Sanofi and Regeneron Pharmaceuticals, Inc., a leading science-based biopharmaceutical company, announced that the COMPARE and ASCERTAIN trials of sarilumab, the first fully human monoclonal antibody directed against the IL-6 receptor, which is delivered by subcutaneous injection every other week, have enrolled their first patients.
The broad SARIL-RA clinical development programme is focused on adult populations with moderate-to-severe rheumatoid arthritis (RA) who are inadequate responders to either methotrexate (MTX) or tumour necrosis factor alpha (TNF-alpha) inhibitor therapy. The SARIL-RA programme is comprised of the following five trials: SARIL-RA MOBILITY, SARIL-RA TARGET, SARIL-RA COMPARE, SARIL-RA ASCERTAIN, and an open-label extension trial, SARIL-RA EXTEND. The programme is targeted to enroll approximately 2,600 patients with moderate-to-severe rheumatoid arthritis. The primary objective of the overall phase 3 programme is to determine the safety and efficacy of sarilumab in reducing the signs and symptoms of RA, as well as inhibiting disease progression, in a broad range of patients. Two doses of sarilumab are being studied in the SARIL-RA program: 150 milligrams (mg) every other week and 200mg every other week.
The SARIL-RA ASCERTAIN trial is a multi-centre, randomized, double-blind, active-calibrator, phase 3 trial of 24 weeks that will assess the safety and tolerability of sarilumab and tocilizumab, both in combination with MTX, in patients with RA who are inadequate responders to, or intolerant of, TNF-alpha inhibitors. The primary endpoint of this study is safety.
“Despite the advances that TNF-alpha inhibitors have made in the management of patients with RA, up to 40 per cent of patients are inadequately controlled, as assessed by DAS 28 score, or are unable to tolerate the first TNF-alpha inhibitor prescribed,” said George D. Yancopoulos, chief scientific officer of Regeneron and president of Regeneron Laboratories. “The COMPARE trial will explore whether these patients would be better served by switching to a different mechanism of action, IL-6 inhibition, rather than administering another TNF-alpha inhibitor.”
The SARIL-RA COMPARE trial is a multi-centre, randomized, double-blind, active-control, phase 3 trial evaluating the safety and efficacy of sarilumab plus MTX compared to etanercept (a TNF-alpha inhibitor) plus MTX in adult patients with moderate-to-severe RA who demonstrate an inadequate response to adalimumab as their first TNF-alpha inhibitor therapy. COMPARE is designed to evaluate whether sarilumab is superior to etanercept when used in combination with MTX in this patient population. The primary endpoint of the study is the change in Disease Activity Score 28 based on C-reactive protein (DAS28-CRP) at 24 weeks. COMPARE is an international trial that expects to include 700 patients at approximately 300 sites.
“What is unique about the COMPARE study is that it will examine patients with RA who have not responded to their first TNF-alpha inhibitor and compare the safety and efficacy of a second TNF-alpha inhibitor versus a different class of therapy, an IL-6R inhibitor, sarilumab,” said Jorge Insuasty, vice president, Global R&D and deputy to the president for development, Sanofi. “The initiation of the SARIL-RA COMPARE and ASCERTAIN studies represents a significant step in the phase 3 SARIL-RA clinical development programme.”
"The full SARIL-RA phase 3 clinical programme is a robust program aimed to provide informative data on the anti-IL6R class of therapies. The COMPARE study will bring new data to the forefront in answering a key question," said Dr. Mark Genovese, Professor of Medicine, Division of Immunology and Rheumatology, Stanford University.
Sarilumab (REGN88/SAR153191) is the first 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.
The SARIL-RA phase 3 programme consists of 5 studies and is targeted to enroll approximately 2,600 adults with moderate-to-severe rheumatoid arthritis who have not had sufficient results with other treatment regimens. The goal of the programme is to evaluate the safety and efficacy of sarilumab in combination with methotrexate (MTX) in reducing the signs and symptoms and inhibiting the radiographic progression of RA.
Sanofi, an integrated global healthcare leader, discovers, develops and distributes therapeutic solutions focused on patients’ needs.
Regeneron is a leading science-based biopharmaceutical company based in Tarrytown, New York that discovers, invents, develops, manufactures, and commercializes medicines for the treatment of serious medical conditions.