Sanofi and Regeneron share good news from Phase III rheumatoid arthritis trial

Monoclonal antibody sarilumab, designed to act against interleukin-6 receptor, meets all three co-primary endpoints

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PARIS and TARRYTOWN, N.Y.—November 22 brought news from Sanofi and Regeneron Pharmaceuticals Inc. of positive results on sarilumab—reportedly the first fully-human anti- interleukin-6 receptor (IL-6R) monoclonal antibody—in the SARIL-RA-MOBILITY Phase III clinical trial in adult patients with active rheumatoid arthritis who were inadequate responders to methotrexate therapy.
Specifically, the companies says that sarilumab treatment in combination with methotrexate improved disease signs and symptoms as well as physical function, and inhibited progression of joint damage.
Certainly Regeneron is glad to have such news to add to the momentum of its commercial success with the eye drug Eylea for wet age-related macular degeneration, but the positive results are particularly good news for Sanofi, which has seen some setbacks in its oncology research and development programs in recent months.
The 52-week SARIL-RA-MOBILITY Phase III trial enrolled approximately 1,200 patients with active, moderate-to-severe rheumatoid arthritis, and who were inadequate responders to methotrexate therapy. Patients were randomized to one of three subcutaneous treatment groups, all in combination with methotrexate and dosed every other week: sarilumab 200 mg, sarilumab 150 mg, or placebo.
According to Sanofi and Regeneron, both sarilumab groups showed clinically relevant and statistically significant improvements compared to the placebo group in all three co-primary endpoints. This included improvement in signs and symptoms of rheumatoid arthritis at 24 weeks, as measured by the American College of Rheumatology score, and the sarilumab 200 mg and sarilumab 150 mg showed 66-percent and 58-percent improvement, respectively, compared to 33-percent for placebo with methotrexate.
“IL-6 blockade is emerging as an important therapeutic approach for rheumatoid arthritis,” said Dr. Neil Graham, vice president of program direction, immunology and inflammation for Regeneron. “We are encouraged with these Phase III results, which demonstrated efficacy at both doses of sarilumab, each administered every other week.”
Participants also showed improvement in physical function, as measured by change from baseline in the Health Assessment Question-Disability at week 16 and inhibition of progression of structural damage at week 52, as measured by the change in the modified Van der Heijde total Sharp score (mTSS). The group receiving the 200 mg dose of sarilumab plus methotrexate had a reduction of approximately 90 percent in the radiographic progression assessed by the mTSS compared to the radiographic progression with placebo plus methotrexate at week 52.
“Irreversible joint damage can be a consequence for patients suffering from rheumatoid arthritis, and this is accompanied by reduced physical function in these patients,” noted Tanya M. Momtahen, sarilumab global project head for Sanofi. “This remains a major concern for rheumatoid arthritis patients.  We are encouraged by these Phase III results and the impact sarilumab demonstrated on inhibition of progression of structural damage assessed radiographically in this study.”
However, in the trial, researchers observed a higher incidence of treatment-emergent adverse events leading to withdrawal in the sarilumab treatment groups, among 13.9 percent of participants the 200 mg cohort and 12.5 percent of those in the 150 mg cohort, compared to only 4.7 percent of those taking placebo. Infections were the most frequently reported adverse events.
Among patients treated with sarilumab, a dose-dependent decrease in mean neutrophil counts also was observed, along with increases in mean low-density lipoprotein cholesterol and transaminases.
All of these safety findings were consistent with those observed in prior investigational studies with sarilumab, according to Sanofi and Regeron.  
Sarilumab, also known as REGN88/SAR153191, blocks the binding of IL-6 to its receptor, thus interrupting the resultant cytokine-mediated inflammatory signaling. The drug was developed using Regeneron's VelocImmune antibody technology.
Since 2007, Regeneron has collaborated with French pharma giant Sanofi to discover, develop, manufacture and commercialize fully human monoclonal antibodies utilizing the New York company’s VelociSuite set of technologies. In the first three years of the collaboration, five antibodies have entered clinical development, Regeneron notes on its website. The collaboration was expanded in 2009, setting an ambitious goal of advancing 20 to 30 additional antibodies into clinical development by 2017. Under the terms of the expanded collaboration, Sanofi has agreed to provide $160 million per year in research funding through 2017.
Sanofi has the exclusive option to co-develop each drug candidate in the collaboration portfolio. Development costs are to be shared between the two companies, with Sanofi funding development costs up front and Regeneron reimbursing half of the development costs from its share of future profits. Although Sanofi will take the lead in commercialization activities, Regeneron will have the right to co-promote all collaboration products worldwide. In the United States, profits will be shared equally, while outside the United States, profits will be split on a pre-determined sliding scale.

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