FDA Approves Sarilumab for Adults With Polymyalgia Rheumatica

Sarilumab is a fully human monoclonal antibody indicated for patients with polymyalgia rheumatica who had an inadequate response to corticosteroids or are unable to tolerate corticosteroid taper.

The FDA has approved sarilumab (Kevzara; Regeneron Pharmaceuticals, Inc and Sanofi) for the treatment of adult patients with polymyalgia rheumatica (PMR) who had an inadequate response to corticosteroids (CS) or are unable to tolerate CS taper. Sarilumab, which was previously granted priority review for this indication, is a fully human monoclonal antibody that inhibits the interleukin-6 (IL-6) pathway by binding and blocking the IL-6 receptor, which inhibits IL-6-mediated signaling.

"[PMR] 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,” George D. Yancopoulos, MD, PhD, president and chief scientific officer at Regeneron, said in a press release. “With the approval of Kevzara for [PMR], 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 previously approved sarilumab for adult patients with moderately-to-severely active rheumatoid arthritis who had an inadequate response or intolerance to 1 or more disease-modifying antirheumatic drugs. PMR is an inflammatory rheumatic disease that frequently manifests with pain and stiffness around the neck, shoulder, and hips, with symptoms that include fatigue, low-grade fever, and weight loss.

Patients with PMR typically experience flares during the tapering of, or relapse after discontinuation of CS therapy. Patients often note difficulty in performing daily functions that affect quality of life, including getting out of bed, standing up, or lifting their arms. The condition generally impacts individuals aged 50 years and older.

The approval of sarilumab for PMR was based on findings from the phase 3 SAPHYR clinical trial among patients with steroid-resistant active PMR who flared on ≥7.5 mg/day prednisone or equivalent during taper. Patients were randomized to either sarilumab 200 mg every 2 weeks plus a 14-week taper of CS (n=60; 1 patient randomized but not treated) or placebo every 2 weeks plus a 52-week CS taper (n=58).

The trial met its primary endpoint at 52 weeks, with 28% of patients administered sarilumab achieving sustained remission vs 10% for placebo (p=0.0193). The trial investigators defined sustained remission as being in remission by week 12, absence of disease flare, C-reactive protein normalization from weeks 12 to 52, and adherence to the CS taper protocol from weeks 12 to 52.

The primary outcome was confirmed by a sensitivity analysis that removed measures of ongoing inflammation and maintained significance (proportion difference for sarilumab vs placebo: 18%; 95% confidence interval: 3.1 to 32.6). Further, the median cumulative CS dose was 777 mg for sarilumab vs 2044 mg for placebo, which was a secondary endpoint of the trial.

The most common adverse events (AEs) reported with sarilumab occurring in ≥5% of patients (n=59) were neutropenia (15%), leukopenia (7%), constipation (7%), rash pruritic (5%), myalgia (7%), fatigue (5%), and injection site pruritus (5%).

Neutropenia occurred in 2 patients (3%) in the sarilumab cohort vs zero in the placebo group (n=58). Both patients who developed neutropenia had a neutrophil count less than 500 per mm3 without any infections; neutropenia resolved following permanent discontinuation of sarilumab. The most common AEs resulting in permanent discontinuation of sarilumab other than neutropenia were infection in 3 separate patients (5%), including COVID-19 (n=1), intervertebral discitis (n=1), and pneumonia (n=1).

“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, in a press release. “The approval of Kevzara as the first and only biologic for polymyalgia rheumatica is a new option for patients and the health care professionals who treat them.”


Kevzara® (Sarilumab) Approved By FDA As First And Only Biologic Indicated For Patients With Polymyalgia Rheumatica. Regeneron. News release. https://investor.regeneron.com/news-releases/news-release-details/kevzarar-sarilumab-approved-fda-first-and-only-biologic. February 28, 2023.

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