Regeneron, Sanofi initiates clinical trial in Kevzara to treat COVID-19

Regeneron Pharmaceuticals and Sanofi have started a clinical programme evaluating Kevzara (sarilumab) in patients hospitalized with severe coronavirus (COVID-19) infection.

Kevzara is a fully-human monoclonal antibody that inhibits the interleukin-6 (IL-6) pathway by binding and blocking the IL-6 receptor. IL-6 may play a role in driving the overactive inflammatory response in the lungs of patients who are severely or critically ill with COVID-19. The role of IL-6 is supported by preliminary data from a single-arm study in China using another IL-6 receptor antibody.

This US-based trial will begin at medical centers in New York, one of the epicenters of the US COVID-19 outbreak, and will assess the safety and efficacy of adding Kevzara to usual supportive care, compared to supportive care plus placebo. The multi-center, double-blind, phase 2/3 trial has an adaptive design with two parts and is anticipated to enroll up to 400 patients. The first part will recruit patients with severe COVID-19 infection across approximately 16 US sites, and will evaluate the impact of Kevzara on fever and patients’ need for supplemental oxygen. The second, larger part of the trial will evaluate the improvement in longer-term outcomes including preventing death and reducing the need for mechanical ventilation, supplemental oxygen and/or hospitalization.The use of Kevzara to treat the symptoms of COVID-19 is investigational and has not been fully evaluated by any regulatory authority.

This phase 2/3, randomized, double-blind, placebo-controlled trial uses an adaptive design to evaluate the safety and efficacy of Kevzara in adults hospitalized with serious complications from COVID-19. To enter the trial, patients must be hospitalized with laboratory-confirmed COVID-19 that is classified as severe or critical, or who are suffering from multi-organ dysfunction. All patients must have pneumonia and fever. After receiving the study dose, patients will be assessed for 60 days, or until hospital discharge or death.

In the phase 2 part of the trial, patients will be randomized 2:2:1 into three groups: Kevzara high dose, Kevzara low dose and placebo. The primary endpoint is reduction of fever and the secondary endpoint is decreased need for supplemental oxygen.

The phase 2 findings will be utilized in an adaptive manner to determine transition into phase 3, helping to determine the endpoints, patient numbers and doses. The second, larger part of the trial will evaluate the improvement in longer-term outcomes including preventing death and reducing the need for mechanical ventilation, supplemental oxygen and/or hospitalization.

If the trial continues with all three treatment arms to the end, it is expected to enroll approximately 400 patients, depending on the status of the COVID-19 outbreak and the proportion of patients with severe COVID-19 and high levels of IL-6.

Co-development of Kevzara

• Kevzara was jointly developed by Regeneron and Sanofi under a global collaboration agreement.
• In late 2019, Regeneron and Sanofi announced their intent to simplify the joint collaboration for Kevzara, which is expected to be finalized in the first quarter of 2020. The companies will continue to collaborate on COVID-19 and other related ARDS development, with Regeneron leading US-based work and Sanofi leading work outside of the US.
• Kevzara is a fully-human monoclonal antibody that was invented using Regeneron’s proprietary VelocImmune technology, which uses a unique genetically-humanized mouse to produce optimized fully human antibodies.

About Kevzara

• Kevzara is a fully-human monoclonal antibody.
• Kevzara binds specifically to the IL-6 receptor, and has been shown to inhibit IL-6-mediated signaling. IL-6 is a signaling protein produced in increased quantities in patients with rheumatoid arthritis and has been associated with disease activity, joint destruction and other systemic problems.
• It is also being investigated for its ability to reduce the overactive inflammatory immune response associated with COVID-19.