An investigator-led Phase III trial comparing authorised monoclonal antibodies (mAbs) from Eli Lilly and Regeneron Pharmaceuticals to treat Covid-19 has recruited approximately 1,500 participants to date, said investigator Dr David Huang, professor of Critical Care Medicine and Emergency Medicine, University of Pittsburgh, Pennsylvania. While he did not elaborate on when the study may be completed, Huang said an interim analysis on the data collected from recruited participants is underway and should be publicly available soon.
The overarching goal of the study is to illustrate the yet-unexplored comparative efficacy of the mAb therapies, said Huang. Such data will be valuable to the clinical field, which is using them to treat Covid-19, he said. At present, there are three FDA authorised mAb therapies to treat mild-to-moderate Covid-19.
The comparative efficacy data is especially relevant in the context of emerging SARS-CoV-2 variants, and the interim analysis will include data on variants at the individual and population level, as well as the efficacy of mAbs against them, said Huang. An Emergency Use Authorisation (EUA) for Eli Lilly’s bamlanivimab monotherapy was revoked on 16 April after an increased number of SARS-CoV-2 variants were found to be resistant to the therapy. Enrolment into the bamlanivimab monotherapy arm was stopped once the FDA decision came through, said Huang. Many participant swab samples are not available or adequate, but an effort is being made to collect them to help analyse variant data, he added.
The sample size for the Phase III OPTIMISE-C19 study is not fixed and will evolve based on the pandemic, said Huang. It is an open-label trial, but the outcome assessors who conduct follow-up calls to check for number of days alive and free from hospitalisation at day 28—the trial’s primary endpoint—are blinded to the mAb assigned to each individual participant. Additionally, investigators are blinded to the aggregate outcome data until a statistical analysis is done (Huang et al., Trials, (2021)22, p. 363).
The study was designed in February when the US White House Covid-19 Response Team asked the University of Pittsburgh Medical Center to ensure the administration of mAbs, Huang said. At that point, investigators saw the opportunity to conduct a head-to-head comparison between the mAbs, he added. The federal government is providing the mAbs to the hospital system.
Eli Lilly’s bamlanivimab and etesevimab cocktail was authorised based on results from a Phase III study where the combination demonstrated a 70% reduction in hospitalisation or death at 29 days compared to placebo among 1,035 nonhospitalised participants, as per a 9 February release. Regeneron’s REGEN-COV cocktail (casirivimab with imdevimab) was initially authorised at a cumulative 2,400mg dose on 21 November 2020, but a 4 June 2021 update now allows a lower 1,200mg intravenous and subcutaneous dose. The REGEN-COV cocktail also reduced the risk of hospitalisation or death at 29 days by 70% with the 1,200mg dose and by 71%, with the 2,400mg dose, based on data from 4,567 participants from the Phase I/II/III study, as per a 17 May release.
In addition to the mAbs from Lilly and Regeneron, the study will also incorporate GlaxoSmithKline and Vir Biotechnology’s newly authorised VIR-7831 (sotrovimab) once the therapy is available through the hospital pharmacy, Huang said. The FDA granted an EUA to VIR-7831 to treat mild-to-moderate Covid-19 on 26 May.
Manasi Vaidya is a Associate Editor for Pharmaceutical Technology parent company GlobalData’s investigative journalism team. A version of this article originally appeared on the Insights module of GlobalData’s Pharmaceutical Intelligence Center. To access more articles like this, visit GlobalData.