Type of information: Granting of a Market Authorisation in the EU
Product name: Kevzara®(sarilumab - REGN88/SAR153191)
Therapeutic area: Autoimmune diseases – Inflammatory diseases - Rheumatic diseases
- monoclonal antibody. Sarilumab (REGN88/SAR153191) is a fully human monoclonal antibody directed against the alpha subunit of the IL-6 receptor complex (IL-6R Alpha). Sarilumab is a high-affinity, subcutaneously delivered inhibitor of IL-6 signaling. It blocks the binding of IL-6 to its receptor and interrupts the resultant cytokine-mediated inflammatory signaling cascade. Sarilumab was developed using Regeneron's VelocImmune® antibody technology.
Company: Sanofi (France) Regeneron Pharmaceutical (USA - NY)
Disease: rheumatoid arthritis
- • On June 27, 2017, Sanofi and Regeneron Pharmaceuticals, announced that the European Commission has granted marketing authorization for Kevzara® (sarilumab) in combination with methotrexate for the treatment of moderately to severely active rheumatoid arthritis in adult patients who have responded inadequately to – or who are intolerant to – one or more disease modifying anti-rheumatic drugs .
- • On May 22, 2017, Sanofi and Regeneron Pharmaceuticals, announced the FDA approval of Kevzara® (sarilumab) for the treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to one or more disease modifying antirheumatic drugs, such as methotrexate. The approval of Kevzara® was based on data from approximately 2,900 adults with moderately to severely active rheumatoid arthritis who had
an inadequate response to previous treatment regimens. In two pivotal Phase 3 clinical trials, Kevzara® plus background
disease modifying anti-rheumatic drugs demonstrated statistically significant, clinically-meaningful improvements in patients with moderately to severely active rheumatoid arthritis. In the MOBILITY study, treatment with Kevzara® plus methotrexate reduced signs and symptoms, improved physical function, and demonstrated significantly less radiographic progression of structural damage, compared to placebo plus methotrexate.
- - At 24 weeks, patients treated with Kevzara® plus methotrexate achieved a greater improvement in the primary endpoint of signs and symptoms as measured by the proportion of patients achieving a 20 percent improvement in the American College of Rheumatology Criteria (ACR20) (Kevzara 200 mg, 66 percent; Kevzara 150 mg, 58 percent; placebo, 33percent)
- - At 52 weeks, patients treated with Kevzara plus methotrexate demonstrated significantly less radiographic progression of structural damage as measured by the change in modified Total Sharp Score, a key endpoint of the study (placebo,2.78; Kevzara 200 mg, 0.25; Kevzara 150 mg, 0.90)
- - At 16 weeks, patients treated with Kevzara plus methotrexate demonstrated greater improvement from baseline in physical
function as measured by the Health Assessment Questionnaire - Disability Index (HAQ-DI), a key endpoint of the study (Kevzara 200 mg, -0.58; Kevzara 150 mg, -0.54; placebo, -0.30)
In the TARGET study, treatment with Kevzara plus DMARD reduced signs and symptoms and improved physical function,
compared to placebo plus DMARD.
- At 24 weeks, patients treated with Kevzara plus DMARD achieved a greater improvement in the primary endpoint of
signs and symptoms as measured by the proportion of patients achieving an ACR20 response (Kevzara 200 mg, 61
percent; Kevzara 150 mg, 56 percent; placebo, 34 percent)
At 12 weeks, patients treated with Kevzara plus DMARD demonstrated greater improvement from baseline in physical
function as measured by HAQ-DI, a key endpoint of the study (Kevzara 200 mg, -0.49; Kevzara 150 mg, -0.50;
Patients treated with Kevzara are at increased risk of developing serious infections that may lead to hospitalization or death. The most common adverse reactions (occurring in at least 3 percent of patients treated with Kevzara in combination with DMARDs vs. placebo in combination with DMARDs) observed with Kevzara in the clinical studies were neutropenia (7- 10 percent vs. 0.2 percent), increased alanine aminotransferase (5 percent vs. 2 percent), injection site erythema (4-5 percent vs. 0.9 percent), upper respiratory infections (3-4 percent vs. 2 percent) and urinary tract infections (3 percent vs. 2 percent).
Sanofi and Regeneron have launched KevzaraConnect®, a comprehensive and specialized program that provides support services to patients throughout every step of the treatment process. KevzaraConnect will also help eligible patients who are uninsured, lack coverage, or need assistance with their out-of pocket copay costs. Additionally, KevzaraConnect offers personalized support from registered nurses and other specialists who are available 24/7 to speak with patients and help them navigate the complex insurance process.
- • On April 21, 2017, the European Medicine Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion for the marketing authorization of Kevzara® (sarilumab), recommending its approval for use in adult patients with moderately to severely active rheumatoid arthritis. The CHMP recommended the use of Kevzara® in combination with methotrexate for the treatment of moderately to severely active rheumatoid arthritis in adult patients who have responded inadequately to, or who are intolerant to one or more disease modifying anti-rheumatic drugs. Kevzara® can also be given as monotherapy in cases of intolerance to methotrexate or when treatment with methotrexate is inappropriate. The recommended dose of Kevzara® is 200 mg once every two weeks administered as a subcutaneous injection. Reduction of dose from 200 mg once every two weeks to 150 mg once every two weeks is recommended for management of neutropenia, thrombocytopenia, and liver enzyme elevations.
- The CHMP opinion is based on results from seven Phase 3 trials in the global SARIL-RA clinical development program, including SARIL-RA-MOBILITY, SARIL-RA-TARGET and SARIL-RA-MONARCH.
- • On October 28, 2016, Sanofi and Regeneron Pharmaceuticals announced the FDA issued a Complete Response Letter regarding the Biologics License Applications (BLA) for sarilumab for the treatment of adult patients with moderately to severely active rheumatoid arthritis. The letter refers to certain deficiencies identified during a routine good manufacturing practice inspection of the Sanofi Le Trait facility where sarilumab is filled and finished. Satisfactory resolution of these deficiencies is required before the BLA can be approved. 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. The letter does not identify any concerns relating to the safety or efficacy of sarilumab. If approved by the FDA, sarilumab would be commercialized by Regeneron and Sanofi Genzyme, the specialty care global business unit of Sanofi.
- • On January 8, 2016, Sanofi and Regeneron Pharmaceuticals announced that the FDA has accepted for review the Biologics License Application (BLA) for sarilumab intended for the treatment of patients with active, moderate-to-severe rheumatoid arthritis. Per the Prescription Drug User Fee Act (PDUFA), the target action date is Oct. 30, 2016.
- The BLA for sarilumab contains data from approximately 2,500 adults with active, moderate-to-severe rheumatoid arthritis who had an inadequate response to previous treatment regimens, including seven studies from the global SARIL-RA Phase 3 program. Last November, Regeneron Pharmaceuticals and Sanofi announced results from a pivotal Phase 3 study, SARIL-RA-TARGET at an oral session during the American College of Rheumatology Annual Meeting in San Francisco, California. The SARIL-RA-TARGET trial enrolled 546 RA patients who were inadequate responders or intolerant of TNF-alpha inhibitors . Patients were randomized to one of three treatment groups self-administered subcutaneously (SC) every other week : sarilumab 200 mg, sarilumab 150 mg, or placebo, in addition to non-biologic disease modifying antirheumaticdrugs therapy. Both sarilumab groups showed clinically relevant and statistically significant improvements compared to placebo in both coprimary endpoints. Improvements in signs and symptoms of RA at week 24, as measured by the proportion of patients achieving an ACR20 response were 61 percent in the sarilumab 200 mg group; 56 percent in the sarilumab 150 mg group; and 34 percent in the placebo group, all in combination with DMARD therapy.
Submission of marketing authorization application USA :
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization: 2017-05-22
UE authorization: 2017-06-27
Favourable opinion UE: 2017-04-21
Favourable opinion USA:
Orphan status USA:
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE: