USA-based biotech firm Regeneron and French global biopharma Sanofi this week announced dosing of the first patient in a phase 2/3 clinical trial of sarilumab (Kevzara) for treating patients hospitalised with serious complications of COVID-19. Initiated in Italy, Spain, Germany, France, Canada and Russia, the study parallels a similar trial launched in the USA in mid-March.
If successful, when added to supportive care, sarilumab may reduce the extreme inflammatory reaction in the lungs of patients with severe or critical COVID-19, reducing fever, lung congestion and the need for ventilators and supplementary oxygen, and reducing the risk of death.
Sarilumab is currently approved in Europe and the USA for treating moderate-to-severe rheumatoid arthritis (RA) refractive to other treatment. It works by blocking the interleukin-6 (IL-6) receptors on cells. This disrupts inflammatory signalling associated with severe inflammatory responses that include production of cytokines and recruitment of T-cells in RA. Evidence that the IL-6 pathway may be involved in COVID-19 inflammation comes from a single-arm study of another IL-6 blocker reported by researchers in China, which has since approved its use with supportive care for COVID-19.
The current phase II/III trials start with a 2:2:1 randomisation of high dose, low dose and placebo in a study with an adaptive design that will inform endpoints, dosing, and treatment arm composition and size in the transition to phase III. If the trial continues with all three arms to the end it will enrol about 300 patients.
“These trials will provide important data to determine whether Kevzara ameliorates the life-threatening complications of COVID-19 infections by counteracting the overactive inflammatory immune responses in the lungs when damaged by the virus. In these unprecedented times, we are deeply grateful for the daily collaboration with health authorities that is enabling us to conduct this clinical work so quickly,” John Reed MD, PhD, Sanofi’s global head of research and development, said in a statement.
Separately, Regeneron is developing antibodies targeting proteins unique to the SARS-CoV-2 virus. The firm’s researchers have isolated multiple antibodies from genetically modified mice infected with SARS-CoV-2 and from humans who have recovered from COVID-19. Several antibodies are now being tested to create an antibody “cocktail” with the greatest effectiveness against the virus.
The multi-antibody approach may help protect against multiple viral strains. If successful, the resulting treatment could prevent infection when injected before exposure to the virus, and may mitigate disease in those already infected. Regeneron hopes to have a treatment ready for human trials by the beginning of summer.
Sanofi is separately working on a vaccine that, if successful, could prevent COVID-19 in patients exposed to the SARS-CoV-2 coronavirus.
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