Immunobridging Analysis of Pemivibart for the Treatment of COVID-19 – A Therapeutic Gap for the Immune Compromised Remains

Abstract Background Multiple SARS-CoV-2 RBD-directed mAbs demonstrated substantial efficacy for treatment of COVID-19. However, rapid virus evolution challenges traditional development pathways, as non-susceptible 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 demonstrated 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 prevention of COVID-19 in certain immunocompromised patients. We applied a similar framework to evaluate pemivibart for the treatment of acute COVID-19. Methods Complementary methods included: 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 to comparator mAbs based on a meta-analysis. Results Pemivibart demonstrated strict immunobridging to adintrevimab from 4 to >14 days across variants analyzed. Neutralizing titers of pemivibart were 4-12-fold higher than titers for sotrovimab and less than titers for other historical IV-administered mAbs throughout a 14-day analysis period. Dose-response analysis predicted pemivibart to have equivalent efficacy to all comparators. Conclusion 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 road map for accelerating novel COVID-19 treatment options amid a changing variant landscape.