Sanofi and Regeneron got EC approval of Kevzara® (sarilumab) in combo with MTX to treat adult patients with moderately to severely active RA

Sanofi and Regeneron Pharmaceuticals announced that the European Commission (EC) has granted marketing authorization 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.

RA affects approximately 2.9 million people in Europe alone. In RA, the immune system attacks the tissues of the joints, causing inflammation, joint pain, swelling, stiffness, fatigue, and eventually joint damage and disability. RA is most common in those aged 35-50 years old.

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. 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 program 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.

At 24 weeks, patients treated with Kevzara demonstrated greater reduction in disease activity as measured by change from baseline in the Disease Activity Score with 28 joint count and erythrocyte sedimentation rate (DAS28-ESR), the primary endpoint of the study (Kevzara, -3.28; adalimumab, -2.20)

At 24 weeks, patients treated with Kevzara demonstrated greater improvement from baseline in physical function as measured by the Health Assessment Questionnaire – Disability Index (HAQ-DI), a secondary endpoint of the study (Kevzara, -0.61; adalimumab, -0.43)

At 24 weeks, patients treated with Kevzara achieved higher rates of DAS28-ESR remission (score<2.6), a secondary endpoint of the study (Kevzara, 26.6%; adalimumab, 7.0%)

At 24 weeks, patients treated with Kevzara demonstrated a greater improvement in signs and symptoms of RA as measured by the proportion of patients achieving a 20 percent improvement in the ACR criteria (ACR20) (Kevzara, 71.7%; adalimumab, 58.4%; p=0.0074). The proportion of patients achieving ACR50 was also higher with Kevzara (Kevzara, 45.7%; adalimumab, 29.7%; p=0.0017) as well as for ACR70 (Kevzara, 23.4%; adalimumab, 11.9%; p=0.0036). ACR20, ACR50, and ACR70 response at week 24 were secondary endpoints of the study.

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 percent 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. Detailed results from the MOBILITY and TARGET studies are available in the Kevzara (sarilumab) FDA approval press release here.

The recommended dose of Kevzara is 200 mg once every 2 weeks administered as a subcutaneous injection with a prefilled syringe or prefilled pen.1 Reduction of dose from 200 mg once every weeks to 150 mg once every 2 weeks is recommended to help manage certain laboratory abnormalities (neutropenia, thrombocytopenia, and liver enzyme elevations).

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