A phase 3 monotherapy study has met its primary endpoint, demonstrating that sarilumab (Regeneron Pharmaceuticals/Sanofi) was superior to adalimumab (Humira, AbbVie) in improving signs and symptoms in patients with active rheumatoid arthritis (RA) at week 24. The study, SARIL-RA-MONARCH, also met important secondary endpoints, including other measures assessing improvements in the signs and symptoms of RA and physical function.

Sarilumab is an investigational human monoclonal antibody directed against the interleukin-6 (IL-6) receptor that inhibits the inflammatory activity in RA mediated by the IL-6 signaling pathway. IL-6 is the most abundant cytokine in the serum and synovial fluid of patients with RA, and levels of IL-6 correlate with both disease activity and joint destruction.

The SARIL-RA-MONARCH study enrolled 369 adult patients with active RA who were inadequate responders to, intolerant of, or inappropriate candidates for methotrexate. Patients were randomly assigned to receive either subcutaneous sarilumab monotherapy (200 mg every two weeks) or adalimumab monotherapy (40 mg every two weeks); patients who did not respond adequately to adalimumab could receive weekly dosing.

The trial’s primary endpoint was the change from baseline on the Disease Activity Score 28–Erythrocyte Sedimentation Rate (DAS28-ESR) at 24 weeks, which demonstrated a statistically significant difference in favor of sarilumab compared with adalimumab (–3.25 vs. –2.22, respectively; P < 0.0001). DAS28-ESR is a measure of disease activity in RA that includes the evaluation of 28 joints in the body for tenderness and swelling, a general health assessment, and the ESR, a laboratory measure for inflammation.

The study also met clinically important secondary endpoints, including improvements in the signs and symptoms of RA, as measured by a 20% improvement in the American College of Rheumatology criteria (ACR20) (72% for sarilumab compared with 58% for adalimumab; P < 0.01).

Additional positive secondary endpoints included ACR50 and ACR70 responses, and improvement in physical function, as measured by the Health Assessment Questionnaire– Disability Index (HAQ-DI). Sarilumab was superior to adalimumab for all of these measures (P < 0.01).

The incidence of adverse events (64% for both groups), serious adverse events (5% for sarilumab versus 7% for adalimumab), infections (29% versus 28%), and serious infections (1% for both groups) were generally similar between groups. Neutropenia, which was not associated with infections, was more common with sarilumab than than with adalimumab (14% versus 1%). Injection-site erythema was also more common with sarilumab (8% versus 3%).

In January, Regeneron and Sanofi announced that the FDA had accepted for review the biologics license application for sarilumab, with a target action date of October 30, 2016. The application was supported by 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 III program. The outcomes of the SARIL-RA-MONARCH trial are not part of the ongoing FDA review.

Source: Regeneron Pharmaceuticals; March 11, 2016.

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