Atea Pharmaceuticals provides update and topline results for phase II MOONSONG trial.

However, in high-risk patients with underlying health conditions, a reduction of viral load of approximately 0.5 log10 at Day 7 was observed at 550 mg (prespecified subgroup analysis) and 1,100 mg BID (exploratory subgroup analysis) compared with placebo.

Based on the MOONSONG topline and additional recent results for AT 527 as well as the evolving COVID-19 environment, Atea, together with Roche, are assessing potential modifications to the global Phase III MORNINGSKY trial including the trial’s primary endpoint and patient population. As a result, we now anticipate Phase III MORNINGSKY data in the second half of 2022.

Atea and Roche are jointly developing AT 527 as an oral direct-acting antiviral (DAA) for the treatment of COVID-19. Its unique mechanism of action, with dual targets including chain termination (RdRp) and NiRAN inhibition, has the potential to create a high barrier to resistance with broad antiviral coverage to different variants of SARS-CoV-2. Atea has completed a comprehensive nonclinical program to characterize the safety profile of AT 527. Results from these nonclinical studies demonstrate that AT 527 is non-mutagenic and has no effects on fertility and reproduction.

Topline Results of Global Phase II MOONSONG Trial of AT 527 in the Outpatient Setting ; The global Phase II MOONSONG trial is a randomized, double-blind, multi-center, placebo-controlled trial, evaluating the antiviral activity, safety and pharmacokinetics of AT 527 550 mg (Cohort A, n=30) and 1,100 mg (Cohort B, n=30) administered twice daily (BID) in adult patients with mild or moderate COVID-19 versus placebo (n=40). The primary endpoint of this virology trial, which enrolled patients who were SARS-CoV-2 positive, is change from baseline in amount of SARS-CoV-2 virus RNA as measured by RT-PCR at specified timepoints.

In the topline analysis, treatment with AT 527 did not meet the primary endpoint as it did not show a clear reduction in SARS-CoV-2 viral load in the overall population of patients with mild or moderate COVID-19 compared to placebo. Overall, approximately two-thirds of the patients had mild symptoms with no underlying health conditions and were on average 37 years old. Additionally, COVID-19 vaccinated patients were among the patients included in the overall study population.

In high-risk patients with underlying health conditions, a reduction of viral load of approximately 0.5 log10 at Day 7 was observed with administration of 550 mg as compared to placebo (prespecified subgroup analysis Cohort A n=7; placebo n=11) and with administration of 1,100 mg BID as compared to placebo (exploratory subgroup analysis Cohort B; n=14; placebo n=7). In addition to baseline patient characteristics, several factors may have impacted the MOONSONG data results, which evaluated viral kinetics. These potential factors include different variants emerging during the study, greater penetration of vaccinations within the enrolled population and a pooled placebo patient population. The pooled placebo patient population included different vaccination status (varying doses and vaccine types) and may have included different COVID-19 variants.

Consistent with previous studies, AT 527 was generally safe and well tolerated. In the MOONSONG study, the proportion of patients experiencing any adverse event (AE) was 20% in the placebo group, 20% in the AT 527 550 mg BID group (Cohort A) and 27% in the AT 527 1100 mg BID group (Cohort B). There were 3 non-drug related serious adverse events (SAEs) in each of the treatment groups and all other AEs were grade 1 or 2. Gastrointestinal (GI)-related AEs were the most commonly reported AEs: 8% in the placebo group; 7% in the AT 527 550 mg BID group (Cohort A); 17% in the AT 527 1100 mg BID group (Cohort B), with mild to moderate nausea/vomiting resulting in premature study drug discontinuation of 3% in the placebo group, 0% in the AT 527 550 mg BID group (Cohort A) and 17% in the AT 527 1100 mg BID group (Cohort B). No clinically significant differences in laboratory abnormalities were observed in the treatment arms as compared to placebo.

“Based on the totality of the results for AT 527 to-date, the current level of understanding of the virus and the evolving COVID-19 environment, we are assessing the Phase III MORNINGSKY trial for modifications to ensure the best possible outcome for the program,” said Janet Hammond, MD, PhD, Chief Development Officer of Atea Pharmaceuticals. “We, along with our partner Roche, are continuing to advance multiple studies in parallel to provide further clinical evidence as well as outcome data to support AT 527 as an oral, potent, direct-acting antiviral treatment for COVID-19.”

In addition to the MOONSONG results , results from the bronchoalveolar lavage study and Phase II hospitalized trial are being presented at the International Society for Influenza and Other Respiratory Virus Diseases (ISIRV)-World Health Organization Virtual Conference (WHO), in a poster and oral session held virtually October 19-21, 2021.