Sanofi and Regeneron Pharmaceuticals Inc. announced results from Phase 2b trials in rheumatoid arthritis (RA) and ankylosing spondylitis (AS) with sarilumab (REGN88/SAR153191), a novel, high-affinity, subcutaneously administered, fully-human antibody targeting the interleukin-6 receptor (IL-6R).
The Phase 2b Mobility trial in rheumatoid arthritis demonstrated that patients treated with sarilumab in combination with a standard RA treatment, methotrexate (MTX), achieved a clinically meaningful improvement in signs and symptoms of moderate-to-severe RA compared to patients treated with MTX alone.
The Mobility study is a 306-patient, dose-ranging, multinational, randomized, multi-arm, double-blind, placebo-controlled study, that compared five different dose regimens of sarilumab in combination with MTX to placebo plus MTX. The primary endpoint of the study was the proportion of patients achieving at least a 20% improvement in RA symptoms (ACR20) after 12 weeks.
In the Mobility trial, there was a dose response observed in patients receiving sarilumab in combination with MTX. An ACR20 response after 12 weeks was seen in 49% of patients receiving the lowest sarilumab dose regimen and 72% of patients receiving the highest dose regimen compared to 46.2% of patients receiving placebo and MTX.
The most common adverse events reported more frequently in active-treatment arms included infections (non-serious), neutropenia, and liver-function test abnormalities. The types and frequencies of adverse events were consistent with those previously reported with IL-6 inhibition. The incidence of serious adverse events among the five sarilumab treatment groups and the placebo group were comparable.
Sarilumab also demonstrated significant benefit compared to placebo in secondary endpoints, including ACR 50, ACR 70, and DAS 28 scores, additional measures of clinical activity used in RA trials.
“Following these Phase 2b results in rheumatoid arthritis, the companies are currently discussing the dose(s) of sarilumab to advance into the Phase 3 portion of the Mobility trial,” says Elias Zerhouni, president, global research and development of Sanofi.
In the Phase 2b ALIGN trial in ankylosing spondylitis (AS), sarilumab did not demonstrate clinically meaningful improvements in signs and symptoms of active AS compared to placebo in patients who had inadequate response to NSAIDs. Sarilumab was generally well tolerated.
Release Date: July 12, 2011
Filed Under: Drug Discovery