Anna Holmes, Kristin Narayan, Ilker Yalcin, Leijun Hu, Mark A Wingertzahn
Following a similar approach to prevention, immunobridging was demonstrated for pemivibart for the treatment of COVID-19, suggesting substantial antiviral activity. This development methodology provides a roadmap for accelerating novel COVID-19 treatment options amid a changing variant landscape.
BACKGROUND: Multiple SARS-CoV-2 receptor-binding domain-directed monoclonal antibodies (mAbs) have demonstrated substantial efficacy for the treatment of COVID-19. However, rapid virus evolution challenges traditional development pathways, as nonsusceptible variants can outpace development and regulatory review. Fortunately, mAb antiviral activity across variants can be measured via clinical serum virus-neutralizing antibody titers that correlate to clinical outcomes from historical mAbs and serve as surrogate biomarkers for efficacy. Analytic immunobridging facilitates rapid assessment of novel mAb efficacy. Immunobridging supported the Emergency Use Authorization of pemivibart, a mAb targeted to the spike protein of SARS-CoV-2 for the prevention of COVID-19 in certain patients with immune compromise. We applied a similar framework to evaluate pemivibart for the treatment of acute COVID-19.
METHODS: Complementary methods included the following: (1) strict immunobridging of neutralizing antibody titers of pemivibart to its parent molecule adintrevimab, (2) benchmarking comparison of pemivibart to historical mAbs with demonstrated efficacy in COVID-19 treatment, and (3) dose-response analysis of pemivibart vs comparator mAbs based on a meta-analysis.
RESULTS: Pemivibart demonstrated strict immunobridging to adintrevimab from 4 to >14 days across the variants analyzed. Neutralizing titers of pemivibart were 4- to 12-fold higher than titers for sotrovimab and less than titers for other historical intravenously administered mAbs throughout a 14-day analysis period. Dose-response analysis predicted pemivibart to have equivalent efficacy to all comparators.
CONCLUSIONS: Following a similar approach to prevention, immunobridging was demonstrated for pemivibart for the treatment of COVID-19, suggesting substantial antiviral activity. This development methodology provides a roadmap for accelerating novel COVID-19 treatment options amid a changing variant landscape.