Sanofi and Regeneron announce EC approval of Kevzara (sarilumab)

Sanofi and Regeneron Pharmaceuticals, announce that the European Commission (EC) has granted marketing authorisation for Kevzara (sarilumab) in combination with methotrexate (MTX) for the treatment of moderately to severely active rheumatoid arthritis (RA) in adult patients who have responded inadequately to – or who are intolerant to – one or more disease modifying anti-rheumatic drugs (DMARDs), such as MTX. Kevzara may be used as monotherapy in case of intolerance to MTX or when treatment with methotrexate is inappropriate.

Kevzara is a human monoclonal antibody that binds to the interleukin-6 receptor (IL-6R) and blocks pro-inflammatory IL-6 mediated signaling. Elevated levels of IL-6 are found in the synovial fluid of patients with RA and play an important role in both the pathologic inflammation and joint destruction which are hallmarks of RA.

The EC approval is based upon receipt of a positive opinion by European Medicine Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP), which evaluated results from seven Phase 3 trials in the global SARIL-RA clinical development program. Reportedly, these studies incorporate data from more than 3,300 adults with moderately to severely active RA who have had an inadequate response or intolerance to one or more biologic or non-biologic DMARDs.

The programme includes the Phase 3 MONARCH study, in which treatment with Kevzara 200 mg monotherapy was superior to adalimumab 40 mg (marketed by AbbVie as HUMIRA) monotherapy in reducing disease activity and improving physical function, with more patients achieving clinical remission over 24 weeks.

In the Phase 3 MOBILITY study, treatment with Kevzara plus MTX reduced signs and symptoms, improved physical function, and at week 52, inhibited the progression of structural damage by 91 percent for the Kevzara 200 mg dose and 68 per cent for the Kevzara 150 mg dose, compared to placebo plus MTX. In the Phase 3 TARGET study, treatment with Kevzara plus DMARD reduced signs and symptoms and improved physical function, compared to placebo plus DMARD.

The recommended dose of Kevzara is 200 mg once every two weeks administered as a subcutaneous injection with a prefilled syringe or prefilled pen. Reduction of dose from 200 mg once every two weeks to 150 mg once every two weeks is recommended to help manage certain laboratory abnormalities (neutropenia, thrombocytopenia, and liver enzyme elevations).

The most frequent adverse reactions observed with Kevzara in clinical studies were neutropenia, increased alanine aminotransferase, injection site erythema, upper respiratory infections, and urinary tract infections. The most common serious adverse reactions were infections. Treatment with Kevzara should be withheld in patients who develop a serious infection until the infection is controlled. Initiating treatment with Kevzara is not recommended in patients with a low neutrophil count, i.e., absolute neutrophil count (ANC) < 2 x 109/L and in patients with a platelet count below 150 x 103/μL.

Kevzara is also approved in the United States and Canada. The companies are seeking approvals in a number of other countries globally.