Novartis-Partnered DARPin Antiviral Ensovibep Fails in Hospitalized COVID-19 Patients in ACTIV-3 Trial
Molecular Partners
Clinical-Stage Biopharmaceutical Company
Novartis
Drug Development and Manufacturing
National Institutes of Health
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Another drug fails in the ACTIV-3 clinical trial. In the COVID-19 study sponsored by the National Institutes of Health (NIH), the novel multispecific antiviral DARPin protein therapy ensovibep, developed by Molecular Partners in collaboration with Novartis, did not pass the test, leaving its hopes resting on a separate clinical trial for non-hospitalized patients.
NIH launched the ACTIV-3 trial to evaluate the efficacy of SARS-CoV-2 monoclonal antibodies and other therapies in hospitalized COVID-19 patients. Sub-studies on antibody drugs from Brii Biosciences, Eli Lilly, and GlaxoSmithKline-Vir Biotechnology have all failed, reinforcing the impression that antiviral antibody drugs targeting the virus itself are ineffective for hospitalized COVID-19 patients.
Molecular Partners has advanced ensovibep to phase 3 studies, hoping that its differences from antibody therapies will help achieve better outcomes. Ensovibep is a unique trispecific DARPin protein therapy with synergistic target binding capabilities and a molecular size much smaller than monoclonal antibodies. The molecule is designed to bind to three parts of the viral receptor-binding domain, which can enhance potency and prevent the virus from escaping through mutations. Mutations might limit the effectiveness of single-target antibodies.
However, whatever the advantages of ensovibep, they had no impact on the outcome of the ACTIV-3 study. Like previous molecules, ensovibep failed to pass the planned futility analysis, leading to the recommendation to halt enrollment in this sub-study. As a result, Molecular Partners' stock price plummeted by 37%.
Molecular Partners CEO Patrick Amstutz said in a statement that the failure of a series of drugs in ACTIV-3 "may be due to the multi-system inflammatory component of late-stage COVID-19 disease. By the time patients are hospitalized, the inflammatory component may be more important than the virus itself, making anti-inflammatory drugs like Actemra more effective than anti-SARS-CoV-2 antibodies."
In October 2020, Novartis and Molecular Partners reached a collaboration to develop two DARPin protein therapies for COVID-19, including ensovibep. The two parties still have the opportunity to demonstrate the efficacy of ensovibep in non-hospitalized patients. The Phase 2b portion of its clinical trial will provide the most critical data early next year. Molecular Partners has divided the trial into two parts: Phase 2 aims to show a reduction in viral load, while Phase 3 will evaluate hospitalization and mortality.
Reference Source: Novartis-partnered DARPin flames out in COVID-19 study, sending Molecular Partners' stock into nosedive
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