Type of information: Positive opinion for the granting of a Market Authorisation in the EU
Product name: Kevzara®(sarilumab - REGN88/SAR153191)
Therapeutic area: Autoimmune diseases – Inflammatory diseases - Rheumatic diseases
Action mechanism: 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 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 (DMARDs). 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. These studies incorporate data from more than 3,300 adults with moderately to severely active RA who have had an inadequate response or intolerance to one or more biologic or non-biologic DMARDs.
- • On October 28, 2016, Sanofi and Regeneron Pharmaceuticals announced the FDA issued a Complete Response Letter (CRL) regarding the Biologics License Applications (BLA) for sarilumab for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA). The CRL 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 CRL 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. Per the Prescription Drug User Fee Act (PDUFA), the target action date is Oct. 30, 2016. Sarilumab is an investigational, human monoclonal antibody directed against the IL-6 receptor that is intended for the treatment of patients with active, moderate-to-severe rheumatoid arthritis (RA). The BLA for sarilumab contains data from approximately 2,500 adults with active, moderate-to-severe RA who had an inadequate response to previous treatment regimens, including seven studies from the global SARIL-RA Phase 3 program. The goal of the ongoing global clinical development program is to evaluate the safety and efficacy of subcutaneous sarilumab, either as monotherapy or in combination with conventional disease-modifying anti-rheumatic drugs (DMARDs), including methotrexate (MTX), in reducing the signs and symptoms and inhibiting the radiographic progression of RA.
- 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 (ACR) 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 (TNF-IR). Patients were randomized to one of three treatment groups self-administered subcutaneously (SC) every other week (Q2W): sarilumab 200 milligrams (mg), sarilumab 150 mg, or placebo, in addition to non-biologic disease modifying antirheumaticdrugs (DMARD) 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 (p less than 0.0001).
Submission of marketing authorization application USA :
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
Favourable opinion UE:
Favourable opinion USA:
Orphan status USA:
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE: