EU approval for Regeneron and Sanofi’s rheumatoid arthritis drug

The European Commission (EC) has granted marketing authorisation for Regeneron and Sanofi’s 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.

Monoclonal antibody

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. Kevzara was developed using Regeneron’s proprietary VelocImmune technology that yields optimised fully-human antibodies.

"RA is a difficult-to-treat, lifelong disease and many healthcare providers are challenged with finding a treatment that works for their patients," said Elias Zerhouni MD, President, Global R&D, Sanofi. "Kevzara works differently from some of the other most commonly used biologics, and its approval is good news for the many patients where a high unmet need remains."

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.

"We are pleased to bring Kevzara to European patients who may not be responding to the most commonly used biologics such as TNF inhibitors, or who may be seeking an effective monotherapy to reach their treatment goals," said George Yancopoulos, MD, PhD, Founding Scientist, President, and Chief Scientific Officer, Regeneron. "This approval was made possible through the hard work of our innovative scientists, as well as thousands of dedicated investigators and patients around the world who participated in the SARIL-RA clinical trial program."

Supporting data

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; p less than 0.0001)

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; p=0.0036)

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%; p less than 0.0001)

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% for the Kevzara 200 mg dose and 68% 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.

Global approval

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

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