FDA Approves Regeneron and Sanofi Treatment for Rare Inflammatory Rheumatic Disease

Rare Daily Staff

The U.S. Food and Drug Administration has approved Regeneron Pharmaceuticals’ and Sanofi’s Kevzara for the treatment of polymyalgia rheumatica, an inflammatory rheumatic disease, in adult patients who have had an inadequate response to corticosteroids or who cannot tolerate corticosteroid taper.

Polymyalgia rheumatica (PMR) is a rare disorder that affects twice as many females as males. Affected individuals are usually over the age of 50 years. This disorder occurs at the rate of about 50 per 100,000 in people over 50 years of age.

PMR often initially presents with pain and stiffness around the neck, shoulder, and hip area and symptoms include fatigue, low-grade fever, and weight loss. Patients often experience flares during tapering of, or relapse after discontinuation of corticosteroid treatment. Patients with PMR report difficulty in carrying out everyday functions such as getting out of bed, standing up from a chair, or lifting their arms. PMR generally affects people who are 50 years and older.

“Polymyalgia rheumatica can be an incapacitating disease, causing painful disease flares in multiple parts of the body that leave people fatigued and unable to fully perform everyday activities. Corticosteroids have been the primary treatment to date, but many patients do not adequately respond to steroids or cannot be tapered off steroids, which puts such patients at risk of complications from long-term steroid therapy,” said George Yancopoulos, president and chief scientific officer at Regeneron. “With the approval of Kevzara for polymyalgia rheumatica, patients now have an FDA-approved treatment to help offer relief from the disabling symptoms of this disease and long-term dependance on steroids.”

The FDA evaluated the Kevzara application for PMR under Priority Review, which is granted to therapies that have the potential to provide significant improvements in the treatment, diagnosis, or prevention of serious conditions. Kevzara was previously approved for the treatment of moderately-to-severely active rheumatoid arthritis in adult patients who have had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs.

“Until now, people living with polymyalgia rheumatica have had limited treatment options for this serious rheumatic condition, which causes significant pain and discomfort,” said Bill Sibold, Executive Vice President, Head, Specialty Care at Sanofi. “The approval of Kevzara as the first and only biologic for polymyalgia rheumatica is a new option for patients and the healthcare professionals who treat them.”

The FDA approval for this additional indication for Kevzara is based on results from the SAPHYR phase 3 randomized clinical trial in patients with steroid resistant active PMR, who flared on ≥7.5 mg/day prednisone or equivalent during taper. In the trial, patients were randomized to receive either Kevzara 200 mg every two weeks along with a 14-week taper of corticosteroids; 1 patient randomized but not treated) or placebo every two weeks along with a 52-week corticosteroids taper. At 52 weeks, the trial met its primary endpoint with 28 percent of Kevzara-treated patients achieving sustained remission compared to 10 percent for placebo. Sustained remission was defined as being in disease remission by week 12, absence of disease flare, C-reactive protein normalization from weeks 12 to 52, and adherence to the corticosteroids taper protocol from weeks 12 to 52.

A sensitivity analysis removing acute phase reactants (measures of ongoing inflammation) maintained significance (proportion difference for Kevzara vs. placebo: 18 percent; 95 percent confidence interval: 3.1 to 32.6) and confirmed the primary outcome. In addition, an analysis of a secondary endpoint showed that the median cumulative corticosteroid dose was 777 mg for Kevzara, compared to 2044 mg for placebo.

The common adverse reactions occurring in ≥5 percent of patients treated with Kevzara were neutropenia (15 percent), leukopenia (7 percent), constipation (7 percent), rash pruritic (5 percent), myalgia (7 percent), fatigue (5 percent), and injection site pruritus (5 percent). Serious adverse reaction of neutropenia occurred in 2 patients (3 percent) in the Kevzara group compared to none in the placebo group. In both cases of neutropenia, the neutropenia resolved following permanent discontinuation of study drug. The most common adverse reactions that resulted in permanent discontinuation of therapy with Kevzara were neutropenia occurring in 3 patients (5 percent) and infection in 3 separate patients (5 percent).

Kevzara (sarilumab), which was invented using Regeneron’s proprietary VelocImmune technology, binds specifically to the IL-6 receptor and has been shown to inhibit IL-6-mediated signaling. IL-6 is an immune system protein produced in increased quantities in patients with rheumatoid arthritis and has been associated with disease activity, joint destruction, and other systemic problems. Sarilumab is being jointly developed by Regeneron and Sanofi under a global collaboration agreement.

Photo: George Yancopoulos, president and chief scientific officer at Regeneron