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Sarilumab - Regeneron/Sanofi

Drug Profile

Sarilumab - Regeneron/Sanofi

Alternative Names: Anti-IL 6 receptor antibody; Anti-interleukin 6 receptor antibody; Kevzara; REGN-88; SAR-153191

Latest Information Update: 29 Apr 2020

At a glance

  • Originator Regeneron Pharmaceuticals; sanofi-aventis
  • Developer Asahi Kasei Pharma Corp; Regeneron Pharmaceuticals; Sanofi
  • Class Anti-inflammatories; Antirheumatics; Antivirals; Monoclonal antibodies
  • Mechanism of Action Interleukin 6 receptor antagonists
  • 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 Rheumatoid arthritis
  • Phase III Giant cell arteritis; Polymyalgia rheumatica
  • Phase II/III COVID 2019 infections
  • Phase II Juvenile rheumatoid arthritis; Uveitis
  • Discontinued Ankylosing spondylitis

Most Recent Events

  • 27 Apr 2020 Efficacy and adverse events data from a phase-II/III clinical trials in COVID-2019 infections released by Regeneron Pharmaceuticals and Sanofi
  • 15 Apr 2020 Sanofi and Regenerone suspend a phase III trials in Polymyalgia rheumatica (Combination therapy) in Argentina, Australia, Belgium, Canada, Canada, Estonia, France, Germany, Hungary, Israel, Italy, Japan, Switzerland, Spain, United Kingdom, Russia, Netherlands (SC) (NCT03600818) (EudraCT2017-002989-42)
  • 26 Mar 2020 Phase-II/III clinical trials in COVID-2019 infections in Germany, France, Italy, Spain, Russia, Canada (IV) (EudraCT2020-001162-12)

Development Overview

Introduction

Sarilumab, a fully-human antibody targeting the interleukin-6 receptor (IL-6R), is collaboratively being developed by Regeneron Pharmaceuticals and Sanofi (formerly sanofi-aventis) for the treatment of rheumatoid arthritis (RA), giant cell arteritis, juvenile rheumatoid arthritis, polymyalgia rheumatica, non-infectious uveitis and COVID-19 infections. The antibody candidate is the first from Regeneron's VelocImmune® platform to enter clinical development. IL-6 is a signalling protein widely involved in the regulation of immune and inflammatory responses and has been shown to be a key mediator of inflammation in RA. Sarilumab has a high-affinity to the α-subunit of both the soluble and membrane-bound IL-6R and blocks the binding of IL6 to its receptor, interrupting cytokine mediated inflammatory signalling cascade. The drug is available in Japan, Canada, the US, Germany, Netherlands, France and the UK and is approved in rest of EU for rheumatoid arthritis, both as an adjunctive treatment and as a monotherapy. Clinical development is ongoing for non-infectious uveitis, polymyalgia rheumatica, giant cell arteritis and juvenile idiopathic arthritis in countries worldwide. Clinical development for COVID-2019 infections is underway in the US, Canada, France, Germany, Italy, Japan, Russia and Spain .

Sarilumab was also being developed for the treatment of ankylosing spondylitis; however, the development in the indication was discontinued because of lack of efficacy in the phase II trials.

Regeneron and Sanofi are also developing other antibody candidates under this collaboration [see AdisInsight Drug profile 800035624].

sanofi-aventis changed its name to Sanofi in May 2011 [1] .

As at November 2017, no recent reports of development had been identified for phase-I development in Rheumatoid-arthritis in Moldova (SC, Injection).

Company Agreements

As of April 2020, Regeneron Pharmaceuticals expanded the agreement with the US Department of Health and Human Services (HHS) to fund certain research and development activities related to COVID-19 treatments, including REGN COV2 and the US phase II/III trial Kevzara study. Earlier, in March 2020, Biomedical Advanced Research and Development Authority (BARDA) within the US Department of Health and Human Services Office of the Assistant Secretary for Preparedness and Response (ASPR) will provide support for a US phase II/III trial to evaluate sarilumab for the treatment of COVID-2019 infections. [2] [3]

In April 2020, Sanofi finalized the restructuring of the antibody collaboration with Regeneron. Under the final restructured agreement, Sanofi will have sole responsibility for alirocumab outside the US while Regeneron will have sole responsibility of the candidate in the US. Each company will supply alirocumab in its respective territory. Earlier in December 2019, Sanofi and Regeneron Pharmaceuticals announced their intention to simplify antibody collaboration for sarilumab and alirocumab by restructuring into a royalty-based agreement. In November 2009, Regeneron and sanofi-aventis entered an agreement to expand and extend a previous agreement (signed in November 2007) for the discovery, development and commercialisation of fully-human therapeutic antibodies utilising Regeneron's proprietary VelociSuite of technologies (including VelocImmune®). Sanofi-aventis has the exclusive option to co-develop each drug candidate, where development costs will be shared. Regeneron has the right to co-promote all products worldwide. In the US, profits will be shared equally; outside of the US, profits will be split on a sliding scale with sanofi-aventis' share ranging from 65% to 55%. Regeneron will be entitled to receive up to $US250 million in sales milestones when the collaboration achieves certain aggregate annual sales outside the US, starting at $US1 billion. Under the terms of the original agreement, sanofi-aventis made an upfront payment of $US85 million to Regeneron. . [4] [5] [6] [7] [8] [9]

In December 2017, Sanofi and Asahi Kasei Pharma entered into a licensing agreement for the commercialisation of sarilumab used for the treatment of rheumatoid arthritis in Japan. According to the terms of the agreement, Asahi Kasei Pharma will market, promote, and distribute the drug canditate. Additionally Sanofi and Regeneron will manufacture and Sanofi will co-promote the product. [10]

Key Development Milestones

Rheumatoid arthritis (RA)

In February 2018, Asahi Kasei Pharma launched 150mg syringe and 200mg syringe subcutaneous injection of sarilumab in Japan [11] .

As at December 2017, sarilumab is available in the US for the treatment of adult patients with moderately to severely active rheumatoid arthritis who have an inadequate response or intolerance to one or more biologic or non-biologic Disease-Modifying Anti-Rheumatic Drugs (DMARDs) [10] . In May 2017, Sanofi and Regeneron had received approval for sarilumab from the US FDA. Sarilumab may be used as monotherapy or in combination with methotrexate or other conventional DMARDs. The recommended dosage of Kevzara is 200mg once every two weeks given as a subcutaneous injection. The dosage can be reduced from 200mg to 150mg once every two weeks, as needed, to help manage certain laboratory abnormalities. The approval was based on data from approximately 2 900 adults with moderately to severely active RA who had an inadequate response to previous treatment regimens. In the US, sarilumab will be marketed by Regeneron and Sanofi Genzyme [12] . In October 2016, the US FDA issued a Complete Response Letter (CRL) regarding the Biologics License Application (BLA) for sarilumab. The CRL did not identify any concerns relating to the safety or efficacy of sarilumab. The letter referred to certain deficiencies identified during a routine good manufacturing practice inspection of the Sanofi Le Trait facility in France where sarilumab is filled and finished. Sanofi submitted a comprehensive corrective action plan to the FDA and is implementing the corrective actions specified in that plan. Sanofi is working closely with the FDA towards a timely resolution that addresses these concerns. In April 2017, the USFDA accepted the resubmission of the sarilumab Biologics License Application (BLA) as a Class I response with a two month review timeline, with the new Prescription Drug User Fee Act (PDUFA) action date set for May 22, 2017. This resubmission will be subjected to successful completion of an inspection by FDA of Sanofi's Le Trait fill and Finish facility, with an anticipated action date in the second quarter [13] [14] [15] [16] . It was reported in January 2016, that the BLA seeking approval of sarilumab for the treatment of rheumatoid arthritis had been accepted for review by the US FDA. The BLA was submitted by the third quarter of 2015, and included data from the phase III SARIL-RA programme [17] [18] [19] .

As at December 2017, sarilumab is available in the UK, Germany, Nehterlands and France for the treatment of adult patients with moderately to severely active rheumatoid arthritis who have an inadequate response or intolerance to one or more biologic or non-biologic Disease-Modifying Anti-Rheumatic Drugs (DMARDs) [10] . In June 2017, the European Commission had granted marketing authorisation for sarilumab. In April 2017, Committee for Medicinal Products for Human Use (CHMP) of the EMA adopted a positive opinion for the marketing authorisation of sarilumab, recommending its approval for use in adult patients with moderately to severely active rheumatoid arthritis. The positive opinion was based on the seven phase III trials of the global SARIL-RA clinical development programme, which include the trials SARIL-RA-MOBILITY, SARIL-RA-TARGET and SARIL-RA-MONARCH [see below], and data covering over 3 300 adults with moderate-to-severe RA, most of whom have responded inadequately to disease-modifying anti-rheumatic drugs (DMARDs) or anti-tumour necrosis factor alpha (anti-TNFα). The application was accepted for review by the EMA in July 2016 [20] [21] [22] [23] .

In September 2017, the Pharmaceuticals and Medical Devices Agency (PMDA) in Japan approved sarilumab for the treatment of adult patients with rheumatoid arthritis who have had an inadequate response to conventional treatments [24] . In October 2016, Regeneron Pharmaceuticals submitted an application for marketing approval for sarilumab, in Japan [25] .

In February 2017, Sanofi Genzyme announced that sarilumab (KevzaraTM) is available in Canada for the treatment of adult patients with moderately to severely active rheumatoid arthritis who have an inadequate response or intolerance to one or more biologic or non-biologic Disease-Modifying Anti-Rheumatic Drugs (DMARDs) [26] [27] . In January 2017, Regeneron and Sanofi received the first approval for sarilumab from Health Canada [28] . Sarilumab should be used in combination with methotrexate or other traditional DMARDs, or may be given as monotherapy in cases of intolerance or contraindication to methotrexate or DMARDs. The recommended dose of sarilumab is 200mg once every two weeks given as a subcutaneous injection; dosage can be reduced from 200mg to 150mg once every two weeks to help manage certain laboratory abnormalities. The approval was based on the data from seven studies of the SARIL-RA clinical programme, which includes the trials SARIL-RA-MOBILITY, SARIL-RA-TARGET and SARIL-RA-MONARCH [see below], and data covering over 2 900 adults with moderate-to-severe rheumatoid arthritis. The drug is expected to be marketed by Sanofi Genzyme in Canada [15] [14] .

In June 2018, long-term safety data (5-year follow-up) from six different clinical trials (TARGET, NCT01709578; MOBILITY, NCT01061736; NCT01764997; NCT01768572; NCT02057250; NCT01217814 and also those who continued into extension trials) was presented at the 19th Annual Congress of the European League Against Rheumatism (EULAR-2018) [29] .

Regeneron and Sanofi have initiated a global phase III programme for sarilumab called the SARIL-RA programme, intended to evaluate the safety and efficacy of sarilumab, as a monotherapy or in combination with conventional DMARDs, including methotrexate (MTX), to reduce the signs and symptoms, improve physical function and inhibit the radiographic progression of RA. The first study in the programme was the phase IIb/III SARIL-RA-MOBILITY trial in 1 675 patients with rheumatoid arthritis which began in March 2010 (NCT01061736; EudraCT2009-016266-90). The trial was conducted in the US, Argentina, Australia, Austria, Belarus, Belgium, Brazil, Canada, Chile, Colombia, Czech Republic, Egypt, Estonia, Finland, Germany, Greece, Hungary, India, South Korea, Lithuania, Malaysia, Mexico, Netherlands, New Zealand, Norway, Philippines, Poland, Portugal, Romania, Russia, South Africa, Spain, Taiwan, Thailand, Turkey and Ukraine. This study was completed in October 2013 and met all three of its co-primary endpoints [30] [31] . In both parts, the primary endpoint was the proportion of patients achieving 20% improvement by American College of Rheumatology criteria (ACR20). Results were reported in June 2014 [32] [33] [34] [35] [36] . Pharmacodynamics results from the study were presented by the company at the 80th American College of Rheumatology (ARH-2016) and at the 51st Annual Meeting of the Association of Rheumatology and Health Professionals (ARHP-2016) in November 2016 [37] .

In May 2015, Regeneron and Sanofi announced that the second global phase III trial called SARIL-RA-TARGET in 546 patients who did not respond or were intolerant to anti-TNF therapy, met the co-primary efficacy endpoints of a greater improvement in signs and symptoms of rheumatoid arthritis at 24 weeks and physical function at 12 weeks, compared with placebo (NCT01709578; EudraCT2011-003538-16) [38] . In this double blind trial, patients received single doses of sarilumab (150mg or 200mg) or placebo in combination with non-biologic disease modifying anti-rheumatic drugs (DMARD) therapy. The trial was initiated in the US in October 2012, and has expanded to Argentina, Australia, Austria, Brazil, Canada, Chile, Colombia, the Czech Republic, Ecuador, Germany, Greece, Hungary, Italy, Lithuania, Mexico, New Zealand, Peru, Poland, Portugal, Romania, Russia, Slovakia, Spain, Taiwan, Turkey and Ukraine. Sanofi completed the trial in April 2015. Trial results were presented at the 79th Annual Scientific Meeting of the American College of Rheumatology [39] [40] [41] .

In May 2015, Regeneron and Sanofi reported that the phase III trial called SARIL-RA-EASY met its primary endpoint of no technical failure with the sarilumab auto-injection device compared with pre-filled syringes [38] . The trial, which was completed in March 2016, was a usability study of the sarilumab auto-injector device in 217 patients with moderate to severe active rheumatoid arthritis (NCT02057250; EudraCT2012-004339-21). The open-label trial was conducted in the US, Chile, Mexico, Poland, Russia and South Africa [42] .

As reported by Regeneron and Sanofi, the phase III SARIL-RA-ASCERTAIN trial met its primary endpoint [38] . The trial, which was completed in October 2014, compared the tolerability of sarilumab versus tocilizumab, both in combination with methotrexate, in patients with moderate to severe rheumatoid arthritis and inadequate response to TNF-α antagonists (SFY13370; EudraCT2012-003536-23; U1111-1133-7839; NCT01768572). The randomised, double-blind trial was initiated in March 2013 and enrolled 202 patients in the US, Belgium, Czech Republic, Estonia, Finland, Hungary, Norway, the Netherlands, the UK, Poland, Spain and Sweden [43] . In June 2019, results from the study were presented at the 20th Annual Congress of the European League Against Rheumatism (EULAR-2019) [44] .

In November 2016, Sanofi completed the phase III SARIL-RA-HARUKA trial which evaluated the safety and efficacy of sarilumab added to non-methotrexate disease modifying anti-rheumatic drugs including sulfasalazine, leflunomide, bucillamine, tacrolimus, or mizoribin or as monotherapy in Japanese patients with rheumatoid arthritis (NCT02373202; LTS13618; U1111-1160-6525). The randomised, double-blind trial initiated in February 2015, enrolled 91 patients in Japan [45] .

In February 2015, Sanofi terminated the phase III RA-COMPARE trial due to difficulty in operational feasibility, delay incurred and failure in obtaining timely results, the decision was not based on any safety related issues (NCT01764997; EudraCT2012-001984-66). The randomised, double-blind trial was initiated in April 2013 and investigated the efficacy and tolerability of sarilumab plus methotrexate, compared with etanercept plus methotrexate in patients with rheumatoid arthritis not responding to adalimumab plus methotrexate. The trial enrolled 452 patients out of 700 patients planned from sites in the US, Europe, the Middle East, South America, Australia, New Zealand, Asia and South Africa [34] [46] .

In January 2015, Sanofi and Regeneron initiated the phase III SARIL-RA-MONARCH trial which met the primary endpoint of statistically significant difference in DAS28-ESR score from baseline at week 24, in patients with rheumatoid arthritis (EFC14092; U1111-1160-6154; NCT02332590; EudraCT2014-002541-22). The trial evaluated safety and efficacy of sarilumab monotherapy, compared with adalimumab monotherapy. The trial intends to enrol approximately 369 patients in the US, Chile, Czech Republic, Germany, South Korea, Peru, Poland, Romania, Russia, South Africa, Spain, Ukraine, in the UK and Hungary, who are either intolerant to or inappropriate for methotrexate therapy, or those who are deemed inadequate responders following 12 weeks of treatment with methotrexate. The companies released positive top-line results from the phase III trial in March 2016 and November 2016. In November 2017, updated safety and efficacy results were presented at the 81st American College of Rheumatology and the 52nd Association of Rheumatology Health Professionals Annual Scientific Meeting. Updated results from the trial were presented at the 19th Annual Congress of the European League Against Rheumatism (EULAR-2018), in June 2018. In June 2019, Regeneron presented efficacy and safety data from the open-label extension study at the 20th Annual Congress of the European League Against Rheumatism (EULAR-2019) [47] [48] [49] [50] [51] [52] [53] .

In Sanofi initiated a phase III long-term follow-up trial (ABILITY; RA-EXTEND; SARIL-RA-EXTEND) to investigate the long-term safety and efficacy of sarilumab in patients with rheumatoid arthritis who received disease-modifying antirheumatics in the MOBILITY trial (NCT01146652; EudraCT2010-019262-86). The trial is also open to patients who complete the TARGET and ASCERTAIN studies, and is expected to recruit approximately 2000 patients in the US, Argentina, Australia, Austria, Belarus, Belgium, Brazil, Canada, Chile, Colombia, Czech Republic, Ecuador, Egypt, England, Estonia, Finland, Germany, Greece, Guatemala, Hong Kong, Hungary, India, Israel, Italy, Lithuania, Malaysia, Mexico, Netherlands, New Zealand, Norway, Peru, Philippines, Poland, Portugal, Romania, Russia, Scotland, Slovakia, South Africa, South Korea, Spain, Sweden, Switzerland, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, USA
[34] . The primary outcome is the number of patients with adverse events. The estimated study completion date is in August 2015 [54] . In December 2016, results from the trial were presented at 80th American College of Rheumatology and the 51st Annual Meeting of the Association of Rheumatology and Health Professionals (ACR/ARHP - 2016) [55] .

In October 2016, Sanofi and Regeneron completed the phase III SARIL-RA-KAKEHASI study, which assessed the safety and efficacy of sarilumab as an add-on therapy to methotrexate in patients with moderate to severely active rheumatoid arthritis, who are inadequate responders to methotrexate therapy (NCT02293902; EFC14059; U1111-1155-7401). This randomised, double-blind, placebo-controlled study was initiated in November 2014 and enrolled 243 patients in Japan [56] .

Sanofi and Regeneron completed the phase III SARIL-RA-ONE study in May 2015 that investigated the immunogenicity and safety of sarilumab when administered as monotherapy to patients with moderate to severe rheumatoid arthritis (EFC13752; U1111-1143-4344; EudraCT2013-002790-22; NCT02121210). The open-label, randomised study was initiated in June 2014 and enrolment 132 patients the US, the Czech Republic, Estonia, Chile, Poland, Russia and Hungary [57] .

A phase II trial of sarilumab in patients receiving methotrexate enrolled 250 patients in the US, Brazil, Canada, Colombia, the Czech Republic, Germany, Hungary, Italy, Mexico, Norway and Spain (NCT01217814; EudraCT2010-021020-94). However, the trial was terminated in September 2011, as delays would not have allowed the trial to be completed within a reasonable timeframe [58] .

In March 2016, Regeneron and Sanofi completed a phase I drug-interaction trial that evaluated the effects of sarilumab on the pharmacokinetics of simvastatin, in patients with rheumatoid arthritis (NCT02017639). The study enrolled 19 patients in the US, South Korea and Moldova [59] .

A phase I trial investigating the safety and tolerability of sarilumab, in combination with methotrexate, in Japanese patients with rheumatoid arthritis was completed in December 2013 (TDU13402; U1111-1134-0048; NCT01850680). The study enrolled 61 patients in Japan, and was initiated in April 2013 [60] .

Initial clinical trials of sarilumab in patients with rheumatoid arthritis began in 2008 [61] . Three phase I trials that began in 2008 were completed in 2009 in the US (NCT01055899, NCT01011959) and Russia (NCT01026519). The trials found sarilumab to be well tolerated by patients with rheumatoid arthritis, with no dose limiting toxicities observed [62] [63] [64] [65] .

In May 2015, Regeneron completed a phase I trial, in collaboration with Sanofi, which was designed to assess the pharmacodynamic effects, safety and pharmacokinetics of single doses of sarilumab and tocilizumab in patients with rheumatoid arthritis (NCT02097524). Patients will be on background methotrexate therapy. The trial was initiated in March 2014 and enrolled 105 patients in the US and was completed in April 2015 [66] .

A phase I trial to assess the safety and pharmacokinetics of two formulations of sarilumab in patients with rheumatoid arthritis was completed in September 2011 (NCT01328522). The randomised, parallel-assignment, single-blind trial enrolled 32 patients in the US [67] .

Sanofi, in March 2016, completed a phase I trial that evaluated the safety and tolerability of sarilumab, administered subcutaneously, in patients with rheumatoid arthritis, compared with tocilizumab (NCT02404558). The randomised, open-label trial enrolled 30 patients in Japan [68] .

COVID-2019 infections

In March 2020, Sanofi initiated and dosed the first patient in a phase II/III trial to evaluate efficacy and safety of intravenous injection of sarilumab for hospitalised patients with COVID-2019 infections (EudraCT2020-001162-12; NCT04327388; U1111-1249-6021; EFC16844). The randomised, double-blind, placebo-controlled trial intends to enrol approximately 300 patients in Canada, France, Germany, Italy, Japan, Russia, Spain and may expand to Israel [69] .

In March 2020, Regeneron and Sanofi alongwith The Feinstein Institutes for Medical Research, initiated phase II/III trial to evaluate the safety and efficacy of intravenous injection of sarilumab in adults hospitalised with serious complications from COVID-2019 (6R88COV2040; NCT04315298). The randomised trial intends to enrol approximately 400 patients in the US [70] [71] [72] [73] . In April 2020, Sanofi and Regeneron Pharmaceuticals released preliminary results from the phase II portion of the trial. The companies also announced that following a review of all available phase II and phase III data, the Independent Data Monitoring Committee has recommended that the trial will be immediately amended so that only "critical" patients continue to be enrolled to receive sarilumab 400 mg or placebo and the lower dose of the drug 200 mg will be discontinued [74] [72] .

Giant cell arteritis

In April 2020, Sanofi and Regeneron suspended a phase III trial due to COVID-19 (EFC15068; U1111-1200-2184; EudraCT2017-002988-18; NCT03600805). The trial was initiated in August 2018 to evaluate the efficacy of sarilumab in combination with prednisone, in patients with giant cell arteritis. The randomised, double blind trial intends to enrol approximately 360 patients in the US, Argentina, Australia, Austria, Belgium, Canada, Croatia, Denmark, Estonia, Finland, France, Germany, Hungary, Israel, Italy, Netherlands, Portugal, Russia, Scotland, Slovenia, Spain, Sweden, Switzerland, UK [75] .

Juvenile rheumatoid arthritis: In February

2020, Sanofi and Regenerone announces intention to submit a regulatory application for systemic juvenile rheumatoid arthritis in 2023 or later [76] .

In August 2018, Regeneron resumed recruitment in phase II trial. Earlier, in December 2017, Sanofi suspended a phase II trial since they have decided to amend the current protocol, in order to optimise the study design and procedures (DRI13926; U1111-1177-3584; EudraCT2015-004000-35; NCT02991469). The open-label, sequential, ascending, repeated dose-finding study was initiated, in September 2016, to evaluate the pharmacokinetics, pharmacodynamics, efficacy and safety of sarilumab SC in patients with systemic juvenile idiopathic arthritis. The trial intended to enrol 36 patients in Spain, Estonia, France, Russia, Finland, Italy, the Netherlands, the UK, Germany, Czech Republic, Chile, Canada, Argentina, Poland and the US [77] .

In June 2016, Sanofi initiated an open-label phase II trial of sarilumab administered as a subcutaneous injection in children and adolescents with polyarticular juvenile idiopathic arthritis (DRI13925; U1111-1177-3487; EudraCT2015-003999-79; NCT02776735; P067-2013). The trial will assess the pharmacokinetic profile of sarilumab to identify dose and regimen for further development of the product in this population. The ascending, dose-finding trial intends to enrol 72 subjects in the UK, Russia, Poland, the Netherlands, Mexico, Italy, Finland, Estonia, Czech Republic, Chile, Germany, the US, Argentina, Canada, France and Spain [78] .Results from the trial were presented at the 20th Annual Congress of the European League Against Rheumatism (ELAR-2019) [79] .

Polymyalgia rheumatica

In April 2020, Sanofi and Regeneron suspended a phase III trial which was designed to evaluate the efficacy and safety of sarilumab, in patients with polymyalgia rheumatica (EFC15160; U1111-1201-0777; EudraCT2017-002989-42; NCT03600818). The trial was suspended due to pandemic COVID-2019 infections. Evaluation of the proportion of patients achieving sustained remission is the defined primary endpoints of the trial. The double-blind, randomised trial was initiated in August 2018 and intends to enrol approximately 280 patients in Argentina, Australia, Belgium, Canada, Estonia, France, Germany, Hungary, Israel, Italy, Japan, Netherlands, Russia, Spain, Switzerland, the UK and the US [80] .

Uveitis

Sanofi and Regeneron completed the phase II SARILNIUSATURN trial in April 2016, which evaluated the efficacy of sarilumab in patients with non-infectious uveitis (SARIL-NIU-SATURN; ACT13480; U1111-1130-6500; EudraCT 2012-004845-34; NCT01900431). Sarilumab was dosed every 2 weeks, with background therapy continuing. The primary endpoint was percentage of patients with either a ≥2-step reduction in vitreous haze, or the use of prednisone <10mg/day, at 16 weeks. The randomised, double-blinded trial in July 2013, enrolled 58 patients in the US, the Czech Republic, Germany, France, Italy, Spain and Turkey [81] [82] .

Ankylosing spondylitis

A phase II trial of sarilumab in patients with ankylosing spondylitis was conducted by Regeneron and Sanofi-Aventis in the US, Canada, Australia, Austria, Belgium, the Czech Republic, France, Germany, Hungary, Lithuania, Netherlands, Poland, Spain and Turkey (ALIGN; NCT01061723; EudraCT2009-016068-35). The trial did not meet its primary endpoint. The trial, completed in June 2011, enrolled a total of 300 subjects. In the randomised, double-blind trial, patients received placebo or sarilumab 100mg or 150mg once a week or 100mg, 150mg or 200mg every other week by subcutaneous injection for 12 weeks. The primary endpoint was the proportion of patients achieving the assessment in the Ankylosing Spondylitis International Working Group criteria for 20% improvement (ASAS20) [35] [83] . A long-term extension study of ALIGN was recruiting subjects by invitation only, however, it was discontinued in January 2012 for lack of benefit on efficacy (NCT01118728; EudraCT2010-019263-11). It appears that the development of sarilumab for ankylosing spondylitis has been discontinued [84] .

Labelling information

The label for sarilumab carries a boxed warning for increased risk of developing serious infections that may lead to hospitalisation or death [28] .

Patent Information

As at February 2018, Regeneron Pharmaceuticals reported that it has composition of matter patents covering sarilumab in the US (7 582 298) and the EU (2 041 177) that will expire in January 2028 and June 2027, respectively. Sarilumab is also covered under a formulation related patent in the US (9 173 880) which is expected to expire in December 2031 and methods of treatment related patents in the US (8 080 248) and the EU (2 766 039) that are set to expire in June 2027 and October 2032, respectively [85] .

Sarilumab has patent protection until 2028 in the US, and until 2027 in the EU and Japan.

Drug Properties & Chemical Synopsis

  • Route of administration IV, SC
  • Formulation Injection
  • Class Anti-inflammatories, Antirheumatics, Antivirals, Monoclonal antibodies
  • Target Interleukin 6 receptor
  • Mechanism of Action Interleukin 6 receptor antagonists
  • WHO ATC code

    J05A-X (Other antivirals)

    L04A-C14 (Sarilumab)

    M01 (Antiinflammatory and Antirheumatic Products)

    S01B-C (Antiinflammatory agents, non-steroidals)

  • EPhMRA code

    J5B (Antivirals, excluding anti-HIV products)

    L4 (Immunosuppressants)

    M1 (Anti-Inflammatory and Anti-Rheumatic Products)

    S1R (Ophthalmic Non-steroidal Anti-Inflammatories)

  • Chemical name Immunoglobulin G1, anti-(human interleukin 6 receptor α)(human REGN88 heavy chain), disulfide with human REGN88 light chain, dimer
  • Molecular formula C6388 H9918 N1718 O1998 S44
  • CAS Registry Number 1189541-98-7

Biomarkers Sourced From Trials

Indication Biomarker Function Biomarker Name Number of Trials

ankylosing spondylitis

Outcome Measure

Ubiquinone-2

sphingolipid transporter 1 (putative)

CRP

1

1

1

juvenile rheumatoid arthritis

Exclusion

interleukin 6 receptor

IL6

2

2

juvenile rheumatoid arthritis

Outcome Measure

interleukin 6 receptor

IL6

CRP

2

2

2

rheumatoid arthritis

Exclusion

metaxin 1

1

rheumatoid arthritis

Inclusion

metaxin 1

CRP

1

5

rheumatoid arthritis

Outcome Measure

Uric acid

TNF-alpha

metaxin 1

growth hormone 1

CRP

A1C

2

1

2

1

7

2

Biomarker

Drug Name Biomarker Name Biomarker Function
Sarilumab - Regeneron/Sanofi A1C Outcome Measure
CRP Inclusion, Outcome Measure
growth hormone 1 Outcome Measure
IL6 Exclusion, Outcome Measure
interleukin 6 receptor Exclusion, Outcome Measure
metaxin 1 Exclusion, Inclusion, Outcome Measure
sphingolipid transporter 1 (putative) Outcome Measure
TNF-alpha Outcome Measure
Ubiquinone-2 Outcome Measure
Uric acid 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
Ankylosing spondylitis - - Discontinued (III) Australia, Austria, Belgium, Canada, Czech Republic, France, Hungary, Lithuania, Netherlands, Poland, Spain, USA SC / Injection Regeneron Pharmaceuticals, Sanofi 07 Feb 2013
Ankylosing spondylitis - - Discontinued (II) Germany, Turkey SC / Injection Regeneron Pharmaceuticals, Sanofi 07 Feb 2013
COVID 2019 infections - - Phase II/III USA IV / Injection Regeneron Pharmaceuticals 19 Mar 2020
COVID 2019 infections - - Phase II/III Canada, France, Germany, Italy, Japan, Russia, Spain IV / Injection Sanofi 26 Mar 2020
Giant cell arteritis - Combination therapy Phase III Argentina, Australia, Austria, Belgium, Canada, Croatia, Denmark, Estonia, Finland, France, Germany, Hungary, Israel, Italy, Netherlands, Portugal, Russia, Scotland, Slovenia, Spain, Swaziland, Sweden, USA, United Kingdom SC / Injection Regeneron Pharmaceuticals, Sanofi 28 Aug 2018
Juvenile rheumatoid arthritis in patients with polyarticular-course juvenile idiopathic arthritis - Phase II Argentina, Canada, Chile, Czech Republic, Estonia, Finland, France, Germany, Italy, Mexico, Netherlands, Poland, Russia, Spain, USA, United Kingdom SC / Injection Regeneron Pharmaceuticals, Sanofi 01 Sep 2016
Polymyalgia rheumatica - Combination therapy Phase III Argentina, Australia, Belgium, Canada, Estonia, France, Germany, Hungary, Israel, Italy, Japan, Netherlands, Russia, Spain, Switzerland, USA, United Kingdom SC / Injection Regeneron Pharmaceuticals, Sanofi 28 Aug 2018
Rheumatoid arthritis - Monotherapy Marketed Japan SC / Injection Asahi Kasei Pharma Corp, Sanofi, Regeneron Pharmaceuticals 05 Feb 2018
Rheumatoid arthritis - Monotherapy Marketed Canada, France, Germany, Netherlands, United Kingdom SC / Injection Regeneron Pharmaceuticals, Sanofi 07 Feb 2018
Rheumatoid arthritis - Monotherapy, Second-line therapy or greater Marketed USA SC / Injection Regeneron Pharmaceuticals, Sanofi 12 Dec 2017
Rheumatoid arthritis - Adjunctive treatment Marketed Japan SC / Injection Asahi Kasei Pharma Corp, Sanofi, Regeneron Pharmaceuticals 05 Feb 2018
Rheumatoid arthritis In combination with methotrexate or other disease-modifying antirheumatic drugs Combination therapy, Second-line therapy or greater Marketed USA SC / Injection Regeneron Pharmaceuticals, Sanofi 12 Dec 2017
Rheumatoid arthritis - Adjunctive treatment Marketed Canada, France, Germany, Netherlands, United Kingdom SC / Injection Regeneron Pharmaceuticals, Sanofi 07 Feb 2018
Rheumatoid arthritis - Adjunctive treatment Registered European Union, Iceland, Liechtenstein, Norway SC / Injection Regeneron Pharmaceuticals, Sanofi 27 Jun 2017
Rheumatoid arthritis - Monotherapy Registered European Union, Iceland, Liechtenstein, Norway SC / Injection Regeneron Pharmaceuticals, Sanofi 27 Jun 2017
Rheumatoid arthritis - Adjunctive treatment Phase III Argentina, Australia, Belarus, Brazil, Chile, Colombia, Ecuador, Egypt, India, Israel, Malaysia, Mexico, New Zealand, Peru, Philippines, Russia, South Africa, South Korea, Taiwan, Thailand, Turkey SC / Injection Regeneron Pharmaceuticals, Sanofi 22 Aug 2013
Rheumatoid arthritis - Monotherapy Phase III Chile, Israel, Peru, Russia, South Africa, South Korea, Ukraine SC / Injection Regeneron Pharmaceuticals, Sanofi 01 Feb 2015
Rheumatoid arthritis - - No development reported (I) Moldova SC / Injection Regeneron Pharmaceuticals, Sanofi 04 Nov 2017
Uveitis - - Phase II Czech Republic, France, Germany, Italy, Spain, Turkey, USA SC / Injection Regeneron Pharmaceuticals, Sanofi 02 Sep 2013

Commercial Information

Involved Organisations

Organisation Involvement Countries
Regeneron Pharmaceuticals Originator USA
sanofi-aventis Originator France
Regeneron Pharmaceuticals Owner USA
Sanofi Owner France
Asahi Kasei Pharma Corp Market Licensee Japan
Biomedical Advanced Research and Development Authority Funder USA

Brand Names

Brand Name Organisations Indications Countries
Kevzara Regeneron Pharmaceuticals, Asahi Kasei Pharma Corp Rheumatoid arthritis Canada, European Union, Japan, USA

Credit Suisse Market Status

Indication Region Company Phase Expected Launch Year Probability of Success% Patent Expiry Year Expected Generic Entry Last Update
JIA/SJA Wrld (50% US) Regeneron, Sanofi II 2022 20 2029 - 02 Apr 2020
polymyalgia Wrld (50% US) Regeneron, Sanofi III 2023 40 2029 - 02 Apr 2020
Rheumatoid Arthritis ex US Regeneron, Sanofi Marketed 2017 100 2027 - 02 Apr 2020
Rheumatoid Arthritis US Regeneron, Sanofi Marketed 2017 100 2029 - 02 Apr 2020
uveitis Wrld (50% US) - Development Stopped - - - - 02 Apr 2020
Vasculitis Wrld (50% US) Regeneron, Sanofi III 2023 50 2029 - 02 Apr 2020

Credit Suisse Financial Forecast

Indication Region 2016 2017 2018 2019 2020 2021 2022 2023 2024 2025 Last Update
JIA/SJA Wrld (50% US) 0 0 0 0 0 0 20 50 75 100 02 Apr 2020
polymyalgia Wrld (50% US) 0 0 0 0 0 0 0 20 50 75 02 Apr 2020
Rheumatoid Arthritis ex US 0 1 22 78 110 140 160 192 211 232 02 Apr 2020
Rheumatoid Arthritis US 0 11 75 129 170 210 240 288 317 348 02 Apr 2020
Vasculitis Wrld (50% US) 0 0 0 0 0 0 0 50 100 200 02 Apr 2020
Total 0 12 97 207 280 350 420 600 753 955

Scientific Summary

  • Adverse Events Occasional: Elevated liver enzymes; Hypercholesterolaemia; Infections; Neutropenia

Adverse Events

Pooled analysis:

Long-term five year safety data from six clinical trials showed that the incidence rate of adverse events of special interest (AESIs) was generally stable, without any signal for increased rate of any AESI (including serious AEs and serious infection) over time. There was a decline over time in the incidences of injection site reaction, ANC <1 Giga/L and elevated ALT [29] .

Rheumatoid arthritis

Phase

III: Sarilumab at the doses of 200mg, 150mg and placebo led to infections in 30%, 22% and 27% of subjects and injection site reactions in 8%, 7% and 1% of subjects, in the SARIL-RA-TARGET phase III trial. Serious adverse events were observed in 5%, 3% and 3% of subjects treated with sarilumab 200mg, sarilumab 150mg and placebo, respectively. The most common laboratory abnormality was found to be reduction in neutrophil count without any other unexpected safety findings. Serious infections were reported in 2, 1 and 2 patients in the sarilumab 200mg, 150mg and placebo group, respectively. The most frequent events leading to treatment discontinuation were infection and neutropenia. Incidence of treatment-emergent adverse events was 65% and 66% among patients treated with 200mg and 150mg of sarilumab, respectively, versus 50% in the placebo arm [39] [40] [38] .
[41]

According to updated results from 320 patients in the open label extension (OLE) portion of a monotherapy phase III SARIL-RA-MONARCH study, at week 24, treatment-emergent adverse events (TEAEs) were observed in 76.1% versus 70.9% patients, serious TEAEs were seen in 11% versus 3.6% patients, infections were observed in 41.9% versus 35.8% patients, and serious infections were seen in 1.9% versus 0% patients in the switch and continuation groups, respectively, wherein two deaths also occurred in the switch group (one each due to malignancy and cerebrovascular accident), and one death (due to subarachnoid haemorrhage) was seen in the continuation group. Ulcerations, perforations, diverticulitis or other GI-related adverse events were not seen in the groups. Discontinuations due to TEAEs occurred in 5.8% of patients in the switch group and 3.6% in the continuation group. Earlier results from the trial showed that adverse events (64% for both sarilumab and adalimumab groups), serious adverse events (5% for sarilumab vs 7% for adalimumab), infections (29% for sarilumab vs 28% for adalimumab) and serious infections (1% for both groups) were generally similar between groups. The most frequent events were neutropenia (14% sarilumab vs 1% adalimumab) and injection site erythema (8% sarilumab vs 3% adalimumab); headache and worsening of rheumatoid arthritis were more common with adalimumab. Neutropenia was not associated with an increased incidence of infections. Most injection site reactions were mild; only two cases led to treatment discontinuation in the sarilumab arm. One death was reported in the sarilumab arm, 35 days after initiating treatment, due to acute cardiac failure. In the open-label extension study adverse events reported were infections, leukopenia, thrombocytopenia, hepatic disorders, GI ulcerations/diverticulitis/potential GI perforation, elevation in lipis, hypersentivity, injection-site reactions, malignancy, lupus-like syndrome and demyelinating disorders. Two deaths occurred in the switch group (malignancy; cerebrovascular accident) versus one in the continuation group (subarachnoid hemorrhage). No GI-related AEs (ulcerations/perforations/diverticulitis) were observed [47] [48] [52] [50] [53] .

In a phase III, long-term follow-up EXTEND trial, the most common reasons for dose reduction were decreased ANC (11.3%; n=187) and increased ALT (3.9%; n=65) levels. The most common non-laboratory reason for dose reduction was infection (0.4%; n=7). At the time of analysis, 76.9% of patients (n=247) whose dose was reduced were continuing treatment, with a median treatment duration of 2.3 years after dose reduction. Improvements in ANC and ALT levels were observed over the 6 months after dose reduction [55] [54] .

In a phase III, long-term follow-up EXTEND trial, treatment-emergent adverse events (TEAEs) occurred in 89.7% of patients over 3 years. The most common TEAEs (≥10%) were neutropenia (19.4%), increased alanine aminotransferase (13.0%), and upper respiratory tract infections (12.7%). Infections were the most frequently reported serious AE (4.2/100 patient-years). The most common reasons for dose reduction were decreased ANC (11.3%; n 187) and increased ALT (3.9%; n = 65) levels. The most common non-laboratory reason for dose reduction was infection (0.4%; n=7). At the time of analysis, 76.9% of patients (n = 247) whose dose was reduced were continuing treatment, with a median treatment duration of 2.3 years after dose reduction. Improvements in ANC and ALT levels were observed over the 6 months after dose reduction. Of the 1 197 randomized patients in MOBILITY trial, 901 participated in EXTEND trial; at year 3, all patients received open-label sarilumab for 2 years [55] [93] [54] .

In the MOBILITY and TARGET trials, the most common adverse reactions (occurring in at least 3% of patients) were neutropenia (7-10% vs. 0.2%), increased alanine aminotransferase (5% vs. 2%), injection site erythema (4-5% vs. 0.9%), upper respiratory infections (3-4% vs. 2%) and urinary tract infections (3% vs. 2%) [12] [41] [31] .

Phase IIb/III

Results for the phase III portion of the SARIL-RA-MOBILITY trial (n = 1197) showed a higher occurrence of treatment emergent adverse events leading to withdrawal in the sarilumab groups compared to placebo; 13.9%, 12.5% and 4.7% of patients withdrew in the sarilumab 200mg, sarilumab 150mg and placebo groups, respectively. Infections occurred in 39.6%, 40.1% and 31.1% of patients in the 200mg, 150mg and placebo groups, respectively. Serious infections occurred in 4.0%, 2.6% and 2.3% of patients in these groups, respectively. Sarilumab treatment was associated with a dose-dependent decrease in mean neutrophil counts, but serious infections were not associated with grades 3/4 neutropenia. Sarilumab treatment was associated with elevated transaminases and increases in mean LDL cholesterol [33] . In the phase IIb portion of the randomised, placebo controlled, trial in patients with rheumatoid arthritis (n=306), infections (non-serious), neutropenia, and liver function test abnormalities were reported more frequently in the sarilumab + methotrexate treatment groups compared with methotrexate alone. The incidence of serious adverse events among the five sarilumab + methotrexate treatment groups and methotrexate alone treatment group were similar [35] .

Phase I

sarilumab was generally well tolerated according to pooled data from three phase I studies involving patients with rheumatoid arthritis (RA). The most commonly reported adverse events were upper respiratory infections, increases in ALT levels and RA flare. One serious adverse event was reported (RA flare) that required hospitalisation [92] .

Ankylosing spondylitis

In the phase IIb ALIGN trial in patients with ankylosing spondylitis (n=300) who had inadequate response to NSAIDS, treatment with sarilumab in combination with methotrexate was well tolerated. However, infections and neutropenia were more common in the sarilumab treatment groups [35] .

Juvenile rheumatoid arthritis:

Phase II:

Results from an open-label phase II trial for sarilumab in children and adolescents with polyarticular juvenile idiopathic arthritis showed that 85.7% patients (comparable across dose and weight groups) reported treatment emergent adverse event which included infections (66.7%). 12 patients reported grade 3/4 neutropenia, mostly in dose 3 (n=6) and in Group B (n=8). None was associated with infection and all was resolved in a few days. Overall, four patients discontinued due to neutropenia and one due to alanine aminotransferase increase. There were no serious adverse events, no cases of gastrointestinal perforation and no deaths [79] [78] .

COVID-2019 Infections: Results from the phase II/III study showed no new safety findings were observed for sarilumab use in COVID-19 patients [74] [72] .

Pharmacodynamics

Summary

In the RA-MOBILITY study, sarilumab significantly reduced biomarkers of bone resorption and joint damage in patients with rheumatoid arthritis. Treatment with sarilumab also decreased markers of tissue destruction and synovial inflammation relative to placebo at week 2, with greater reductions observed at week 24. Significant reductions in chemokine (CXC motif) ligand 13 (marker of lymphoid RA synovial phenotype) and MMP 3 (synovial inflammation marker) were observed in ACR 50 responders relative to non-responders in the sarilumab 150mg q2w group at week 24. Additionally, ACR 50 responders demonstrated greater post-treatment reductions in collagen type I MMP-cleaved fragment and C-reactive protein compared with ACR 50 non-responders. Results were reported from 384 patients enrolled in a randomised study [37] [31] .

Sarilumab (50 - 200mg, SC) inhibited IL-6Rα in patients with rheumatoid arthritis according to pooled data from three phase I trials. Inhibition of IL-6Rα caused dose-dependent reductions in hsCRP, SAA, ESR and serum hepcidin and increases in IL-6 [92] .

In the phase III ASCERTAIN trial, sarilumab SC 200 mg q2w (once every 2 weeks) achieved >90% receptor occupancy (RO) after the first dose, which maintained over the dosing interval throughout the 24-week treatment course; at the lower dose of 150 mg q2w, RO was >90% from the second dose onwards. RO for tocilizumab SC, at 162 mg q2w, was >90% immediately after the first dose but dropped below 50% prior to the second dose and for tocilizumab IV at 4 mg/kg q4w (once every 4 weeks), the RO was high immediately after the first dose (>99% at Week 1) but decreased over the dosing interval. At trough steady-state (Week 24), RO was greater with sarilumab SC 200 mg q2w (98%) and 150 mg q2w (94%) compared with tocilizumab SC 162 mg q2w (84%) and IV 4 mg/kg q4w (60%). The higher doses of tocilizumab SC 162 mg qw (once every week) and tocilizumab IV 8 mg/kg q4w were able to maintain RO ≥99% at steady state, similar to sarilumab SC 200 mg at steady state. The greatest suppression in C-Reactive Protein (CRP) level was seen in patients who received sarilumab SC (at either dose) or the higher IV tocilizumab dose and proportionally smaller reductions in CRP levels were observed with the lower IV tocilizumab dose (4 mg/kg q4w), consistent with the lower RO of tocilizumab [44] [43] .

Therapeutic Trials

Juvenile rheumatoid arthritis:

Phase II:

Results from an open-label phase II trial for sarilumab in children and adolescents with polyarticular juvenile idiopathic arthritis showed all patients attained ACR30. ACR70 was achieved by 50%, 62%, and 100% patients with doses 1, 2, and 3, respectively. JADAS27-CRP mean % change from baseline in doses 1, 2, and 3 were -74.6%, -73.1%, and -87.9%, respectively [79] [78] .

Pooled analysis:

Long-term five year results from six clinical trials showed that initial treatment with either dose of sarilumab (150mg or 200mg) resulted in significantly better radiographic outcome than placebo. Initial treatment with sarilumab 200mg portended better radiographic outcome than 150mg or placebo. Mean duration of sarilumab treatment in the safety population was 2.6 years (maximum 6.8), which represent a total of 7412 cumulative patient-years of exposure [29] .

Rheumatoid arthritis

According to updated results from 320 patients in the open label extension (OLE) portion of the phase III SARIL-RA-MONARCH study, at week 24, the mean change from baseline DAS28-ESR was -2.28 and -3.36 in the switch and continuation groups respectively, while at week 48, these values were -4.06 and -4.18 for the two groups, respectively. By week 48 of the OLE, the proportion of patients in the switch and continuation groups who achieved DAS28-ESR ≤3.2 was 61.3% versus 61.2%, while the proportion of patients who achieved DAS28-ESR <2.6 was 43.9% and 49.7%, respectively. For the same groups, the proportion of patients achieving DAS28-CRP<2.6 was 52.9% vs 52.1%, respectively. CDAI remission was 12.3% and 18.8% (p=0.1054). Mean improvement in HAQ-DI was seen from 1.21 to 0.91 in the switch group, but the same level of improvement was not witnessed in continuation group (1.01 to 0.84). Earlier results showed that sarilumab, when administered subcutaneously (200mg every 2 weeks) was superior over adalimumab monotherapy (40 mg every 2 weeks) in improving signs and symptoms of rheumatoid arthritis and physical function at 24 weeks. At week 24, significantly greater decrease in DAS28-ESR scores, greater incidence of DAS28-ESR remission and ACR20/50/70 responses and improvement in HAQ–Disability Index were observed with sarilumab versus adalimumab. Specifically, a statistically significant difference from baseline in DAS28-ESR was shown in favour of sarilumab (-3.28 for sarilumab compared to -2.22 for adalimumab, p < 0.0001). As measured by the American College of Rheumatology score of 20 percent improvement (ACR20), 72% and 58% improvement was observed (p < 0.01). ACR50 was achieved by 45% of patients in sarilumab as compared to 29% patients who achieved ACR50 in adalimumab arm with p-value = 0.0017. Additionally, ACR70 was achieved by 23% patients in sarilumab arm and 11% patients in adalimumab arm with p-value = 0.0036. In sarilumab treatment arm rate of DAS28-SR remission (score<2.6) was 26% when compared to 7% in adalimumab with p-value < 0.0001. Improvement was observed in HAQ-DI at week-24 as change from baseline in sarilumab was -0.61 and -0.43 for adalimumab, with p-value = 0.0037. A greater numerical response was observed in clinical disease activity index (CDAI) defined by change in baseline at week-24 was -28.9 in sarilumab treatment arm compared to -25.2 in adalimumab-arm. CDAI remission rates were found to be higher in sarilumab arm (7%) as compared to adalimumab (2%) (p < 0.05). High improvement was observed in disability, pain and fatigue adult in patients treated with sarilumab as compared to patients in adalimumab. The improvements included patient-reported outcomes, which were measured by Medical Outcomes Short Form 36 Health Survey, physician component summary score (PCS), mental component summary score (MCS) and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F). The data was reported from the randomised, double-blind SARIL-RA-MONARCH conducted in 369 patients. In the open-label extension study, 369 patients enrolled in the trial and DAS28-ESR and CDAI endpoints, >40% of switch patients achieved a minimally important difference (MID) improvement from baseline by week 12, increasing to >50% by week 48. Response rates were higher in sarilumab-treated than adalimumab-treated patients, hence fewer patients in the continuation group achieved additional MID during extension study [47] [48] [49] [50] [51] [52] [53] .

The co-primary endpoints of the phase III SARIL-RA-TARGET trial were met demonstrating statistically significant improvement in signs and symptoms of rheumatoid arthritis at 24 weeks and physical function at 12 weeks on treatment with sarilumab, in comparison with placebo (p < 0.001). As measured by the American College of Rheumatology score of 20 percent improvement (ACR20), 61% and 56% improvement was observed in 200mg and 150mg treatment group in comparison with 34% of improvement observed with placebo, all in combination with DMARD therapy. At week 12, improvement in physical function, as assessed by the change from baseline in the Health Assessment Question-Disability Index (HAQ-DI), was -0.49, -0.50 and -0.29 in the sarilumab 200mg (p=0.0004), sarilumab 150mg (p=0.0007) and placebo groups, respectively. The trial also met its secondary endpoints of ACR50, ACR70, disease activity score/index, and HAQ-DI at 24 weeks. Sarilumab efficacy was maintained in TARGET patients 24 weeks after dose reduction as assessed by ACR20 response rates (83.1% and 85.1%, respectively) and improvements in HAQ–Disability Index scores (-0.68 and -0.82, respectively) [55] [40] [38] [41] .

The three co-primary endpoints of the phase III part of the SARIL-RA-MOBILITY trial were met, demonstrating significant improvements in signs and symptoms of disease at 24 weeks, in physical function at 16 weeks and inhibition of joint damage progression at 52 weeks, for sarilumab versus placebo (all p < 0.0001). In the phase III part of the phase II/III trial (n = 1197), at 24 weeks, the proportion of patients achieving ACR20 was 66%, 58% and 33% in the 200mg, 150mg and placebo groups, respectively; at 16 weeks, the sarilumab groups achieved significant improvement in physical function, as measured by the Health Assessment Question-Disability questionnaire (sarilumab 200mg, -0.58; sarilumab 150mg, -0.54; placebo, -0.30) [12] . At week 52, the inhibition of progression of structural damage, as measured by the modified Van der Heijde total Sharp score, was significantly improved in the sarilumab groups: 0.25, 0.90, and 2.78 in the 200mg, 150mg and placebo groups, respectively; at week 52, the 200mg dose group achieved a reduction of ~90% in radiographic progression, compared with placebo. Sarilumab also showed significant improvements in other ACR measures at week 24 (p < 0.0001 vs placebo); in the 200mg, 150mg and placebo groups, 46%, 37% and 17% of patients, respectively, achieved ACR50. ACR70 was achieved by 25%, 20% and 7% of patients, respectively. Sarilumab efficacy was maintained in MOBILITY patients 24 weeks after dose reduction as assessed by ACR20 response rates (83.1% and 85.1%, respectively) and improvements in HAQ–Disability Index scores (-0.68 and -0.82, respectively) [55] [32] [33] [31] .

Earlier data from the phase IIb portion of the randomised, placebo controlled SARIL-RA-MOBILITY trial patients with rheumatoid arthritis (n=306) demonstrated that treatment with sarilumab in combination with methotrexate significantly improved signs and symptoms of moderate-to-severe disease compared with methotrexate alone. Response was dose-dependent. The proportion of patients achieving at least a 20% improvement in symptoms (ACR20) after 12 weeks was 49% of those who received the lowest sarilumab dose (150mg) and 72% of those who received the highest dose regimen (200mg), compared with 46.2% of patients who received methotrexate. Sarilumab also demonstrated benefit compared with placebo in other clinical activity measures, including ACR50, ACR70, and Disease Activity Score 28 scores [35] .

In a phase III, long-term follow-up EXTEND trial, percentages of patients achieving DAS28-CRP <2.6 or CDAI ≤2.8 were similar in patients originally treated with either dose of sarilumab or placebo, though the initial sarilumab 200 mg group exhibited the most favourable outcomes. Improvements were maintained within each group from year 2 to year 3. Three-year radiographic data were available for 755 patients; linear extrapolation was used in 29. Modified total Sharp scores at year 3 in the initial placebo and sarilumab 150 and 200 mg groups were only slightly increased since year 2. Of the 1197 randomized patients in MOBILITY trial, 901 participated in EXTEND trial; at year 3, all patients received open-label sarilumab for 2 years [93] [54] .

Ankylosing spondylitis

In the phase IIb ALIGN trial in patients with ankylosing spondylitis (n=300) who had inadequate response to NSAIDS, treatment with sarilumab in combination with methotrexate did not improve signs and symptoms of active disease compared with methotrexate alone. The trial did therefore not meet its primary endpoint [35] [83] .

COVID-2019 infections: Preliminary results from the phase II portion of the phase II/III trial showed that primary end point of the trial was met as indicated by rapidly lowered C-reactive protein in sarilumab treated patients. Baseline levels of IL-6 were elevated across all treatment arms, with higher levels observed in "critical" patients compared to "severe" patients. Explorarory analysis results showed that no notable benefit on clinical outcomes when combining the "severe" and "critical" groups, versus placebo was observed in sarilumab treated patients. However, negative trends for most outcomes in the "severe" group, while positive trends for all outcomes in the "critical" group were observed. Review of the discontinued "severe" group data revealed that the negative trends in the phase II trial (n=126) were not reproduced in phase III trial (n=276), and that clinical outcomes were balanced across the sarilumab and placebo treatment arms. Outcomes for the "severe" group were better than expected based on prior reports, regardless of treatment assignment as evident from example that in the phase II portion, approximately 80% were discharged, 10% of patients died and 10% remain hospitalized in the severe group [74] [72] .

Future Events

Expected Date Event Type Description Updated
31 Dec 2023 Regulatory Status Sanofi and Regenerone announces intention to submit a regulatory application for Juvenile rheumatoid arthritis (systemic) in 2023 or later [76] 13 Feb 2020
31 Dec 2022 Regulatory Status Sanofi announces intention to regulatory application for Giant cell arteritis and Polymyalgia rheumatic in 2022 [86] 14 Feb 2019
31 Dec 2020 Trial Update Regeneron Pharmaceuticals plans a phase II/III trial for COVID-2019 infections in USA (SC, Injection) (9287715) (700319835) [71] 24 Mar 2020
31 Mar 2020 Company Name Changes Sanofi and Regeneron Pharmaceuticals intend to make changes in their antibody agreement for sarilumab by first quarter of 2020 [8] 16 Dec 2019
01 Jan 2020 Regulatory Status Sanofi announces intention to submit regulatory application Juvenile rheumatoid arthritis in USA and EU in 2020 [88] 03 Aug 2018
31 Dec 2019 Trial Update Regeneron Pharmaceuticals plans clinical trials for Rheumatoid arthritis in 2019 [87] 26 Oct 2018
31 Dec 2018 Trial Update Regeneron plans a phase II trial for Juvenile rheumatoid arthritis(systemic) in 2018 [89] 19 Dec 2017
17 Sep 2018 Trial Update Regeneron plans a phase III trial for Giant cell arteritis in September 2018 (NCT03600805) (EudraCT2017-002988-18) (700291356) [89] 11 Oct 2018
17 Sep 2018 Trial Update Regeneron plans a phase III trial for Polymyalgia rheumatica in September 2018 (NCT03600818) (EudraCT2017-002989-42) (700291357) [89] 11 Oct 2018
31 Dec 2017 Regulatory Status Regeneron Pharmaceuticals announces intention to apply for regulatory approvals outside USA in 2017 [90] 08 Aug 2017
22 May 2017 Regulatory Status PDUFA action date extended by US FDA to 22/05/2017 for NDA for Rheumatoid arthritis [91] 08 Aug 2017

Development History

Event Date Update Type Comment
27 Apr 2020 Scientific Update Efficacy and adverse events data from a phase-II/III clinical trials in COVID-2019 infections released by Regeneron Pharmaceuticals and Sanofi [74] Updated 29 Apr 2020
15 Apr 2020 Trial Update Sanofi and Regenerone suspend a phase III trials in Polymyalgia rheumatica (Combination therapy) in Argentina, Australia, Belgium, Canada, Canada, Estonia, France, Germany, Hungary, Israel, Italy, Japan, Switzerland, Spain, United Kingdom, Russia, Netherlands (SC) (NCT03600818) (EudraCT2017-002989-42) Updated 23 Apr 2020
02 Apr 2020 Financial Update Credit Suisse financial data update Updated 11 Apr 2020
26 Mar 2020 Phase Change - II/III Phase-II/III clinical trials in COVID-2019 infections in Germany, France, Italy, Spain, Russia, Canada (IV) (EudraCT2020-001162-12) Updated 01 Apr 2020
26 Mar 2020 Phase Change - II/III Phase-II/III clinical trials in COVID-2019 infections in Japan (IV) (EudraCT2020-001162-12) Updated 01 Apr 2020
23 Mar 2020 Trial Update Sanofi plans a phase II trial for COVID-2019 infections in Italy Updated 23 Mar 2020
21 Mar 2020 Company Involvement Regeneron Pharmaceuticals receives Biomedical Advance Research and Development Authority (BARDA) grant from US Department of Health and Human Services for the development of sarilumab for COVID-2019 infections [2] Updated 30 Mar 2020
19 Mar 2020 Phase Change - II/III Phase-II/III clinical trials in COVID-2019 infections in USA (IV) [70] (NCT04315298) Updated 23 Mar 2020
16 Mar 2020 Trial Update Regeneron Pharmaceuticals plans a phase II/III trial for COVID-2019 infections in USA (SC, Injection) [71] [71] Updated 24 Mar 2020
06 Feb 2020 Regulatory Status Sanofi and Regenerone announces intention to submit a regulatory application for Juvenile rheumatoid arthritis (systemic) in 2023 or later [76] Updated 13 Feb 2020
10 Dec 2019 Company Involvement Sanofi and Regeneron Pharmaceuticals intend to make changes in their antibody agreement for sarilumab by first quarter of 2020 [8] Updated 16 Dec 2019
10 Dec 2019 Licensing Status Sanofi and Regeneron Pharmaceuticals propose to make changes in the antibody agreement [8] Updated 16 Dec 2019
12 Jun 2019 Scientific Update Efficacy and adverse events data from the phase III open-lable extension MONARCH trial in Rheumatoid arthritis presented at the 20th Annual Congress of the European League Against Rheumatism (EULAR-2019) [47] Updated 21 Jun 2019
12 Jun 2019 Scientific Update Pharmacodynamics data from the phase III ASCERTAIN study in Rheumatoid arthritis presented at the 20th Annual Congress of the European League Against Rheumatism (EULAR-2019) [44] Updated 21 Jun 2019
12 Jun 2019 Scientific Update Efficacy and adverse events data from a phase II trial in Juvenile rheumatoid arthritis presented at the 20th Annual Congress of the European League Against Rheumatism (ELAR-2019) [79] Updated 20 Jun 2019
07 Feb 2019 Regulatory Status Sanofi announces intention to regulatory application for Giant cell arteritis and Polymyalgia rheumatic in 2022 [86] Updated 14 Feb 2019
19 Oct 2018 Trial Update Regeneron Pharmaceuticals plans clinical trials for Rheumatoid arthritis in 2019 [87] Updated 26 Oct 2018
28 Aug 2018 Phase Change - III Phase-III clinical trials in Giant cell arteritis (Combination therapy) in United Kingdom, Swaziland, Swaziland, Sweden, Spain, Slovenia, Scotland, Russia, Portugal, Netherlands, Italy, Israel, Hungary, Germany, France, Finland, Estonia, Denmark, Croatia, Canada, Belgium, Australia, Austria, Argentina (SC) (NCT03600805) (EudraCT2017-002988-18) Updated 28 Apr 2020
28 Aug 2018 Phase Change - III Phase-III clinical trials in Polymyalgia rheumatica (Combination therapy) in Argentina, Australia, Belgium, Canada, Canada, Estonia, France, Germany, Hungary, Israel, Italy, Japan, Switzerland, Spain, United Kingdom, Russia, Netherlands (SC) (NCT03600818) (EudraCT2017-002989-42) Updated 23 Apr 2020
28 Aug 2018 Phase Change - III Phase-III clinical trials in Giant cell arteritis (Combination therapy) in USA (SC) (NCT03600805) Updated 11 Oct 2018
28 Aug 2018 Phase Change - III Phase-III clinical trials in Polymyalgia rheumatica (Combination therapy) in USA (SC) (NCT03600818) Updated 11 Oct 2018
28 Aug 2018 Trial Update Regeneron resumes recruitment in phase II trial for Juvenile rheumatoid arthritis (NCT02991469) Updated 29 Aug 2018
31 Jul 2018 Regulatory Status Sanofi announces intention to submit regulatory application Juvenile rheumatoid arthritis in USA and EU in 2020 [88] Updated 03 Aug 2018
24 Jun 2018 Biomarker Update Biomarkers information updated Updated 31 Aug 2018
13 Jun 2018 Scientific Update Long-term efficacy and adverse events data from six clinical trials in Rheumatoid arthritis presented at the 19th Annual Congress of the European League Against Rheumatism (EULAR-2018) [29] Updated 10 Jul 2018
13 Jun 2018 Scientific Update Updated efficacy and adverse events data from the phase III SARIL-RA-MONARCH trial in Rheumatoid arthritis presented at the 19th Annual Congress of the European League Against Rheumatism (EULAR-2018) [48] Updated 10 Jul 2018
08 Feb 2018 Patent Information Regeneron Pharmaceuticals has patent protection for Sarilumab in USA and European Union [85] Updated 20 Apr 2018
07 Feb 2018 Phase Change - Marketed Launched for Rheumatoid arthritis (Adjunctive treatment) in Netherlands, United Kingdom, Germany (SC) in second half of 2017 Updated 09 Feb 2018
07 Feb 2018 Phase Change - Marketed Launched for Rheumatoid arthritis (Monotherapy) in United Kingdom, Netherlands and Germany (SC) in second half of 2017 Updated 09 Feb 2018
05 Feb 2018 Phase Change - Marketed Launched for Rheumatoid arthritis (Adjunctive treatment) in Japan (SC) [11] Updated 14 May 2018
05 Feb 2018 Phase Change - Marketed Launched for Rheumatoid arthritis (Monotherapy) in Japan (SC) [11] Updated 14 May 2018
25 Jan 2018 Phase Change - Marketed Launched for Rheumatoid arthritis (Adjunctive treatment) in France (SC), before January 2018 (NCT03449758) Updated 08 Mar 2018
25 Jan 2018 Phase Change - Marketed Launched for Rheumatoid arthritis (Monotherapy) in France (SC), before January 2018 (NCT03449758) Updated 08 Mar 2018
13 Dec 2017 Trial Update Regeneron plans a phase III trial for Giant cell arteritis in September 2018 (NCT03600805) (EudraCT2017-002988-18) [89] Updated 11 Oct 2018
13 Dec 2017 Trial Update Regeneron plans a phase III trial for Polymyalgia rheumatica in September 2018 (NCT03600818) (EudraCT2017-002989-42) [89] Updated 11 Oct 2018
13 Dec 2017 Trial Update Regeneron plans a phase II trial for Juvenile rheumatoid arthritis(systemic) in 2018 [89] Updated 19 Dec 2017
12 Dec 2017 Trial Update Sanofi suspends a phase II trial in Juvenile rheumatoid arthritis (In children, In adolescents, In infants) in Spain, Estonia, France, Russia, Finland, Italy, the Netherlands, the UK, Germany, Czech Republic, Chile, Canada, Argentina, Poland and the US as they have decided to amend the current protocol (NCT02991469) Updated 20 Dec 2017
12 Dec 2017 Licensing Status Sanofi and Asahi Kasei Pharma agree to co-promote sarilumab in Japan for Rheumatoid arthritis [10] Updated 15 Dec 2017
12 Dec 2017 Phase Change - Marketed Launched for Rheumatoid arthritis (Combination therapy, Second-line therapy or greater) in USA (SC), before December 2017 [10] Updated 15 Dec 2017
12 Dec 2017 Phase Change - Marketed Launched for Rheumatoid arthritis (Monotherapy, Second-line therapy or greater) in USA (SC), before December 2017 [10] Updated 15 Dec 2017
08 Nov 2017 Phase Change - Registered Registered for Rheumatoid arthritis (Adjunctive treatment) in Japan before November 2017 (SC) [24] Updated 16 Nov 2017
08 Nov 2017 Phase Change - Registered Registered for Rheumatoid arthritis (Monotherapy) in Japan before November 2017 (SC) [24] Updated 16 Nov 2017
04 Nov 2017 Phase Change - No development reported No recent reports of development identified for phase-I development in Rheumatoid-arthritis in Moldova (SC, Injection) Updated 04 Nov 2017
03 Nov 2017 Scientific Update Updated adverse events and efficacy data from the phase III SARIL-RA-MONARCH trial in Rheumatoid arthritis presented at the 81st American College of Rheumatology and the 52nd Association of Rheumatology Health Professionals Annual Scientific Meeting (ACR/ARHP-2017) [49] Updated 28 Dec 2017
03 Aug 2017 Regulatory Status Regeneron Pharmaceuticals announces intention to apply for regulatory approvals outside USA in 2017 [90] Updated 08 Aug 2017
27 Jun 2017 Phase Change - Registered Registered for Rheumatoid arthritis (Adjunctive treatment) in Iceland, Norway and Liechtenstein (SC) [20] Updated 09 Feb 2018
27 Jun 2017 Phase Change - Registered Registered for Rheumatoid arthritis (Monotherapy) in Iceland, Norway and Liechtenstein (SC) [20] Updated 09 Feb 2018
27 Jun 2017 Phase Change - Registered Registered for Rheumatoid arthritis (Adjunctive treatment) in European Union (SC) [20] Updated 30 Jun 2017
27 Jun 2017 Phase Change - Registered Registered for Rheumatoid arthritis (Monotherapy) in European Union (SC) [20] Updated 30 Jun 2017
22 May 2017 Phase Change - Registered Registered for Rheumatoid arthritis (Combination therapy, Second-line therapy or greater) in USA (SC) [12] Updated 25 May 2017
22 May 2017 Phase Change - Registered Registered for Rheumatoid arthritis (Monotherapy, Second-line therapy or greater) in USA (SC) [12] Updated 25 May 2017
22 May 2017 Scientific Update Efficacy and adverse event data from the phase III MOBILITY and TARGET trials in Rheumatoid arthritis released by Sanofi and Regeneron [12] Updated 25 May 2017
28 Apr 2017 Regulatory Status PDUFA action date extended by US FDA to 22/05/2017 for NDA for Rheumatoid arthritis [91] Updated 08 Aug 2017
28 Apr 2017 Regulatory Status USFDA accepts the resubmission of the Biologics License Application (BLA) for Rheumatoid arthritis [13] Updated 04 May 2017
21 Apr 2017 Regulatory Status Committee for Medicinal Products for Human Use (CHMP) of the EMA recommends approval of Sarilumab for Rheumatoid arthritis (Adjunctive treatment) and Rheumatoid arthritis (Monotherapy) in European Union [22] Updated 25 Apr 2017
21 Apr 2017 Trial Update Sanofi-aventis recherche & développement initiates a phase II trial for Juvenile rheumatoid arthritis in the Netherlands before April 2017 (SC) (EudraCT2015-004000-35) Updated 25 Apr 2017
08 Feb 2017 Phase Change - Marketed Launched for Rheumatoid arthritis (Adjunctive treatment) in Canada (SC) (9212188; 3230222) Updated 01 Mar 2017
08 Feb 2017 Phase Change - Marketed Launched for Rheumatoid arthritis (Monotherapy) in Canada (SC) (9212188; 3230222) Updated 01 Mar 2017
01 Feb 2017 Regulatory Status Regeneron Pharmaceuticals and Sanofi announce intention to resubmit BLA to US FDA in Q1 2017 [14] Updated 06 Feb 2017
12 Jan 2017 Phase Change - Registered Registered for Rheumatoid arthritis (Adjunctive treatment) in Canada (SC) - First global approval (3230220; 9210952) Updated 08 Feb 2017
12 Jan 2017 Phase Change - Registered Registered for Rheumatoid arthritis (Monotherapy) in Canada (SC) - First global approval (3230220; 9210952) Updated 03 Feb 2017
16 Nov 2016 Scientific Update Efficacy data from the phase III SARIL-RA-MONARCH trial in Rheumatoid arthritis (Monotherapy) released by Regeneron Pharmaceuticals [51] Updated 23 Nov 2016
11 Nov 2016 Scientific Update Pharmacodynamics data from the RA-MOBILITY phase II/III trial in Rheumatoid Arthritis presented at the 80th American College of Rheumatology (ARH-2016) and at the 51st Annual Meeting of the Association of Rheumatology and Health Professionals (ARHP-2016) [37] Updated 24 Feb 2017
11 Nov 2016 Scientific Update Updated adverse events and efficacy data from the phase III SARIL-RA-MONARCH trial in Rheumatoid arthritis (Monotherapy) presented at 80th American College of Rheumatology and the 51st Annual Meeting of the Association of Rheumatology and Health Professionals (ACR/ARHP - 2016) [50] Updated 21 Feb 2017
11 Nov 2016 Scientific Update Adverse events and efficacy data from the phase III long-term follow-up EXTEND trial in Rheumatoid arthritis presented at 80th American College of Rheumatology and the 51st Annual Meeting of the Association of Rheumatology and Health Professionals (3221409; 3221506) Updated 20 Feb 2017
10 Nov 2016 Trial Update Sanofi-aventis recherche & développement initiates a phase II trial for Juvenile rheumatoid arthritis in Spain (SC) (EudraCT2015-004000-35) Updated 17 Nov 2016
01 Nov 2016 Trial Update Sanofi completes the SARIL-RA-HARUKA trial in Rheumatoid arthritis (Adjunctive therapy) in Japan (NCT02373202) Updated 19 Dec 2016
31 Oct 2016 Phase Change - Preregistration Preregistration for Rheumatoid arthritis (Monotherapy) in Japan (SC) Updated 09 Feb 2017
31 Oct 2016 Phase Change - Preregistration Preregistration for Rheumatoid arthritis (Adjunctive therapy) in Japan (SC) Updated 09 Nov 2016
28 Oct 2016 Regulatory Status Sanofi receives complete response letter from the FDA for sarilumab in Rheumatoid arthritis [16] Updated 03 Nov 2016
01 Oct 2016 Trial Update Sanofi in collaboration with Regeneron completes a phase-III clinical trial for Rheumatoid arthritis in Japan (NCT02293902) (SC) Updated 14 Dec 2016
01 Sep 2016 Phase Change - II Phase-II clinical trials in Juvenile rheumatoid arthritis (In children, In adolescents, In infants) in France after September 2016 (SC) (NCT02991469) Updated 05 May 2017
01 Sep 2016 Trial Update Sanofi-aventis initiates a phase II trial for Juvenile rheumatoid arthritis (In children, In adolescents, In infants) in United Kingdom and Russia after September 2016 (EudraCT2015-004000-35; NCT02991469) Updated 05 May 2017
01 Sep 2016 Trial Update Sanofi-aventis recherche & développement initiates a phase II trial for Juvenile rheumatoid arthritis (In children, In adolescents, In infants) in Estonia, Finland, Italy and Poland (SC) (NCT02991469) Updated 18 Jan 2017
01 Aug 2016 Phase Change - Preregistration Preregistration for Rheumatoid arthritis (Adjunctive treatment) in European Union (SC) Updated 08 Feb 2017
01 Aug 2016 Phase Change - Preregistration Preregistration for Rheumatoid arthritis (Monotherapy) in European Union (SC) [23] Updated 11 Aug 2016
01 Jun 2016 Phase Change - II Phase-II clinical trials in Juvenile rheumatoid arthritis in Canada, Argentina, USA, Germany (SC) (EudraCT2015-003999-79) (NCT02776735) after June 2016 Updated 14 Sep 2018
01 Jun 2016 Trial Update Sanofi initiates a phase II trial in Juvenile rheumatoid arthritis in France (SC) (NCT02776735) after June 2016 Updated 14 Sep 2018
01 Jun 2016 Phase Change - II Phase-II clinical trials in Juvenile rheumatoid arthritis in United Kingdom, Russia, Poland, Netherlands, Mexico, Italy, Finland, Estonia, Czech Republic, Chile (SC) after June 2016 (NCT02776735) Updated 03 Nov 2016
01 Jun 2016 Phase Change - II Phase-II clinical trials in Juvenile rheumatoid arthritis in Spain (SC) (NCT02776735) Updated 23 Jun 2016
08 Apr 2016 Trial Update Sanofi plans a phase II trial for Juvenile rheumatoid arthritis in Argentina, Canada, Chile, Czech Republic, Estonia, Finland, France, Germany, Italy, Mexico, Netherlands, Poland, Russia, Spain, UK and USA (EudraCT2015-003999-79) Updated 12 Apr 2016
01 Apr 2016 Trial Update Sanofi completes the SARILNIUSATURN trial in Uveitis in USA, Czech Republic, Germany, France, Italy, Spain and Turkey (NCT01900431) Updated 13 May 2016
11 Mar 2016 Regulatory Status Regeneron and Sanofi announces intention to submit regulatory submission to EU in Q3 2016 [52] Updated 16 Mar 2016
11 Mar 2016 Scientific Update Top-line efficacy and adverse event data from a phase III SARIL-RA-MONARCH trial in Rheumatoid arthritis released by Regeneron and Sanofi [52] Updated 16 Mar 2016
01 Mar 2016 Trial Update Regeneron and Sanofi complete a phase I drug interaction trial for Rheumatoid arthritis in USA, Moldova and South Korea (NCT02017639) Updated 21 Apr 2016
01 Mar 2016 Trial Update Sanofi & Regeneron complete the phase III SARIL-RA-EASY trial for Rheumatoid arthritis in USA, Chile, Mexico, Poland, Russia and South Africa (NCT02057250) Updated 21 Apr 2016
01 Mar 2016 Trial Update Sanofi completes a phase I trial for Rheumatoid arthritis in Japan (NCT02404558) Updated 07 Apr 2016
31 Jan 2016 Phase Change - Preregistration Preregistration for Rheumatoid arthritis (Adjunctive treatment) in Canada (SC) Updated 08 Feb 2017
31 Jan 2016 Phase Change - Preregistration Preregistration for Rheumatoid arthritis (Monotherapy) in Canada (SC) before 1st February 2017 [15] Updated 03 Feb 2017
08 Jan 2016 Regulatory Status FDA assigns PDUFA action date of 30/10/2016 for Sarilumab for Rheumatoid arthritis [17] Updated 09 Jan 2016
08 Jan 2016 Regulatory Status The US FDA accepts BLA for Sarilumab for Rheumatoid arthritis for review [17] Updated 09 Jan 2016
08 Nov 2015 Scientific Update Adverse events data from the phase III SARIL-RA-TARGET trial in Rheumatoid arthritis released by Sanofi and Regeneron Pharmaceuticals [39] Updated 19 Nov 2015
08 Nov 2015 Scientific Update Efficacy and adverse events data from the phase III SARIL-RA-TARGET trial in Rheumatoid arthritis presented at the 79th Annual Scientific Meeting of the American College of Rheumatology and the 50th Annual Meeting of the Association of Rheumatology and Health Professionals (ACR/ARHP-2015) [40] Updated 16 Nov 2015
30 Sep 2015 Phase Change - Preregistration Preregistration for Rheumatoid arthritis (Monotherapy) in USA (SC) Updated 09 Feb 2017
30 Sep 2015 Phase Change - Preregistration Preregistration for Rheumatoid arthritis in USA (SC) before September 2015 Updated 09 Nov 2015
22 May 2015 Active Status Review Phase-III development is still ongoing for Rheumatoid arthritis in World Updated 10 Sep 2015
21 May 2015 Scientific Update Efficacy and adverse events data from the phase III SARIL-RA-TARGET trial in Rheumatoid arthritis released by Regeneron and Sanofi [38] Updated 10 Jun 2015
05 May 2015 Trial Update Sanofi in collaboration with Regeneron initiates enrolment in a phase I trial for Rheumatoid arthritis in Japan (NCT02404558) Updated 10 Jun 2015
04 May 2015 Trial Update Regeneron Pharmaceuticals in collaboration with Sanofi completes a phase I study in Rheumatoid arthritis in USA (NCT02097524) Updated 10 Jun 2015
01 May 2015 Trial Update Sanofi completes the phase III SARIL-RA-ONE trial US, the Czech Republic, Estonia, Chile, Poland, Russia and Hungary (NCT02121210) Updated 03 Jul 2015
07 Apr 2015 Trial Update Sanofi plans a phase I trial in Rheumatoid arthritis in Japan (NCT02404558) Updated 07 Apr 2015
16 Feb 2015 Trial Update Sanofi terminates phase III trial in Rheumatoid arthritis in USA, European Union, Argentina, Brazil, Chile, Colombia, Ecuador, Israel, South Korea, Malaysia, Mexico, New Zealand, Peru, Russia, Ukraine, South Africa, Taiwan, Thailand and Peru (NCT01764997) Updated 10 Mar 2015
01 Feb 2015 Phase Change - III Phase-III clinical trials in Rheumatoid arthritis (Monotherapy) in Ukraine, Peru, South Africa, South Korea, Israel (SC) (SARIL-RA-MONARCH) (NCT02332590) Updated 09 Feb 2017
01 Feb 2015 Trial Update Regeneron Pharmaceutics initiates enrolment in the SARIL-RA-MONARCH trial for Rheumatoid arthritis (Monotherapy) in Czech Republic, Germany, Poland, Romania, Spain, United Kingdom after February 2015 (NCT02332590) Updated 23 Nov 2016
01 Feb 2015 Trial Update Sanofi initiates enrolment in the phase III SARIL-RA-HARUKA trial for Rheumatoid arthritis (Adjunctive therapy) in Japan (NCT02373202) Updated 06 Mar 2015
31 Jan 2015 Trial Update Sanofi and Regeneron initiate the phase III SARIL-RA-MONARCH trial for Rheumatoid arthritis in USA and Hungary (NCT02332590; EudraCT2014-002541-22) Updated 13 Feb 2015
12 Jan 2015 Trial Update Sanofi and Regeneron plan the phase III SARIL-RA-MONARCH trial for Rheumatoid arthritis in USA and Hungary (NCT02332590; EudraCT2014-002541-22) Updated 12 Jan 2015
01 Nov 2014 Phase Change - III Phase-III clinical trials in Rheumatoid arthritis in Japan (SC) Updated 24 Nov 2014
01 Oct 2014 Trial Update Sanofi completes a phase III trial in Rheumatoid arthritis (Second-line therapy or greater) in US, Belgium, Czech Republic, Estonia, Finland, Hungary, Norway, the Netherlands, the UK, Poland, Spain and Sweden (SC) (NCT01768572) Updated 05 Dec 2014
12 Jun 2014 Scientific Update Efficacy and adverse events data from the phase III SARIL-RA-MOBILITY trial in Rheumatoid arthritis (Adjunctive treatment, Monotherapy) presented at the Annual Congress of the European League Against Rheumatism (EULAR-2014) [32] Updated 19 Jun 2014
01 Jun 2014 Phase Change - III Phase-III clinical trials in Rheumatoid arthritis (Monotherapy) in Russia, Chile (SC) (NCT02121210) Updated 09 Feb 2017
01 Jun 2014 Trial Update Sanofi and Regeneron initiate a phase III trial for Rheumatoid arthritis (Monotherapy) in Czech Republic, Estonia and Hungary (NCT02121210) Updated 12 Aug 2014
21 Apr 2014 Trial Update Sanofi and Regeneron plan a phase III trial for Rheumatoid arthritis in the USA (NCT02121210) Updated 29 Apr 2014
31 Mar 2014 Trial Update Sanofi & Regeneron initiate enrolment in the phase III SARIL-RA-EASY trial for Rheumatoid arthritis in USA, Chile, Mexico, Poland, Russia and South Africa (NCT02057250) Updated 29 Apr 2014
26 Mar 2014 Trial Update Regeneron initiates enrolment in a phase I trial for Rheumatoid arthritis in the USA (NCT02097524) Updated 01 Apr 2014
26 Feb 2014 Trial Update Sanofi plans a phase III usability study of the sarilumab auto-injector device for Rheumatoid arthritis in USA (NCT02057250) Updated 26 Feb 2014
01 Jan 2014 Phase Change - I Phase-I clinical trials in Rheumatoid arthritis in Moldova (SC) (NCT02017639) Updated 21 Apr 2016
01 Jan 2014 Trial Update Regeneron and Sanofi initiate enrolment in a phase I drug interaction trial for Rheumatoid arthritis in USA and South Korea (NCT02017639) Updated 03 Feb 2014
01 Dec 2013 Trial Update Sanofi & Regeneron complete a phase I trial in Rheumatoid arthritis in Japan (NCT01850680) Updated 18 Mar 2014
22 Nov 2013 Scientific Update Efficacy & adverse events data from the phase III SARIL-RA-MOBILITY trial in Rheumatoid arthritis (Adjunctive treatment, Monotherapy) released by Sanofi & Regeneron [33] Updated 05 Dec 2013
31 Oct 2013 Trial Update Sanofi completes a phase II/III trial in Rheumatoid arthritis worldwide (NCT01061736) Updated 21 Nov 2013
02 Sep 2013 Phase Change - II Phase-II clinical trials in Uveitis in Germany (SC) after September 2013 (EudraCT2012-004845-34) Updated 03 Feb 2014
22 Aug 2013 Phase Change - III Phase-III clinical trials in Rheumatoid arthritis in France, Israel and Latvia (SC) prior to August 2013 (RA-COMPARE; NCT01764997; EudraCT 2012-001984-66) Updated 22 Aug 2013
26 Jul 2013 Trial Update Sanofi and Regeneron plan a phase II trial for Uveitis in USA (NCT01900431) Updated 26 Jul 2013
11 Jul 2013 Phase Change - II Phase-II clinical trials in Uveitis in USA, Czech Republic, France and Turkey after July 2013 (SC) (NCT01900431) Updated 06 Dec 2013
11 Jul 2013 Phase Change - II Phase-II clinical trials in Uveitis in Italy and Spain (SC) (NCT01900431) Updated 11 Sep 2013
17 May 2013 Phase Change - III Phase-III clinical trials in Rheumatoid arthritis (Adjunctive treatment) in Argentina, Austria, Belgium, Portugal, Belarus, Egypt, Germany, India, Malaysia, New Zealand, Philippines, Spain, Taiwan and Thailand (SC) before May 2013 (MOBILITY, NCT01061736) Updated 17 May 2013
17 May 2013 Phase Change - III Phase-III clinical trials in Rheumatoid arthritis (Adjunctive treatment) in Sweden (SC) (ASCERTAIN, NCT01768572) Updated 17 May 2013
17 May 2013 Phase Change - III Phase-III clinical trials in Rheumatoid arthritis in Slovakia (SC) (TARGET, NCT01709578) Updated 17 May 2013
30 Apr 2013 Phase Change - I Phase-I clinical trials in Rheumatoid arthritis in Japan (SC) Updated 19 Jun 2013
30 Apr 2013 Trial Update Sanofi initiates enrolment in the RA-COMPARE phase III trial for Rheumatoid arthritis (Adjunctive treatment) in USA (NCT01764997) Updated 10 May 2013
25 Apr 2013 Phase Change - III Phase-III clinical trials in Rheumatoid arthritis in Italy after April 2013 (SC) Updated 28 Feb 2014
25 Apr 2013 Phase Change - III Phase-III clinical trials in Rheumatoid arthritis (Adjunctive treatment) in United Kingdom (SC) (RA-COMPARE, EudraCT 2012-001984-66) Updated 17 May 2013
01 Apr 2013 Phase Change - III Phase-III clinical trials in Rheumatoid arthritis in Ecuador and Peru (SC) (NCT01764997) after April 2013 Updated 10 Mar 2015
01 Mar 2013 Trial Update Sanofi initiates enrolment in a phase III SARIL-RA-ASCERTAIN trial in Rheumatoid arthritis in USA (NCT01768572) Updated 22 Apr 2013
21 Feb 2013 Trial Update Sanofi plans a phase III SARIL-RA-ASCERTAIN trial in Rheumatoid arthritis in USA (NCT01768572) Updated 21 Feb 2013
19 Feb 2013 Trial Update Sanofi plans a phase III RA-COMPARE trial in Rheumatoid arthritis in World (NCT01764997) Updated 19 Feb 2013
07 Feb 2013 Phase Change - Discontinued(II) Discontinued - Phase-II for Ankylosing spondylitis in Germany and Turkey (SC) Updated 10 May 2013
07 Feb 2013 Phase Change - Discontinued(III) Discontinued - Phase-III for Ankylosing spondylitis in USA, Canada, Australia, Austria, Belgium, Czech Republic, France, Hungary, Lithuania, Netherlands, Poland and Spain (SC) Updated 10 May 2013
29 Oct 2012 Trial Update Regeneron and Sanofi plan a phase III trial of sarilumab in Rheumatoid arthritis in the US(NCT01709578) Updated 29 Oct 2012
01 Oct 2012 Trial Update Sanofi initiates enrolment in a phase III SARIL-RA-TARGET trial in Rheumatoid arthritis in USA (NCT01709578) Updated 19 Feb 2013
10 Jan 2012 Trial Update Sanofi and Regeneron discontinue a phase III long-term extention trial in Ankylosing spondylitis in World (NCT01118728) Updated 02 Feb 2012
30 Sep 2011 Trial Update Sanofi-aventis & Regeneron complete a phase I trial in Rheumatoid arthritis in USA(NCT01328522) Updated 09 Nov 2011
27 Sep 2011 Phase Change - Discontinued(II) Discontinued - Phase-II for Rheumatoid arthritis in Germany (SC) Updated 11 Oct 2011
27 Sep 2011 Phase Change - Discontinued(II) Discontinued - Phase-II for Rheumatoid arthritis in Italy (SC) Updated 11 Oct 2011
27 Sep 2011 Phase Change - Discontinued(II) Discontinued - Phase-II for Rheumatoid arthritis in Spain (SC) Updated 11 Oct 2011
05 Sep 2011 Trial Update Sanofi-aventis completes enrolment in its phase I trial for Rheumatoid arthritis in US (NCT01328522) Updated 15 Sep 2011
12 Jul 2011 Phase Change - III Phase-III clinical trials in Rheumatoid arthritis (Adjunctive treatment) in Brazil (SC) Updated 13 Jul 2011
12 Jul 2011 Phase Change - III Phase-III clinical trials in Rheumatoid arthritis (Adjunctive treatment) in Canada (SC) Updated 13 Jul 2011
12 Jul 2011 Phase Change - III Phase-III clinical trials in Rheumatoid arthritis (Adjunctive treatment) in Colombia (SC) Updated 13 Jul 2011
12 Jul 2011 Phase Change - III Phase-III clinical trials in Rheumatoid arthritis (Adjunctive treatment) in Czech Republic (SC) Updated 13 Jul 2011
12 Jul 2011 Phase Change - III Phase-III clinical trials in Rheumatoid arthritis (Adjunctive treatment) in Finland (SC) Updated 13 Jul 2011
12 Jul 2011 Phase Change - III Phase-III clinical trials in Rheumatoid arthritis (Adjunctive treatment) in Hungary (SC) Updated 13 Jul 2011
12 Jul 2011 Phase Change - III Phase-III clinical trials in Rheumatoid arthritis (Adjunctive treatment) in Norway (SC) Updated 13 Jul 2011
12 Jul 2011 Phase Change - III Phase-III clinical trials in Rheumatoid arthritis (Adjunctive treatment) in Russia (SC) Updated 13 Jul 2011
12 Jul 2011 Phase Change - III Phase-III clinical trials in Rheumatoid arthritis (Adjunctive treatment) in South Africa (SC) Updated 13 Jul 2011
12 Jul 2011 Phase Change - III Phase-III clinical trials in Rheumatoid arthritis (Adjunctive treatment) in Turkey (SC) Updated 13 Jul 2011
12 Jul 2011 Scientific Update Efficacy and adverse events data from a phase IIb trial in Ankylosing spondylitis released by sanofi aventis and Regeneron [35] Updated 13 Jul 2011
12 Jul 2011 Scientific Update Phase II efficacy and adverse events data from a phase II/III trial in Rheumatoid arthritis (Adjunctive treatment) released by sanofi aventis and Regeneron [35] Updated 13 Jul 2011
08 Jun 2011 Trial Update Sanofi-Aventis completes a phase II trial in Ankylosing spondylitis in USA, Canada, Australia, Austria, Belgium, Czech Republic, France, Germany, Hungary, Lithuania, Netherlands, Poland, Spain and Turkey (NCT01061723) Updated 29 Jun 2011
31 May 2011 Trial Update Sanofi-Aventis completes enrolment in its phase II trial for Rheumatoid arthritis in USA, Brazil, Canada, Colombia, Czech Republic, Germany, Hungary, Italy, Mexico, Norway and Spain (NCT01217814) Updated 18 Jun 2011
31 May 2011 Trial Update Sanofi-Aventis initiates enrolment in a phase I trial for Rheumatoid arthritis in USA (NCT01328522) Updated 17 Jun 2011
06 May 2011 Company Involvement sanofi-aventis is now called Sanofi Updated 17 Feb 2012
08 Apr 2011 Phase Change - II/III Phase-II/III clinical trials in Rheumatoid arthritis in Canada (SC) Updated 19 Apr 2011
08 Apr 2011 Phase Change - II/III Phase-II/III clinical trials in Rheumatoid arthritis in Norway (SC) Updated 19 Apr 2011
02 Dec 2010 Phase Change - II Phase-II clinical trials in Ankylosing spondylitis in Turkey (SC) Updated 05 Apr 2011
30 Nov 2010 Phase Change - II Phase-II clinical trials in Rheumatoid arthritis (Adjunctive treatment) in Spain (SC) Updated 13 Jul 2011
30 Nov 2010 Phase Change - II Phase-II clinical trials in Rheumatoid arthritis in Brazil (SC) Updated 18 Jun 2011
30 Nov 2010 Phase Change - II Phase-II clinical trials in Rheumatoid arthritis in Colombia (SC) Updated 18 Jun 2011
30 Nov 2010 Phase Change - II Phase-II clinical trials in Rheumatoid arthritis in Germany (SC) Updated 18 Jun 2011
30 Nov 2010 Phase Change - II Phase-II clinical trials in Rheumatoid arthritis in Italy (SC) Updated 18 Jun 2011
11 Nov 2010 Scientific Update Adverse events and pharmacodynamics data from three phase I trials in Rheumatoid arthritis presented at the 74th Annual Scientific Meeting of the American College of Rheumatology and the 45th Annual Meeting of the Association of Rheumatology Health (ACR/ARHP-2010) [92] Updated 07 Dec 2010
30 Jun 2010 Phase Change - III Phase-III clinical trials in Rheumatoid arthritis in Estonia (SC) Updated 03 Nov 2010
30 Jun 2010 Phase Change - III Phase-III clinical trials in Rheumatoid arthritis in Mexico (SC) Updated 03 Nov 2010
30 Jun 2010 Phase Change - III Phase-III clinical trials in Rheumatoid arthritis (in combination with disease-modifying antirheumatics) in USA (SC) Updated 06 Jul 2010
15 Jun 2010 Phase Change - III Phase-III clinical trials in Rheumatoid arthritis (Adjunctive treatment) in Greece (SC) Updated 13 Jul 2011
15 Jun 2010 Phase Change - III Phase-III clinical trials in Rheumatoid arthritis (Adjunctive treatment) in Lithuania (SC) Updated 13 Jul 2011
15 Jun 2010 Phase Change - III Phase-III clinical trials in Rheumatoid arthritis (Adjunctive treatment) in Netherlands (SC) Updated 13 Jul 2011
15 Jun 2010 Phase Change - III Phase-III clinical trials in Rheumatoid arthritis (Adjunctive treatment) in Romania (SC) Updated 13 Jul 2011
15 Jun 2010 Phase Change - III Phase-III clinical trials in Rheumatoid arthritis (Adjunctive treatment) in South Korea (SC) Updated 13 Jul 2011
15 Jun 2010 Phase Change - III Phase-III clinical trials in Rheumatoid arthritis (Adjunctive treatment) in Ukraine (SC) Updated 13 Jul 2011
15 Jun 2010 Phase Change - III Phase-III clinical trials in Rheumatoid arthritis in Australia (SC) Updated 03 Nov 2010
15 Jun 2010 Phase Change - III Phase-III clinical trials in Rheumatoid arthritis in Chile (SC) Updated 03 Nov 2010
15 Jun 2010 Phase Change - III Phase-III clinical trials in Rheumatoid arthritis in Poland (SC) Updated 03 Nov 2010
15 Jun 2010 Phase Change - III Phase-III clinical trials in Rheumatoid arthritis in USA (SC) Updated 03 Nov 2010
01 Jun 2010 Phase Change - III Phase-III clinical trials in Ankylosing spondylitis in Australia (SC) Updated 13 Jul 2011
01 Jun 2010 Phase Change - III Phase-III clinical trials in Ankylosing spondylitis in Austria (SC) Updated 13 Jul 2011
01 Jun 2010 Phase Change - III Phase-III clinical trials in Ankylosing spondylitis in Belgium (SC) Updated 13 Jul 2011
01 Jun 2010 Phase Change - III Phase-III clinical trials in Ankylosing spondylitis in Canada (SC) Updated 13 Jul 2011
01 Jun 2010 Phase Change - III Phase-III clinical trials in Ankylosing spondylitis in Czech Republic (SC) Updated 13 Jul 2011
01 Jun 2010 Phase Change - III Phase-III clinical trials in Ankylosing spondylitis in France (SC) Updated 13 Jul 2011
01 Jun 2010 Phase Change - III Phase-III clinical trials in Ankylosing spondylitis in Hungary (SC) Updated 13 Jul 2011
01 Jun 2010 Phase Change - III Phase-III clinical trials in Ankylosing spondylitis in Lithuania (SC) Updated 13 Jul 2011
01 Jun 2010 Phase Change - III Phase-III clinical trials in Ankylosing spondylitis in Netherlands (SC) Updated 13 Jul 2011
01 Jun 2010 Phase Change - III Phase-III clinical trials in Ankylosing spondylitis in Poland (SC) Updated 13 Jul 2011
01 Jun 2010 Phase Change - III Phase-III clinical trials in Ankylosing spondylitis in Spain (SC) Updated 13 Jul 2011
01 Jun 2010 Phase Change - III Phase-III clinical trials in Ankylosing spondylitis in USA (SC) Updated 13 Jul 2011
31 Mar 2010 Phase Change - II/III Phase-II/III clinical trials in Rheumatoid arthritis in Russia (SC) Updated 03 Nov 2010
31 Mar 2010 Phase Change - III Phase-III clinical trials in Rheumatoid arthritis in Poland (SC) Updated 03 Nov 2010
09 Mar 2010 Phase Change - II/III Phase-II/III clinical trials in Rheumatoid arthritis in Czech Republic (SC) Updated 03 Nov 2010
09 Mar 2010 Phase Change - II/III Phase-II/III clinical trials in Rheumatoid arthritis in Finland (SC) Updated 03 Nov 2010
09 Mar 2010 Phase Change - II/III Phase-II/III clinical trials in Rheumatoid arthritis in Hungary (SC) Updated 03 Nov 2010
09 Mar 2010 Phase Change - II/III Phase-II/III clinical trials in Rheumatoid arthritis in South Africa (SC) Updated 03 Nov 2010
09 Mar 2010 Phase Change - II/III Phase-II/III clinical trials in Rheumatoid arthritis in Turkey (SC) Updated 03 Nov 2010
09 Mar 2010 Phase Change - II/III Phase-II/III clinical trials in Rheumatoid arthritis in Australia (SC) Updated 31 May 2010
09 Mar 2010 Phase Change - II/III Phase-II/III clinical trials in Rheumatoid arthritis in Chile (SC) Updated 31 May 2010
09 Mar 2010 Phase Change - II/III Phase-II/III clinical trials in Rheumatoid arthritis in USA (SC) Updated 12 Mar 2010
28 Feb 2010 Phase Change - II Phase-II clinical trials in Ankylosing spondylitis in Australia (SC) Updated 03 Nov 2010
28 Feb 2010 Phase Change - II Phase-II clinical trials in Ankylosing spondylitis in Austria (SC) Updated 03 Nov 2010
28 Feb 2010 Phase Change - II Phase-II clinical trials in Ankylosing spondylitis in Belgium (SC) Updated 03 Nov 2010
28 Feb 2010 Phase Change - II Phase-II clinical trials in Ankylosing spondylitis in Czech Republic (SC) Updated 03 Nov 2010
28 Feb 2010 Phase Change - II Phase-II clinical trials in Ankylosing spondylitis in France (SC) Updated 03 Nov 2010
28 Feb 2010 Phase Change - II Phase-II clinical trials in Ankylosing spondylitis in Germany (SC) Updated 03 Nov 2010
28 Feb 2010 Phase Change - II Phase-II clinical trials in Ankylosing spondylitis in Hungary (SC) Updated 03 Nov 2010
28 Feb 2010 Phase Change - II Phase-II clinical trials in Ankylosing spondylitis in Lithuania (SC) Updated 03 Nov 2010
28 Feb 2010 Phase Change - II Phase-II clinical trials in Ankylosing spondylitis in Netherlands (SC) Updated 03 Nov 2010
28 Feb 2010 Phase Change - II Phase-II clinical trials in Ankylosing spondylitis in Poland (SC) Updated 03 Nov 2010
28 Feb 2010 Phase Change - II Phase-II clinical trials in Ankylosing spondylitis in Spain (SC) Updated 03 Nov 2010
28 Feb 2010 Phase Change - II Phase-II clinical trials in Ankylosing spondylitis in Canada (SC) Updated 12 Mar 2010
28 Feb 2010 Phase Change - II Phase-II clinical trials in Ankylosing spondylitis in USA (SC) Updated 12 Mar 2010
30 Sep 2008 Phase Change - I Phase-I clinical trials in Rheumatoid arthritis in Russia (SC) Updated 12 Mar 2010
29 Nov 2007 Phase Change - I Phase-I clinical trials in Rheumatoid arthritis in USA (SC) Updated 03 Mar 2008

References

  1. Combined General Shareholder Meeting of May 6, 2011.

    Media Release
  2. HHS Funds Phase 2/3 Clinical Trial for Potential Treatment for COVID-19.

    Media Release
  3. Regeneron Reports First Quarter 2020 Financial and Operating Results.

    Media Release
  4. Regeneron Initiates Major Global Collaboration with Sanofi-aventis to Develop and Commercialize Fully-Human Therapeutic Antibodies.

    Media Release
  5. Sanofi-aventis initiates a major global collaboration with Regeneron to develop and commercialize fully-human therapeutic antibodies and plans to increase its stake in Regeneron to approximately 19 %.

    Media Release
  6. Sanofi-aventis and Regeneron Expand Strategic Antibody Collaboration.

    Media Release
  7. Regeneron Announces Amendment to Investor Agreement with Sanofi.

    Media Release
  8. Sanofi and Regeneron announce intent to restructure Antibody collaboration for Kevzara(Rm) (sarilumab) and Praluent(Rm) (alirocumab).

    Media Release
  9. Sanofi finalizes Praluent(Rm) (alirocumab) restructuring with Regeneron.

    Media Release
  10. Sanofi and Asahi Kasei Pharma enter license agreement for marketing of Kevzara(R) Subcutaneous Injection, a treatment for rheumatoid arthritis, in Japan.

    Media Release
  11. Asahi Kasei Pharma launched Kevzara(R) Subcutaneous Injection, a treatment for rheumatoid arthritis, in Japan.

    Media Release
  12. Sanofi and Regeneron Announce FDA Approval of Kevzara(Rm) (sarilumab) for the Treatment of Moderately to Severely Active Rheumatoid Arthritis in Adult Patients.

    Media Release
  13. REGENERON AND SANOFI ANNOUNCE KEVZARA(R) (SARILUMAB) BIOLOGICS LICENSE APPLICATION RESUBMISSION ACCEPTED FOR REVIEW BY U.S. FDA.

    Media Release
  14. Regeneron and Sanofi Announce First Approval of Kevzara(T) (sarilumab) for the Treatment of Moderately to Severely Active Rheumatoid Arthritis in Adult Patients by Health Canada.

    Media Release
  15. Sanofi and Regeneron Announce First Approval of Kevzara(T) (sarilumab) for the Treatment of Moderately to Severely Active Rheumatoid Arthritis in Adult Patients by Health Canada.

    Media Release
  16. Regeneron and Sanofi Receive Complete Response Letter from FDA for Sarilumab, an Investigational Treatment for Rheumatoid Arthritis.

    Media Release
  17. Regeneron and Sanofi Announce Sarilumab Biologics License Application Accepted for Review by US FDA.

    Media Release
  18. Regeneron Reports Third Quarter 2015 Financial and Operating Results.

    Media Release
  19. Regeneron Reports Fourth Quarter and Full Year 2014 Financial and Operating Results.

    Media Release
  20. Sanofi Announces Licensing of Kevzara(R) (sarilumab) to Treat Adult Patients with Moderately to Severely Active Rheumatoid Arthritis (RA) in the European Union.

    Media Release
  21. Sanofi and Regeneron Receive CHMP Positive Opinion for Kevzara(Rm) (sarilumab) to Treat Adult Patients with Moderately to Severely Active Rheumatoid Arthritis.

    Media Release
  22. Meeting highlights from the Committee for Medicinal Products for Human Use (CHMP) 18-21 April 2017.

    Media Release
  23. Sanofi and Regeneron Announce EMA Acceptance for Review of Marketing Authorisation Application for Sarilumab.

    Media Release
  24. Regeneron Reports Third Quarter 2017 Financial and Operating Results.

    Media Release
  25. Regeneron Reports Third Quarter 2016 Financial and Operating Results.

    Media Release
  26. Kevzara(T) (sarilumab) now available in Canada for the Treatment of Adult Patients with Moderately to Severely Active Rheumatoid Arthritis.

    Media Release
  27. Product information - KEVZARA. Internet-Doc 2017;.

    Available from: URL: https://health-products.canada.ca/dpd-bdpp/info.do?code=94797&lang=en
  28. PRODUCT MONOGRAPH - KEVZARA? Internet-Doc 2017;.

    Available from: URL: https://health-products.canada.ca/dpd-bdpp/info.do?code=94797&lang=en
  29. Burmester GR, Lin Y, St John G, Wang S, Gomez-Reino JJ, Maldonado-Cocco JA, et al. Long-Term Efficacy with 5-Year-Radiographic Results and Safety of Sarilumab in Combination with Csdmards in Patients with Rheumatoid Arthritis. EULAR-2018 2018; abstr. SAT0172.

    Available from: URL: https://b-com.mci-group.com/Abstract/Statistics/AbstractStatisticsViewPage.aspx?AbstractID=394861
  30. Regeneron Reports Third Quarter 2012 Financial and Operating Results.

    Media Release
  31. A Randomized, Double-blind, Placebo-controlled, Multicenter, Two-part, Dose Ranging and Confirmatory Study With an Operationally Seamless Design, Evaluating Efficacy and Safety of SAR153191 on Top of Methotrexate (MTX) in Patients With Active Rheumatoid Arthritis Who Are Inadequate Responders to MTX Therapy

    ctiprofile
  32. Sanofi and Regeneron Announce New, Detailed Data from Positive Sarilumab Phase 3 Rheumatoid Arthritis Trial at EULAR.

    Media Release
  33. Sanofi and Regeneron Report Positive Results with Sarilumab in First Phase 3 Rheumatoid Arthritis Registration Trial.

    Media Release
  34. Sanofi and Regeneron Announce Patient Enrollment in Two Phase 3 Trials with Sarilumab in Rheumatoid Arthritis (RA).

    Media Release
  35. Sanofi and Regeneron Report Positive Phase 2b Trial Results with Sarilumab in Rheumatoid Arthritis.

    Media Release
  36. Positive Phase 2b Results with Sarilumab in Rheumatoid Arthritis to be Presented as a Late-Breaking Poster at the 2011 American College of Rheumatology Annual Meeting.

    Media Release
  37. Gabay C, Msihid J, Daskalakis N, Graham N, Barbot A, Zilberstein M, et al. Effect of Sarilumab on Circulating Biomarkers of Bone and Joint Destruction in Patients with Rheumatoid Arthritis with Inadequate Response to Methotrexate. ACR/ARHP-2016 2016; abstr. 3091.

    Available from: URL: http://acrabstracts.org/abstract/effect-of-sarilumab-on-circulating-biomarkers-of-bone-and-joint-destruction-in-patients-with-rheumatoid-arthritis-with-inadequate-response-to-methotrexate/
  38. Regeneron and Sanofi Announce Positive Topline Results from Phase 3 Studies with Sarilumab in Patients with Rheumatoid Arthritis.

    Media Release
  39. Sanofi and Regeneron Present Results from Pivotal Phase 3 Study of Sarilumab at American College of Rheumatology Annual Meeting.

    Media Release
  40. Regeneron and Sanofi Present Results from Pivotal Phase 3 Study of Sarilumab at American College of Rheumatology Annual Meeting.

    Media Release
  41. A Randomized, Double-blind, Parallel, Placebo-controlled Study Assessing The Efficacy and Safety of Sarilumab Added To DMARD Therapy In Patients With Rheumatoid Arthritis Who Are Inadequate Responders To Or Intolerant Of TNF-alpha Antagonists

    ctiprofile
  42. A Multicenter, Randomized, Open-Label, Parallel-Group Usability Study Of The Sarilumab Auto-Injector Device And A Prefilled Syringe In Patients With Moderate To Severe Active Rheumatoid Arthritis Who Are Candidates For Anti-IL6R Therapy

    ctiprofile
  43. A Randomized, Double-Blind, Double-Dummy Study Assessing The Safety and Tolerability of Sarilumab and Tocilizumab In Patients With Rheumatoid Arthritis Who Are Inadequate Responders to or Intolerant of TNF Antagonists

    ctiprofile
  44. Xu C, Nolain P, Lu Q, Paccaly A, Iglesias-Rodriguez M, St John G, et al. Sarilumab and Tocilizumab Receptor Occupancy (Ro), and Effects on C-Reactive Protein (Crp) Levels, in Patients with Rheumatoid Arthritis (Ra). EULAR-2019 2019; abstr. FRI0106.

    Available from: URL: http://scientific.sparx-ip.net/archiveeular/index.cfm?view=2&c=a&item=2019FRI0106
  45. A Randomized, Double-blind, Multicenter Study Evaluating the Safety and Efficacy of Sarilumab Added to Non-MTX DMARDs or as Monotherapy in Japanese Patients With Active Rheumatoid Arthritis

    ctiprofile
  46. A Randomized, Controlled Study of Sarilumab and Methotrexate (MTX) Versus Etanercept and MTX in Patients with Rheumatoid Arthritis (RA) and an Inadequate Response to 4 Months of Treatment with Adalimumab and MTX

    ctiprofile
  47. Burmester GR, Amital H, Rubbert-Roth A, van Hoogstraten H, Gervitz LM, Thangavelu K, et al. Patients (Pts) Switched to Sarilumab from Adalimumab Achieve Clinically Important Improvements in Ra Disease Activity: Results from Monarch Trial Open-Label Extension (Ole). EULAR-2019 2019; abstr. SAT0137.

    Available from: URL: http://scientific.sparx-ip.net/archiveeular/index.cfm?view=2&c=a&item=2019SAT0137
  48. Burmester GR, St John G, Iglesias-Rodriguez M, Hu C-C, Raskina T, Amital H, et al. Switching from Adalimumab to Sarilumab is Associated with Comparable Efficacy But Lower Functional Improvement Versus Continuous Sarilumab Monotherapy Through 48-Week Open-Label Extension (Ole) of the Phase 3 Monarch Trial. EULAR-2018 2018; abstr. SAT0183.

    Available from: URL: https://b-com.mci-group.com/Abstract/Statistics/AbstractStatisticsViewPage.aspx?AbstractID=394859
  49. Burmester GR, Fiore S, Hu C-C, Fay J, Lee EB, Genovese MC. Efficacy and Safety of Switching from Adalimumab to Sarilumab in an Open-Label Extension of a Phase 3 Monotherapy Trial in Patients with Active Rheumatoid Arthritis. ACR/ARHP-2017 2017; abstr. 2482.

    Available from: URL: http://acrabstracts.org/abstract/efficacy-and-safety-of-switching-from-adalimumab-to-sarilumab-in-an-open-label-extension-of-a-phase-3-monotherapy-trial-in-patients-with-active-rheumatoid-arthritis/
  50. Burmester G, Lin Y, Patel R, van Adelsberg J, Mangan E, van Hoogstraten H, et al. Efficacy and Safety of Sarilumab Versus Adalimumab in a Phase 3, Randomized, Double-Blind, Monotherapy Study in Patients with Active Rheumatoid Arthritis with Intolerance or Inadequate Response to Methotrexate. ACR/ARHP-2016 2016; abstr. 3221.

    Available from: URL: http://link.adisinsight.com/Ps8x5
  51. Regeneron and Sanofi Present Results from Phase 3 MONARCH Study of Investigational Sarilumab at American College of Rheumatology Annual Meeting.

    Media Release
  52. Regeneron and Sanofi Announce Topline Results of Phase 3 Monotherapy Study Demonstrating Superiority of Sarilumab vs. Adalimumab in Patients with Active Rheumatoid Arthritis.

    Media Release
  53. A Randomized, Double-blind, Parallel-group Study Assessing the Efficacy and Safety of Sarilumab Monotherapy Versus Adalimumab Monotherapy in Patients With Rheumatoid Arthritis

    ctiprofile
  54. A Multi-center, Uncontrolled Extension Study Evaluating Efficacy and Safety of SAR153191 in Patients With Active Rheumatoid Arthritis (RA)

    ctiprofile
  55. Genovese MC, Fay J, Parrino J, Beyer D, Iglesias-Rodriguez M, Graham N, et al. Sarilumab Dose Reduction in an Open-Label Extension Study in RA Patients. ACR/ARHP-2016 2016; abstr. 1631.

    Available from: URL: http://acrabstracts.org/abstract/sarilumab-dose-reduction-in-an-open-label-extension-study-in-ra-patients/
  56. A Randomized, Double-blind, Multicenter Study With a Placebo-controlled Period Assessing the Efficacy and Safety of Sarilumab Added to Methotrexate (MTX) in Japanese Patients With Moderately to Severely Active Rheumatoid Arthritis Who Are Inadequate Responders to MTX Therapy

    ctiprofile
  57. An Open-label, Randomized, Parallel Group Study Assessing the Immunogenicity and Safety of Sarilumab Administered as Monotherapy in Patients With Active Rheumatoid Arthritis

    ctiprofile
  58. A Randomized, Double-blind, Parallel-group, Placebo- and Active Calibrator-controlled Study Assessing the Clinical Benefit of SAR153191 Subcutaneous (SC) on Top of MTX in Patients With Active RA Who Have Failed Previous TNF-α Antagonists

    ctiprofile
  59. A Multi-center, Open-label, 2-treatment, Single-sequence Clinical Study to Evaluate the Effects of a Single 200 mg Subcutaneous Injection of Sarilumab on the Pharmacokinetics of a Single 40 mg Oral Dose of Simvastatin, With Optional 1-year Extension of Open Label Treatment of Sarilumab, in Patients With Rheumatoid Arthritis

    ctiprofile
  60. A Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study of the Safety and Tolerability of Subcutaneously Administered Sarilumab in Japanese Patients With Rheumatoid Arthritis Receiving Concomitant Methotrexate

    ctiprofile
  61. Regeneron Reports Fourth Quarter and Full Year 2007 Financial and Operating Results.

    Media Release
  62. Regeneron Reports Second Quarter 2010 Financial and Operating Results.

    Media Release
  63. A Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study of the Safety and Tolerability of Subcutaneously Administered REGN88/SAR153191 in Subjects With Rheumatoid Arthritis Receiving Concomitant Methotrexate.

    ctiprofile
  64. A Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Ascending Parallel-group Study of the Safety and Tolerability of REGN88 in Subjects With Rheumatoid Arthritis Receiving Concomitant Methotrexate.

    ctiprofile
  65. A Single-dose, Double-Blind, Placebo-Controlled, Parallel Group Safety, Tolerability and Pharmacodynamic Study of Subcutaneous REGN88 in Subjects With Rheumatoid Arthritis Receiving Concomitant Methotrexate.

    ctiprofile
  66. Single-dose Study to Describe the Pharmacodynamics (PD) and Safety of Sarilumab (REGN88/SAR153191) and Tocilizumab in Adults With Rheumatoid Arthritis (RA)

    ctiprofile
  67. Comparison of the Safety and Pharmacokinetics of Two SAR153191 (REGN88) Drug Products in Rheumatoid Arthritis Patients

    ctiprofile
  68. An Open-label, Randomized, Parallel Group, Single-dose Study to Describe the Safety of IL-6 Receptor Blockade With Sarilumab or Tocilizumab Monotherapy in Japanese Patients With Rheumatoid Arthritis

    ctiprofile
  69. An adaptive phase 2/3, randomized, double-blind, placebo-controlled, study assessing efficacy and safety of sarilumab for hospitalized patients with COVID-19

    ctiprofile
  70. Regeneron Announces Important Advances in Novel COVID-19 Antibody Program.

    Media Release
  71. Sanofi and Regeneron begin global Kevzara(Rm) (sarilumab) clinical trial program in patients with severe COVID-19.

    Media Release
  72. An Adaptive Phase 2/3, Randomized, Double-Blind, Placebo-Controlled Study Assessing Efficacy and Safety of Sarilumab for Hospitalized Patients With COVID-19

    ctiprofile
  73. Feinstein Institutes begins enrolling patients in multiple COVID-19 clinical trials.

    Media Release
  74. Regeneron and Sanofi Provide Update on U.S. Phase 2/3 Adaptive-Designed Trial of Kevzara(Rm) (sarilumab) in Hospitalized COVID-19 Patients.

    Media Release
  75. A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Sarilumab in Patients With Giant Cell Arteritis

    ctiprofile
  76. Sanofi delivers strong 2019 business EPS growth of 6.8% at CER.

    Media Release
  77. An Open-label, Sequential, Ascending, Repeated Dose-finding Study of Sarilumab, Administered with Subcutaneous (SC) Injection, in Children and Adolescents, Aged 1 to 17 Years, with Systemic Juvenile Idiopathic Arthritis (sJIA), Followed by an Extension Phase

    ctiprofile
  78. An Open-label, Sequential, Ascending, Repeated Dose-finding Study of Sarilumab, Administered with Subcutaneous (SC) Injection, in Children and Adolescents, Aged 2 to 17 Years, with Polyarticular-course Juvenile Idiopathic Arthritis (pcJIA) Followed by an Extension Phase

    ctiprofile
  79. De Benedetti F, Penades IC, Rubio Perez NE, Maschan A, Quartier P, ?uber Z, et al. Sarilumab, a Human Monoclonal Antibody to the Interleukin-6 (Il-6) Receptor, in Polyarticular-Course Juvenile Idiopathic Arthritis (Pcjia): a 12-Week Multinational Open-Label Dose-Finding Study. EULAR-2019 2019; abstr. FRI0549.

    Available from: URL: http://scientific.sparx-ip.net/archiveeular/index.cfm?view=2&c=a&item=2019FRI0549
  80. A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Sarilumab in Patients With Polymyalgia Rheumatica

    ctiprofile
  81. Regeneron Reports Second Quarter 2013 Financial and Operating Results.

    Media Release
  82. A Randomized, Double-Masked and Placebo-Controlled Study to Evaluate the Efficacy and Safety of Sarilumab Administered Subcutaneously Every 2 Weeks in Patients With Non-Infectious, Intermediate, Posterior or Pan-Uveitis (NIU)

    ctiprofile
  83. Regeneron Reports Second Quarter 2011 Financial and Operating Results.

    Media Release
  84. A Randomized Double Blind-placebo Controlled Dose Ranging Study to Evaluate the Efficacy and Safety of SAR153191 in Participants With Ankylosing Spondylitis (AS)

    ctiprofile
  85. Regeneron Pharmaceuticals SEC filing, FORM - 10K. Internet-Doc 2018;.

    Available from: URL: https://www.sec.gov/Archives/edgar/data/872589/000153217618000013/regn-123117x10k.htm
  86. Sanofi delivers 2018 business EPS growth of 5.1% at CER.

    Media Release
  87. Kevzara(R) (sarilumab) Data at the 2018 ACR/ARHP Annual Meeting Provide Additional Insight on Safety and Efficacy in Rheumatoid Arthritis.

    Media Release
  88. Sanofi: Q2 2018 Performance Positions Sanofi for New Growth Phase.

    Media Release
  89. Regeneron Collaboration Programs Highlighted During Sanofi Analyst Day.

    Media Release
  90. Regeneron Reports Second Quarter 2017 Financial and Operating Results.

    Media Release
  91. Sanofi and Regeneron Announce Kevzara(R) (sarilumab) Biologics License Application Resubmission Accepted for Review by US FDA.

    Media Release
  92. Radin AR, Mellis SJ, Jasson M, Nadler D, Belomestnov P, Wu R, et al. REGN88/SAR153191, a Fully-Human Interleukin-6 Receptor Monoclonal Antibody, Reduces Acute Phase Reactants in Patients with Rheumatoid Arthritis: Preliminary Observations from Phase 1 Studies. 74th-ACR-45th-ARHP-2010 2010; abstr. 1121.

    Available from: URL: http://www.rheumatology.org
  93. van der Heijde D, van Adelsberg J, van Hoogstraten H, Iglesias-Rodriguez M, Mangan E, Graham N, et al. Clinical and Radiographic Outcomes after 3 Years of Sarilumab in Patients with Rheumatoid Arthritis. ACR/ARHP-2016 2016; abstr. 1633.

    Available from: URL: http://acrabstracts.org/abstract/clinical-and-radiographic-outcomes-after-3-years-of-sarilumab-in-patients-with-rheumatoid-arthritis/
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