AT 527, an oral antiviral reduces viral replication in hospitalized patients with COVID-19 in phase II interim analysis. Atea + Roche

The interim analysis of the Phase II study included data from 70 hospitalized, high-risk patients with COVID-19 of which data from 62 patients were evaluable for virology analysis. Interim virology results indicated that AT 527 rapidly reduced viral load levels . At Day 2, patients receiving AT 527 experienced a 0.7 log10 (80%) greater mean reduction from baseline viral load as compared to placebo. A sustained difference in viral load reduction was maintained through Day 8.

AT 527’s SARS-CoV-2 potent antiviral activity was also observed in patients with higher baseline viral loads above the median of 5.26 log10 as compared to placebo. When evaluating a strict RT-qPCR threshold of 500 copies/mL with no detectable ribonucleic acid (RNA) virus (target not detected, TND), the AT 527 arm achieved SARS-CoV-2 clearance as early as Day 2 (in 6% of patients), Day 8 (in 7% of patients) Day 10 (in 33% of patients), and Day 12 (in 31% of patients) compared to 0% of patients in the placebo arm at the same timepoints. By Day 14 (last viral sampling study day) approximately 47% of patients in the AT-527 arm and 22% in the placebo arm had no detectable RNA virus (TND). Nasopharyngeal swabs were measured in a reverse transcription polymerase chain reaction test (RT-qPCR) for the quantitative detection of nucleic acid from SARS-CoV-2.

Consistent with previous studies, AT 527 was generally safe and well tolerated. In this hospitalized study, there were no drug-related serious adverse events. Non-serious adverse events were equally distributed across treatment arms. Most were mild-to-moderate in severity and assessed as not related to the study drug. No safety concerns or newly determined risks were identified. Final data from the full Phase II program will be submitted to an upcoming medical congress or a peer-reviewed publication.

About the Global Phase II Study of AT 527 in the Hospitalized Setting :The global Phase II trial in the hospital setting is a randomized, double-blind, placebo-controlled, multi-center study to evaluate AT 527 in patients with moderate COVID-19. Study objectives are to assess safety, tolerability, clinical and antiviral efficacy. Patients were randomized less than 5 days of symptom onset to receive either AT 527 550 mg twice-daily (BID) or placebo BID dosed for 5 days. The key inclusion criteria for this study were adult patients greater than 18 years old with risk factors such as obesity, diabetes and hypertension. Results from this Phase II study in hospitalized patients included pre-specified, interim virology data. This Phase II study was designed to gain confidence around the safety and tolerability of AT 527 and was not powered to show definitive clinical outcomes, which are being evaluated in the global Phase III MORNINGSKY trial.

The evaluation of infectious virus (viable virus able to replicate in cell culture) was an exploratory endpoint in this study and the current standard assay used was not able to measure the infectious virus in > 95% of the nasopharyngeal samples.