Self-Replicating mRNA Vaccine for COVID Prevention

Europe’s Committee for Medicinal Products for Human Use (CHMP) recommended granting marketing authorization for two drugs for preventing COVID-19: a monoclonal antibody called Kavigale (sipavibart) and a self-amplifying mRNA vaccine known as Kostaive (zapomeran). The recommendations are now in line for approval by the European Commission.

The active ingredient in Kavigale is sipavibart, which is an immunoglobulin, antiviral monoclonal antibody that provides passive immunization against SARS-CoV-2 by binding its spike protein receptor binding domain.

Kostaive’s active substance is zapomeran, a self-replicating mRNA that encodes the SARS-CoV-2 spike protein. It makes more copies of itself once inside host cells following intramuscular injection. The cells can then make copies of the spike protein. This induces the production of neutralizing antibodies and a cellular immune response to target the spike protein, thus protecting against COVID-19. 

Kavigale

The recommendation for Kavigale comes after results from AstraZeneca’s SUPERNOVA phase 3 trial. The trial compared the efficacy of sipavibart with control (tixagevimab/cilgavimab or placebo) for reducing the risk for symptomatic COVID-19 among immunocompromised patients aged 12 or older from multiple SARS-CoV-2 strains. 

Sipavibart ultimately outperformed both tixagevimab/cilgavimab and the placebo. The greatest reductions in symptomatic disease occurred for non-F456L mutation‒containing SARS-CoV-2 variants. The most common side effects of sipavibart were injection- and infusion-site reactions.

Kavigale will be made available as a 300 mg solution for injection or infusion. It is indicated to prevent COVID-19 in adults and adolescents aged 12 or older who weigh at least 40 kg and who are immunocompromised because of either a medical condition or immunosuppressive treatments. 

The medication should be used in accordance with official recommendations and information on the drug’s activity against current variants. 

Kostaive

The CHMPS’s recommendation of Kostaive comes after results from a study in which adults received either two doses of zapomeran or a placebo. Zapomeran led to greater reductions in the proportion of patients who developed symptomatic COVID-19 between 1 week and 3 months after the second dose. Another, smaller study also found that zapomeran is effective as a heterologous booster vaccine.

The most common side effects from zapomeran included injection-site reactions, arthralgia, myalgia, headache, dizziness, fatigue, chills, and pyrexia. 

Kostaive will be made available as a powder for dispersion for injection and should be used according to official recommendations. The vaccine is indicated for active immunization to prevent COVID-19 caused by SARS-CoV-2 in individuals aged 18 years or older. 

Detailed recommendations for both Kavigale and Kostaive will be described in the summary of product characteristics, which will be published following marketing authorization by the European Commission. 

Annie Lennon is a medical journalist. Her writing appears on Medscape, Medical News Today, and Psych Central, among other outlets.