Sanofi/Regeneron’s biologic sarilumab has come out on top in a Phase III trial pitting its efficacy in improving the signs and symptoms of rheumatoid arthritis against that of AbbVie’s mega-blockbuster Humira, the world’s biggest selling drug with sales of more than $13 billion from across its various indications.

The Phase III SARIL-RA-MONARCH study enrolled 369 adult patients with active rheumatoid arthritis (RA) in whom treatment with methotrexate was either inadequate or not tolerated. Patients were randomised to receive either subcutaneous sarilumab monotherapy or adalimumab monotherapy.

The primary endpoint was change from baseline in DAS28-ESR - a disease activity score calculator 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 - which demonstrated a statistically significant difference in favour of sarilumab (-3.25 versus -2.22 for adalimumab) at 24 weeks.

“Clinically important” secondary endpoints - such as improvements in signs and symptoms of RA as measured by patients achieving a 20 percent improvement in the American College of Rheumatology (ACR 20) criteria (72 percent versus 58 percent for adalimumab) - were also met, the firms said. 

"This is the first time an IL-6 receptor blocker delivered subcutaneously has demonstrated superiority over adalimumab monotherapy in RA,” noted Janet van Adelsberg, senior director, Clinical Sciences, Immunology and Inflammation at Regeneron, commenting on the results. 

Similar safety profile

On the safety side, the incidence of adverse events (64 percent for both groups), serious adverse events (5 percent for sarilumab vs 7 percent for adalimumab), infections (29 percent for sarilumab vs. 28 percent for adalimumab), and serious infections (1 percent for both groups) were generally similar between groups. 

Neutropenia, which was not associated with infections, was more common with sarilumab (14 percent for sarilumab vs 1 percent for adalimumab), as has been seen in previous studies with IL-6 inhibitors. Injection site erythema (8 percent sarilumab vs 3 percent adalimumab) was also more common with sarilumab. 

Despite the availability of a wide range of treatment options, we believe that new therapies are needed to further address unmet needs of RA patients," said Simon Cooper, global project head, Immunology and Inflammation, Sanofi. "These data suggest that sarilumab, if approved, may be an option for patients unable to tolerate or take methotrexate, and we look forward to sharing further details at an upcoming medical congress."

But a spokesperson for AbbVie noted the study only evaluated signs and symptoms of RA with monotherapy treatment. "The current standard of care and routine clinical practice is the combination therapy of anti-TNFs and methotrexate, with the goal of preventing the progression of joint damage, a clinical measure where HUMIRA has set the standard".

US regulators are currently review an application to market sarilumab for patients with active, moderate-to-severe RA, which includes data showing significant improvement in signs and symptoms of RA at 24 weeks as measured by the ACR20 score, with: 61 percent in the sarilumab 200mg group; 56 percent in the sarilumab 150mg group; and 34 percent in the placebo group, all in combination with disease-modifying anti-rheumatic drugs.