Sarilumab Gets Nod from FDA for RA

May 24, 2017

The IL-6 inhibitor offers a monotherapy option for hard-to-treat rheumatoid arthritis cases.

The Food and Drug Administration (FDA) has approved sarilumab (Kevzara/Sanofi and Regeneron Pharmaceuticals, Inc.) for adults with moderate to severe active rheumatoid arthritis who have had an inadequate response or intolerance to one or more disease modifying antirheumatic drugs (DMARDs). 

“Sarilumab works differently from the most commonly used biologics, such as those in the anti-TNF class, and is a welcome new option for patients and their physicians," said Alan Kivitz, M.D., in a written statement provided by Sanofi and Regeneron Pharmaceuticals, Inc. Dr. Kivitz is founder and medical director of the Altoona Center for Clinical Research and Altoona Arthritis and Osteoporosis Center, and an investigator in the global SARIL-RA clinical program for sarilumab.

“Some patients may spend years cycling through different treatments without achieving treatment goals,” he said. Switching between biologics with different mechanisms of action is common practice in patients who have had an inadequate response to therapy or who have experienced serious adverse events.

Sarilumab, a human monoclonal antibody that targets the IL-6 receptor, is recommended once every two weeks given as a subcutaneous injection of 200 mg. The dosage can be reduced from 200 mg to 150 mg once every two weeks, as needed. It may be used as monotherapy or in combination with MTX or other conventional DMARDs.

Clinical trials of sarilumab

The approval of sarilumab was based on data two from two phase three trials - TARGET and MOBILITY - of 2,900 adults with moderate to severe active rheumatoid arthritis who had an inadequate response to previous treatments.

In MOBILITY, the combination of sarilumab and methotrexate reduced signs and symptoms, improved physical function, and demonstrated significantly less radiographic progression of structural damage, as compared to placebo plus methotrexate. At 24 weeks, 66 percent of patients receiving sarilumab 200 mg with methotrexate achieved ACR20 as compared to 58 percent on sarilumab 150 mg and 33 percent on placebo.

In the TARGET study, the combination of sarilumab plus a DMARD reduced signs and symptoms and improved physical function, compared to placebo and a DMARD. At 24 weeks, 61 percent of patients treated with sarilumab 200 mg plus a DMARD achieved ACR20 as compared to 55 percent on sarilumab 150 mg and 34 percent on placebo.

In 2016, the MONARCH study showed that sarilumab monotherapy was superior to adalimumab monotherapy in rheumatoid arthritis patients who cannot tolerate or did not respond to methotrexate. Sarilumab monotherapy was shown to be superior to adalimumab monotherapy in reducing disease activity and in improving physical function in rheumatoid arthritis. But the rate of infections, serious adverse events and overall adverse events was similar between the two therapies. The ASCERTAIN trial presented at the annual meeting of the American College of Rheumatology in November 2015 previously showed similar rates of adverse events in patients treated with sarilumab as compared to tocilizumab.

These findings are important because while combination therapy has proven to be highly effective in patients, about 30 percent of rheumatoid arthritis patients “rely on biologics as monotherapy because they have an intolerance or contraindications to combination therapy,” Gerd Burmester, M.D., a rheumatologist with Charité-University Medicine in Berlin, told Rheumatology Network in December 2016.

Adverse reactions  [[{"type":"media","view_mode":"media_crop","fid":"59949","attributes":{"alt":"Kevzara (Sarilumab). Photo courtesy of ©Sanofi, Regeneron.","class":"media-image media-image-right","id":"media_crop_5842313759622","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"7556","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"font-size: 13.008px; float: right;","title":"Kevzara (Sarilumab). Photo courtesy of ©Sanofi, Regeneron.","typeof":"foaf:Image"}}]]

Patients treated with sarilumab are at increased risk of developing serious infections. The most common adverse reactions - occurring in 3 percent of patients treated with sarilumab-DMARD combination therapy - was neutropenia, increased alanine aminotransferase, injection site erythema, upper respiratory infections and urinary tract infections.

European Union

In April, the European Medicine Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) recommended the approval of sarilumab (Kevzara/Sanofi and Regeneron Pharmaceuticals, Inc.) for adults with moderate to severe active rheumatoid arthritis who cannot DMARDs. The European Union is expected to make a decision later this year.

Also, from Rheumatology Network:

Sarilumab as Safe as Tocilizumab in RA Drug Trial, November 16, 2015

Efficacy Lies in Both Sarilumab and Methotrexate in RA, November 10, 2015

Sarilumab Monotherapy for RA Superior in MONARCH, Dec. 8, 2016

References:

"Sanofi and Regeneron Announce FDA Approval of Kevzara® (sarilumab) for the Treatment of Moderately to Severely Active Rheumatoid Arthritis in Adult Patients," joint statement by Sanofi and Regeneron Pharmaceuticals, Inc. May 22, 2017.

Tim Blake,corresponding author Vijay Rao, Tahir Hashmi, et al. "The perplexity of prescribing and switching of biologic drugs in rheumatoid arthritis: a UK regional audit of practice," BMC Musculoskeletal Disorders. 2014; 15: 290. Published online 2014 Sep 2. DOI:  10.1186/1471-2474-15-290

 

x