With sarilumab cruising toward a potential FDA approval this fall or earlier, drug developers Sanofi SA and Regeneron Pharmaceuticals Inc. reported that, at week 24, the interleukin-6 receptor antibody beat Humira (adalimumab, Abbvie Inc.) monotherapy on the study's primary endpoint, improving signs and symptoms in patients with active rheumatoid arthritis (RA).

While the data won't be incorporated into sarilumab's biologics license application, submitted to the FDA in January, Janet van Adelsberg, Regeneron's senior director of clinical sciences, immunology and inflammation, told BioWorld Today that "we think it's really important to provide information to physicians about what to do when their patient can't take methotrexate and yet they have really moderate to severe RA, they're at risk of long-term disability and, in the present moment, they're extremely uncomfortable."

The phase III trial, called Saril-RA-Monarch, included patients who either had inadequate responses to or aren't candidates for treatment with methotrexate, one of the most widely used and consistently effective disease-modifying antirheumatic drugs (DMARDs). It builds on data from earlier phase III trials of the therapy, including Saril-RA-Mobility and another trial, called Saril-RA-Target, for which results were announced in May 2015. (See BioWorld Today, May 22, 2015.)

In addition to meeting its primary endpoint, the Monarch trial also met its secondary endpoints, including other measures assessing improvements in signs and symptoms of RA and physical function. Full results will be presented at a future medical meeting.

Estimates by those who have studied methotrexate's real-world usage suggest that at least 30 percent of patients either aren't taking methotrexate with their biologic or don't fill their prescription for the drug due to its side effects, which can include dizziness, drowsiness, confusion and even seizures.

"We were extremely pleased with the results of the Monarch study, which shows that sarilumab looks like it could be a significant option for patients who can't take methotrexate, assuming the drug gets approved," said van Adelsberg.

Sarilumab has a PDUFA date of Oct. 30.

Monarch enrolled 369 adult patients with active RA who were inadequate responders to, intolerant of or inappropriate candidates for methotrexate. Patients were randomized to receive either subcutaneous sarilumab monotherapy (200 mg every two weeks) or adalimumab monotherapy (40 mg every two weeks). Patients who did not respond adequately to adalimumab could increase to weekly dosing.

The study's primary endpoint, evaluated at 24 weeks, was change from baseline in DAS28-ESR, a measure of disease activity in RA, 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. Patients demonstrated a statistically significant difference in favor of sarilumab (-3.25 for sarilumab compared to -2.22 for adalimumab, p < 0.0001).

The study also met secondary endpoints, including improvements in signs and symptoms of RA as measured by patients achieving a 20 percent improvement in the American College of Rheumatology (ACR) criteria (72 percent for sarilumab vs. 58 percent for adalimumab, p < 0.01). Additional positive secondary endpoints included ACR50 and ACR70 response, and improvement in physical function, as measured by the Health Assessment Questionnaire - Disability Index as compared to adalimumab (p < 0.01 for all measures).

Piper Jaffray analyst Edward Tenthoff wrote that his team sees "sarilumab's superiority to Humira as an important factor in determining ultimate market share." He said he expects the therapy to be approved by its PDUFA date and, despite the need for neutropenia signals to be monitored, believes that "sarilumab's efficacy and overall safety will allow it to penetrate the crowded RA space."

While the data were broadly heralded as a positive for Regeneron, Jefferies analyst Biren Amin pointed out that the trial's data appear similar to data reported with Roche AG's Actemra (tocilizumab) from its ADACTA trial, and are unlikely to drive differentiation vs. Actemra. Given the similarities, he wrote, "we think sarilumab's adoption will be driven by pricing/rebating."

In October 2103, Roche unit Genentech Inc. gained FDA approval to market Actemra for use in adults with moderately to severely active RA who have had an inadequate response to DMARDs. Roche started marketing Actemra for the treatment of severe, active and progressive RA in adults not previously treated with methotrexate in Europe in October 2014.

At least one other anti-IL-6 signal transduction modulator for RA is in development, according to Thomson Reuters Cortellis Clinical Trials Intelligence: ALX-0061, a program that includes two ongoing phase IIb studies in RA, is being developed by Abbvie and Ablynx NV. The program is part of an $840 million licensing deal the companies signed in 2013. Results of the studies are expected in the second half of 2016. (See BioWorld Today, Sept. 25, 2013.)

In addition to RA, Regeneron is also advancing sarilumab for the potential treatment of non-infectious uveitis. The company has preliminary data from a 16-week timepoint in a phase II study for that indication, but the year-long trial is ongoing.