Regeneron and Sanofi report that a phase 3 trial shows the investigational drug sarilumab is superior to adalimumab (Humira) for treatment of clinical signs and symptoms of active rheumatoid arthritis (RA) in adults.
Sarilumab is a human monoclonal antibody that acts against the interleukin-6 (IL-6) receptor, blocking the inflammatory IL-6 cytokine pathway.
The double-blind trial randomized 369 patients with active RA to receive either subcutaneous sarilumab monotherapy (200 mg every 2 weeks) or adalimumab monotherapy (40 mg every 2 weeks, with possibility to increase to weekly if unresponsive). Subjects were not candidates for methotrexate.
Patients treated with sarilumab experienced a greater reduction in disease activity, with a mean decrease in DAS28-ESR score (a standardized measure of RA activity) of 3.28 compared with 2.22 for adalimumab (P<0.0001).
"In this study, sarilumab monotherapy provided stronger efficacy than adalimumab monotherapy. Adalimumab is one of the most commonly used biologic medicines in RA," said Janet van Adelsberg, MD, senior director of Clinical Sciences, Immunology and Inflammation at Regeneron. "This is the first time an IL-6 receptor blocker delivered subcutaneously has demonstrated superiority over adalimumab monotherapy in RA."
According to Regeneron, the study also met important secondary endpoints, including a greater majority (72%) of sarilumab subjects achieving a 20% improvement in the American College of Rheumatology (ACR) criteria (ACR20) compared to those on adalimumab (58%) (P<0.01). A higher proportion of subjects reported 50% (ACR50: 45% with sarilumab vs. 29% with adalimumab, p=0.0017) and 70% improvements (ACR70: 23% with sarilumab vs. 11% for adalimumab, p=0.0036). In addition, rates of DAS28-ESR remission (score <2.6) and improvements in the Health Assessment Questionnaire - Disability Index (HAQ-DI) were significantly higher for sarilumab.
The incidence of adverse events was generally similar across both groups; however, neutropenia and injection site erythema were more common with sarilumab. The safety and efficacy data have yet to be fully evaluated by any regulatory authority. If approved, sarilumab would be one of several competitors for AbbVie’s blockbuster adalimumab therapy, Humira, which will lose patent protection in December 2016.