Sanofi and Regeneron today trumpeted successful results of the first Phase III trial for their rheumatoid arthritis (RA) drug candidate sarilumab, saying that the first fully human monoclonal antibody directed against the interleukin-6 receptor (IL-6R) in combination with methotrexate (MTX) therapy improved disease signs and symptoms as well as physical functions while inhibiting progression of joint damage in adults with RA who saw little improvement through MTX therapy alone.
Sarilumab met all three primary endpoints of the 52-week SARIL-RA-MOBILITY Phase III trial by demonstrating clinically relevant and statistically significant improvements compared to the placebo group in the two groups treated with the drug candidate. The trial enrolled about 1,200 patients with active, moderate-to-severe rheumatoid arthritis who were inadequate responders to MTX therapy.
Of patients treated with the 200 mg dose of sarilumab plus MTX, 66% saw improvement in signs and symptoms of RA at 24 weeks, as measured by the American College of Rheumatology score of at-least 20% improvement. The percentage dipped to 58% of sarilumab 150 mg dose patients, and 33% of placebo patients.
Sarilumab 200 mg patients showed the least progression of structural damage after 52 weeks, registering a 0.25 change in the modified Van der Heijde total Sharp score. That contrasts with scores of 0.90 in patients taking sarilumab 150 mg, and 2.78 in the placebo group.
In addition, sarilumab 200 mg patients showed improvement in physical function, as measured by change from baseline in the Health Assessment Question-Disability at week 16. However, the companies did not quantify those results in their announcement. Sanofi and Regeneron said additional analyses of efficacy and safety data from SARIL-RA-MOBILITY will be presented “at a future medical conference.”
“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,” Tanya M. Momtahen, Sanofi’s sarilumab global project head, said in a statement.
Sarilumab—known as SAR153191 and REGN88—blocks the binding of IL-6 to its receptor and interrupts the resultant cytokine-mediated inflammatory signaling characteristic of RA. Sarilumab was developed using Regeneron's VelocImmune® antibody technology.
The positive results continue what has been mostly strong success in clinical trials for the partners, whose development collaborations include alirocumab (REGN727), dupilumab (REGN668), and enoticumab (REGN421). Alirocumab is a PCSK9 antibody being evaluated for its ability to manage LDL cholesterol, including in people who do not get to their target LDL levels using statin medicines alone. Dupilumab is an antibody to the receptors for interleukin-4 and interleukin-13 under evaluation in atopic dermatitis and eosinophilic asthma. Enoticumab is a fully human monoclonal antibody to delta-like ligand-4 (Dll4) now in Phase I study for advanced malignancies.
On its own, however, Sanofi’s R&D efforts have shown more mixed results, with the pharma giant earlier this month ending development of cancer drug candidate fedratinib (SAR302503) after it was placed on clinical hold by the FDA following reports that some patients in clinical trials developed symptoms consistent with Wernicke’s encephalopathy. Another cancer compound, iniparib, had its development halted earlier this year after a disappointing Phase III trial.