Atea Pharmaceuticals, Inc. announced additional details on its clinical development plans for bemnifosbuvir for the treatment of COVID-19. Following meetings with the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) Emergency Task Force, Atea plans to initiate a global Phase 3 registrational clinical trial of bemnifosbuvir for the treatment of COVID-19 in the fourth quarter of 2022. The trial will evaluate bemnifosbuvir as both monotherapy and combination antiviral therapy in outpatients (non-hospitalized) with COVID-19 who are at the highest risk of disease progression, regardless of vaccination status.

Bemnifosbuvir is an investigational orally administered, non-mutagenic, non-teratogenic, direct-acting antiviral derived from AteaÆs purine nucleos(t)ide prodrug platform. Results from the late-stage MORNINGSKY trial showed a 71% reduction in hospitalization (secondary endpoint) with bemnifosbuvir versus placebo (p=0.047, unadjusted, exploratory) (n=207). In a subgroup analysis, patients > 40 years old had an 82% reduction in hospitalization.

Bemnifosbuvir targets SARS-CoV-2 RNA polymerase (nsp12), a highly conserved gene that is unlikely to change as the virus mutates and new variants continue to emerge. This gene is responsible for both replication and transcription of SARS-CoV-2. The inhibition of RNA polymerase has been shown in vitro to effectively block production of SARS-CoV-2. In addition, in vitro data confirm that bemnifosbuvir is active with similar efficacy against all variants of concern or interest that have been tested, suggesting antiviral activity against future variants. BemnifosbuvirÆs unique mechanism with dual targets is designed to create a high barrier to resistance.

The randomized, double-blind, placebo-controlled, global Phase 3 study will evaluate bemnifosbuvir or placebo administered concurrently with locally available standard of care (SOC). The study is designed to enroll at least 1,500 high-risk non-hospitalized patients with mild or moderate COVID-19. Patients will be randomized 1:1 to receive either bemnifosbuvir 550 mg twice-daily (BID) plus locally available SOC or placebo BID plus locally available SOC for five days.

This trial will include two populations derived from the type of SOC received. They include 1) ôSupportive care populationö (the patient does not qualify for an approved antiviral treatment or where antivirals are not locally available) which will assess bemnifosbuvir given as monotherapy (primary analysis) and 2) ôCombination antiviral populationö which will assess combination therapy if the SOC includes treatment with other compatible antiviral drugs against COVID-19 (secondary analysis). The primary endpoint of the study is all-cause hospitalization or death through Day 29 in the supportive care population in at least 1,300 patients.

Secondary endpoints in each patient population include: COVID-19 complications, medically attended visits, symptom rebound /relapse and viral load rebound. The patient population will consist of those at the highest risk for disease progression, including patients = 80 years old, patients = 65 years old with = one major risk factor, and immunocompromised patients = 18 years old, all regardless of COVID-19 vaccination status. The study is expected to have a global footprint with approximately 300 clinical trial sites in the U.S., Europe, Japan and rest of the world.