Sanofi and Regeneron Pharmaceuticals, Inc. announced results from phase II b 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 II b Mobility trial in rheumatoid arthritis demonstrated that patients treated with sarilumab in combination with a standard RA treatment, methotrexate (MTX), achieved a significant and 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, multi-national, 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 per cent 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 49.0% of patients receiving the lowest sarilumab dose regimen and 72.0% of patients receiving the highest dose regimen compared to 46.2% of patients receiving placebo and MTX (p=0.02, corrected for multiplicity, for the highest sarilumab dose regimen). The most common adverse events (>5%) 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 encouraging phase II b results in RA, the companies are currently discussing the dose(s) of sarilumab to advance into the phase III portion of the Mobility trial,” said Elias Zerhouni, president, Global Research & Development, Sanofi.

“The Mobility results provide evidence that IL-6R blockade with sarilumab represents a promising new anti-inflammatory investigational therapy for reducing RA disease symptoms. We are very pleased that the first of our novel VelocImmune derived antibodies is poised to enter phase III development,” said George D Yancopoulos, MD, PhD, chief scientific officer of Regeneron and president of Regeneron Research Laboratories.

In the phase II b Align trial in Ankylosing Spondylitis (AS), sarilumab did not demonstrate significant and 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. The most common adverse events reported more frequently in active treatment arms included infections and neutropenia.

Sarilumab (REGN88/ SAR153191) is the first fully human monoclonal antibody directed against the alpha subunit of the IL-6 receptor complex (IL-6Ra). Sarilumab is a high affinity, sub-cutaneously delivered, specific inhibitor of IL-6 signalling. It blocks the binding of IL-6 to its receptor and interrupts the resultant cytokine-mediated inflammatory signalling cascade. Sarilumab was developed using Regeneron VelocImmune antibody technology.

The Mobility trial is a randomized, double-blind, placebo-controlled, multi-centre, two-part, dose ranging and confirmatory study with an operationally seamless design, evaluating efficacy and safety of sarilumab on top of MTX in patients with active RA who are inadequate responders to MTX therapy. The primary objective of part A of the dose ranging Mobility trial was to demonstrate that sarilumab on top of MTX is effective in reducing the signs and symptoms of RA at 12 weeks. The five doses tested were 100 milligrams (mg) and 150 mg every week and 100 mg, 150 mg and 200 mg every other week. The primary objective of part B of the Mobility trial will be to demonstrate that sarilumab on top of MTX is effective in reducing the signs and symptoms of RA at 24 weeks.

Rheumatoid Arthritis (RA) is a chronic systemic autoimmune disease affecting approximately 0.5%–1% of the global adult population. Abnormal immune response causes an inflamed, thickened synovium, the membrane that lines the joint. As synovitis expands, the inflammatory process can damage the bone and cartilage of the joint and the surrounding tissues. RA-related inflammation can involve the heart and the lung. In 10% of patients with RA the liver is affected. Complications of RA include anaemia and leucopenia.

At times RA can be very painful and affect a person's ability to carry out everyday tasks. Most people with RA experience periods when their symptoms worsen (flares or active disease) separated by periods in which the symptoms improve. Studies suggest that blockade of IL-6 signalling, one of several key cytokines involved in the inflammatory processes related to RA, may reduce inflammation of the joints, prevent long-term damage and relieve certain systemic effects of RA such as decreased haemoglobin, fatigue and osteoporosis.

The 300-patient Align trial is a randomized, double-blind, placebo-controlled, dose ranging study to evaluate the efficacy and safety of sarilumab in patients with AS who had an inadequate response to NSAIDs. The primary outcome measure of the trial was the percentage of patients who achieved a 20% improvement in AS International Working Group Criteria for improvement (ASAS20) at 12 weeks. The secondary endpoints included ASAS40 response, partial remission, and changes in disease activity, safety and tolerability. In the Align trial, the same dose regimens were tested as in part A of the Mobility trial.

Sanofi, a global and diversified healthcare leader, discovers, develops and distributes therapeutic solutions focused on patients’ needs. It has core strengths in the field of healthcare with seven growth platforms: diabetes solutions, human vaccines, innovative drugs, rare diseases, consumer healthcare, emerging markets and animal health.

Regeneron is a fully integrated biopharmaceutical company that discovers, develops, and commercializes medicines for the treatment of serious medical conditions.