialysis (HD)

    ctiprofile
  120. FibroGen Announces Chinese State FDA Approval of Phase 1 and 2 Development of FibroGen Oral Anemia Therapy, FG-4592.

    Media Release
  121. FibroGen Reports Fiscal 2016 Financial Results.

    Media Release
  122. A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Investigating the Efficacy and Safety of Roxadustat (FG-4592) for Treatment of Anemia in Patients With Lower Risk Myelodysplastic Syndrome (MDS) With Low Red Blood Cell (RBC) Transfusion Burden (LTB)

    ctiprofile
  123. Henry DH, Glaspy J, Harrup RA, Mittelman M, Zhou A, Bradley C, et al. Roxadustat (FG4592; ASP1517; AZD9941) in the Treatment of Anemia in Patients with Lower Risk Myelodysplastic Syndrome (LR-MDS) and Low Red Blood Cell (RBC) Transfusion Burden (LTB). ASH-Hem-2019 2019; abstr. 843.

    Available from: URL: https://ash.confex.com/ash/2019/webprogram/Paper128714.html
  124. FibroGen Announces Completion of Patient Enrollment in MATTERHORN, a Phase 3 Clinical Study of Roxadustat for the Treatment of Anemia in Patients with Lower Risk Transfusion-Dependent Myelodysplastic Syndromes (MDS).

    Media Release
  125. FibroGen Announces Results for MATTERHORN, a Phase 3 Clinical Study of Roxadustat for the Treatment of Anemia in Patients with Myelodysplastic Syndromes (MDS).

    Media Release
  126. Mittelman M, Henry DH, Glaspy J, Tombak A, Harrup RA, Madry K, et al. Efficacy and Safety of Roxadustat for Treatment of Anemia in Patients with Lower-Risk Myelodysplastic Syndrome (LR-MDS) with Low Red Blood Cell (RBC) Transfusion Burden: Results of Phase III Matterhorn Study. ASH-Hem-2023 2023; abstr. 195.

    Available from: URL: https://ash.confex.com/ash/2023/webprogram/Paper180749.html
  127. FibroGen Appoints Maykin Ho, Ph.D., to Board of Directors.

    Media Release
  128. A Phase 2/3 Trial of FG-4592 for Treatment of Anemia in Subjects With Lower Risk Myelodysplastic Syndrome

    ctiprofile
  129. FibroGen Announces China FDA Approval of CTA to Conduct Pivotal Phase 2/3 Clinical Trial of Roxadustat in Anemia Associated With Lower Risk MDS.

    Media Release
  130. FibroGen Reports Third Quarter 2023 Financial Results.

    Media Release
  131. FibroGen Announces Positive Topline Results from China Pivotal Phase 3 Clinical Trial of Roxadustat for the Treatment of Chemotherapy Induced Anemia.

    Media Release
  132. FibroGen Reports Second Quarter 2023 Financial Results.

    Media Release
  133. A Randomized, Open-label, Active-controlled, Multicenter Phase 3 Study to Investigate the Efficacy and Safety of Roxadustat for Treatment of Anemia in Subjects Receiving Chemotherapy Treatment for Non-Myeloid Malignancies

    ctiprofile
  134. Lu S, Wu J, Jiang J, Guo Q, Yu Y, Liu Y, et al. Roxadustat for chemotherapy-induced anemia in patients with non-myeloid malignancies: A randomized, open-label, active-controlled, phase III study. ESMO-2023 2023; abstr. LBA96.

    Available from: URL: https://oncologypro.esmo.org/meeting-resources/esmo-congress/roxadustat-for-chemotherapy-induced-anemia-in-patients-with-non-myeloid-malignancies-a-randomized-open-label-active-controlled-phase-iii-study
  135. A Phase 2 Open Label Study Investigating the Efficacy and Safety of Roxadustat (FG-4592) for Treatment of Anemia in Patients Receiving Chemotherapy Treatment for Non-Myeloid Malignancies

    ctiprofile
  136. FibroGen Announces Positive Topline Results from Phase 2 Clinical Trial of Roxadustat for the Treatment of Chemotherapy Induced Anemia.

    Media Release
  137. Glaspy JA, Gabrail NY, Locantore-Ford PA, Saha GC, Hardy E, Lee T, et al. Open-label, phase 2 study of roxadustat for treatment of anemia in patients receiving chemotherapy for non-myeloid malignancies. ASCO-2022 2022; abstr. 12085.

    Available from: URL: https://meetings.asco.org//abstracts-presentations/209829
  138. FibroGen Awarded Grant from National Heart, Lung, and Blood Institute to Develop HIF-PH Inhibitors to Treat Sickle Cell Disease.

    Media Release
  139. A Phase 1 Crossover Study to Assess the Relative Bioavailability of Roxadustat Following a Single Dose of Pediatric Azo Dye-free Tablet and Pediatric Azo Dye-free Mini-tablet (Solid and Suspension) Compared to a Single Dose of Azo Dye-containing Tablet in Healthy Adult Subjects

    ctiprofile
  140. A Phase 1 Study to Evaluate the Pharmacokinetics of Roxadustat in Subjects With Different Degrees of Renal Function

    ctiprofile
  141. Pharmacokinetic Study of ASP1517 - Evaluation of the Effect of Lanthanum Carbonate Hydrate on the Pharmacokinetics of ASP1517 in Non-elderly Healthy Adult Male Subjects.

    ctiprofile
  142. ASP1517 Pharmacokinetic Study - Evaluation of Food Effect on the Pharmacokinetics of ASP1517

    ctiprofile
  143. Pharmacokinetic Study of ASP1517 - Evaluation of the Effect of Kremezin® on the Pharmacokinetics of ASP1517 in Non-elderly Healthy Adult Male Subjects, When Administered Concomitantly or in a Time Separated Manner.

    ctiprofile
  144. A Phase 1, Double-blind, Randomized, Placebo-controlled, 4-way Crossover Study to Evaluate the Dose-proportionality and Pharmacokinetics of FG-4592 in Healthy Young and Elderly Male and Female Subjects

    ctiprofile
  145. A Phase 1, Non-randomized, Open-label, Single-dose Study to Investigate the Pharmacokinetics, Safety and Tolerability of FG-4592 in Subjects With Moderate Hepatic Impairment and Healthy Subjects With Normal Hepatic Function

    ctiprofile
  146. A Phase 1, Open-label, One-sequence Crossover Study to Evaluate the Effect of Multiple Doses of FG 4592 on the Pharmacokinetics of Warfarin in Healthy Subjects

    ctiprofile
  147. ASP1517 Clinical Pharmacological Study Examination of Pharmacokinetics and Pharmacodynamics in Patients With Renal Anemia Undergoing Hemodialysis

    ctiprofile
  148. ASP1517 Phase 1 Clinical Study - Single and Multiple Oral Dosing of ASP1517 in Healthy Non-elderly Male Volunteers

    ctiprofile
  149. A Phase 1, Single-Center, One-Sequence, Open-Label Study to Investigate the Interaction Between FG-4592 and Rosiglitazone in Healthy Adult Subjects

    ctiprofile
  150. FibroGen Provides Update on the Development of FG-2216 and FG-4592, Oral Therapies for Anemia.

    Media Release
  151. FibroGen Announces Receipt of Milestone Payment from AstraZeneca for Successful Completion of Long-Term Pre-Clinical Safety Studies of Roxadustat.

    Media Release
  152. FibroGen Reports UK Court Ruling.

    Media Release
  153. European Patent Office Maintains FibroGen Patent Relating to Hypoxia-Inducible Factor (HIF) Prolyl Hydroxylase Inhibitor Technology.

    Media Release
  154. Akebia Prevails in European Patent Dispute and Preserves Access to Key Market for Vadadustat.

    Media Release
  155. FibroGen Reports Fourth Quarter and Full Year 2020 Financial Results.

    Media Release
  156. Fishbane S, Provenzano R, Rastogi A, Coyne D, Pecoits-Filho R, Charytan C, et al. Roxadustat Lowers Risk of RBC Transfusion in Patients with Anemia of CKD. ASH-Hem-2020 2020; abstr. 748.

    Available from: URL: https://ash.confex.com/ash/2020/webprogram/Paper140862.html
  157. Fishbane S, Provenzano R, Szczech L, Leong R, Saikali K, Zhong M, et al. Pooled Efficacy and Cardiovascular Safety Results of Roxadustat Compared with Epoetin Alfa in the Treatment of Anemia in Chronic Kidney Disease Patients on Dialysis. ASH-Hem-2020 2020; abstr. 749.

    Available from: URL: https://ash.confex.com/ash/2020/webprogram/Paper141053.html
  158. FibroGen Reports First Quarter 2020 Financial Results.

    Media Release
  159. Year-to-date and Q3 2019 results. Internet-Doc 2019;.

    Available from: URL: https://www.astrazeneca.com/content/dam/az/PDF/2019/q3/Year-to-date_and_Q3_2019_Results_announcement.pdf
  160. Roxadustat Phase III Program Pooled Analyses Showed Positive Efficacy and No Increased Cardiovascular Risk in Patients with Anemia from Chronic Kidney Disease Versus Comparators.

    Media Release
  161. FibroGen Reports Second Quarter 2019 Financial Results.

    Media Release
  162. Pooled analyses of the roxadustat global Phase III programme confirmed cardiovascular safety.

    Media Release
  163. FibroGen Announces Positive Topline Results from Pooled Safety Analyses of Roxadustat Global Phase 3 Program.

    Media Release
  164. FibroGen Announces Analysis of Peritoneal Dialysis Patients With Chronic Kidney Disease From Roxadustat (FG-4592) Incident Dialysis Study.

    Media Release
  165. FibroGen Reports Proof-of-Principle for Oral Anemia Therapy FG-4592 in Hemodialysis Patients Switched from Intravenous rhEPO in an Active-Controlled Randomized Phase 2 Study.

    Media Release
  166. FibroGen Announces New Research in HIF and CTGF Therapeutic Programs Presented at the Annual Meeting of the American Society of Nephrology.

    Media Release
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