Phase III SARIL-RA-MONARCH trial of SAR 153191 (sarilumab) meets primary endpoint and is superior to Humira (adalimumab) for rheumatoid arthritis- Sanofi/Regeneron

Sanofi and Regeneron Pharmaceuticals announced that a Phase III monotherapy study met its primary endpoint demonstrating that SAR 153191 (sarilumab) was superior to adalimumab (marketed by AbbVie as Humira) in improving signs and symptoms in patients with active rheumatoid arthritis (RA) at Week 24. The study, called SARIL-RA-MONARCH, also met important secondary endpoints including other measures assessing improvements in signs and symptoms of RA and physical function. Sarilumab is an investigational human IL-6 receptor antibody.

The SARIL-RA-MONARCH study enrolled 369 adult patients with active RA who were inadequate responders to, intolerant of, or inappropriate candidates for methotrexate (MTX). Patients were randomized to receive either subcutaneous sarilumab monotherapy (200 mg every 2 weeks) or adalimumab monotherapy (40 mg every 2 weeks); patients who did not respond adequately to adalimumab could increase to weekly dosing. The primary endpoint was change from baseline in DAS28-ESR at 24 weeks, which demonstrated a statistically significant difference in favour of sarilumab (-3.25 for sarilumab compared to -2.22 for adalimumab). The study also met clinically important secondary endpoints including improvements in signs and symptoms of RA as measured by patients achieving a 20% improvement in the American College of Rheumatology (ACR) criteria (72% for sarilumab vs. 58% for adalimumab, p <0.01). Additional positive secondary endpoints included ACR50 and ACR70 response, and improvement in physical function, as measured by the Health Assessment Questionnaire – Disability Index (HAQ-DI) as compared to adalimumab. DAS28-ESR is a measure of disease activity in RA, which includes the evaluation of 28 joints in the body for tenderness and swelling, a general health assessment, and ESR, a laboratory measure for inflammation.

The incidence of adverse events (64% for both groups), serious adverse events (5% for sarilumab vs. 7% for adalimumab), infections (29% for sarilumab vs. 28% for adalimumab), and serious infections (1% for both groups) were generally similar between groups. Neutropenia, which was not associated with infections, was more common with sarilumab (14% for sarilumab vs. 1% for adalimumab), as has been seen in previous studies with IL-6 inhibitors.

Comment: The FDA has accepted for review the BLA for sarilumab for the treatment of patients with active, moderate-to-severe rheumatoid arthritis. The PDUFA target action date is 30 October 2016.