Kevzara Wins FDA’s OK for Treatment of Rheumatoid Arthritis

Wholesale acquisition cost is $39,000 per year

The FDA has approved sarilumab (Kevzara, Regeneron/Sanofi) for the treatment of adults with moderately to severely active rheumatoid arthritis (RA) who have shown an inadequate response to or are intolerant of one or more disease-modifying antirheumatic drugs (DMARDs), such as methotrexate (MTX). Sarilumab is a human monoclonal antibody that binds to the interleukin-6 receptor (IL-6R), thereby inhibiting IL-6R–mediated signaling. IL-6 is a cytokine that can contribute to the inflammation associated with RA.

Sarilumab may be used as monotherapy or in combination with MTX or other conventional DMARDs. The recommended dosage of sarilumab is 200 mg once every two weeks given as a subcutaneous injection, which can be self-administered. The dosage can be reduced from 200 mg to 150 mg once every two weeks, as needed, to help manage certain neutropenia, thrombocytopenia, and liver-enzyme elevations.

The approval of sarilumab was based on data from approximately 2,900 adults with moderately to severely active RA who had shown inadequate response to previous treatment regimens. In two pivotal phase 3 trials, sarilumab plus background DMARDs demonstrated significant improvements.

In the MOBILITY trial, treatment with sarilumab plus MTX reduced the signs and symptoms of RA, improved physical function, and demonstrated significantly less radiographic progression of structural damage compared with placebo plus MTX.

  • At 24 weeks, patients treated with sarilumab plus MTX achieved a greater improvement in the primary endpoint of the signs and symptoms of RA, as measured by the proportion of patients achieving a 20% improvement in the American College of Rheumatology criteria (ACR20) (sarilumab 200 mg: 66%; sarilumab 150 mg: 58%; and placebo: 33%).
  • At 52 weeks, patients treated with sarilumab plus MTX demonstrated significantly less radiographic progression of structural damage, as measured by the change in the modified Total Sharp Score, a key endpoint (sarilumab 200 mg: 0.25; sarilumab 150 mg: 0.90; and placebo: 2.78).
  • At 16 weeks, patients treated with sarilumab plus MTX demonstrated greater improvement from baseline in physical function, as measured by the Health Assessment Questionnaire–Disability Index (HAQ-DI), a key endpoint (sarilumab 200 mg: –0.58; sarilumab 150 mg: –0.54; and placebo: –0.30).

In the TARGET trial, treatment with sarilumab plus DMARDs reduced the signs and symptoms of RA and improved physical function compared with placebo plus DMARDs.

  • At 24 weeks, patients treated with sarilumab plus DMARDs achieved a greater improvement in the primary endpoint of signs and symptoms, as measured by the proportion of patients achieving an ACR20 response (sarilumab 200 mg: 61%; Kevzara 150 mg: 56%; and placebo: 34%).
  • At 12 weeks, patients treated with sarilumab plus DMARDs demonstrated greater improvement from baseline in physical function, as measured by the HAQ-DI (sarilumab 200 mg: –0.49; sarilumab 150 mg: –0.50; and placebo: –0.29).

Patients treated with sarilumab are at increased risk of developing serious infections, which may lead to hospitalization or death. The most common adverse events associated with the two doses of sarilumab plus DMARDs compared with placebo plus DMARDs included neutropenia (7% and 10% vs. 0.2%, respectively); increased alanine aminotransferase (5% vs. 2%); injection-site erythema (4% and 5% vs. 0.9%), upper respiratory-tract infections (3% and 4% vs. 2%); and urinary-tract infections (3% vs. 2%).

The U.S. wholesale acquisition cost (WAC) of sarilumab is $39,000 per year for the 200-mg and 150-mg doses, which is approximately 30% lower than the WAC for the two most widely used tumor necrosis factor-alpha inhibitors. Actual costs to patients, payers, and health systems are anticipated to be lower as the WAC does not reflect discounts, rebates, or copay support.

Source: Regeneron; May 22, 2017.