Oral bemnifosbuvir (AT-527) vs placebo in patients with mild-to-moderate COVID-19 in an outpatient setting (MORNINGSKY)
Arantxa Horga, Rebecca Saenz, Gürdal Yilmaz, Abraham Simón-Campos, Keith Pietropaolo, William J Stubbings, Neil Collinson, Laura Ishak, Barbara Zrinscak, Bruce Belanger, Catherine Granier, Kai Lin, Aeron C hurt, Xiao-Jian Zhou, Steffen Wildum, Janet Hammond
Future Virology, doi:10.2217/fvl-2023-0115
Aim: This phase III study assessed the efficacy/safety/antiviral activity/pharmacokinetics of bemnifosbuvir, a novel, oral nucleotide analog to treat COVID-19. Patients & methods: Outpatient adults/adolescents with mild-to-moderate COVID-19 were randomized 2:1 to bemnifosbuvir/placebo. Time to symptom alleviation/improvement (primary outcome), risk of hospitalization/death, viral load and safety were evaluated. Results: Although the study was discontinued prematurely and did not meet its primary end point, bemnifosbuvir treatment resulted in fewer hospitalizations (71% relative risk reduction), COVID-19related medically attended hospital visits, and COVID-19-related complications compared with placebo. No reduction in viral load was observed. The proportion of patients with adverse events was similar; no deaths occurred. Conclusion: Bemnifosbuvir showed hospitalization reduction in patients with variable disease progression risk and was well tolerated. Clinical Trial Registration: NCT04889040 (ClinicalTrials.gov). Tweetable abstract: #Bemnifosbuvir is a novel, oral, nonmutagenic, nonteratogenic nucleotide analog with low potential for drug-drug interactions or resistance. Bemnifosbuvir showed a 71% reduction in hospitalization for #COVID-19 despite no symptom alleviation/viral load reduction differences. @ateapharma
Bemnifosbuvir
Summary points • Hospitalization due to COVID-19 has placed a significant burden on healthcare systems. With the advent of new SARS-CoV-2 variants, vaccines and other treatment approaches have shown diminished efficacy. As the pandemic continues to evolve, safe, effective, direct-acting and convenient antiviral agents with broad utility are needed. • Bemnifosbuvir is an oral, antiviral guanosine analog that inhibits viral RNA polymerase via a dual mechanism of action. • This phase III study of bemnifosbuvir was terminated early, enrolling only 216 of the planned 1386 patients. It did not achieve its primary end point, with patients who received bemnifosbuvir experiencing longer median time to symptom alleviation/improvement than those who received placebo. • Compared with those in the placebo group, patients who received bemnifosbuvir experienced fewer hospitalizations, with risk reduction for all evaluable patients (71%) and for those aged >40 years (82%). • Bemnifosbuvir treatment also led to fewer COVID-19-related medically attended hospital visits and COVID-19-related complications. • Bemnifosbuvir was well tolerated; most adverse events were mild to moderate, and no deaths occurred. • No difference in viral load was observed between the bemnifosbuvir and placebo groups. • With its dual mechanism of action, in vitro activity against all reported SARS-CoV-2 strains, favorable safety profile, and low potential for drug-drug interactions,..
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