Atea and Roche's COVID-19 antiviral flunks phase 2, prompting switch that will delay pivotal data

Atea Pharmaceuticals and Roche have suffered a big blow to their bid to bring an oral antiviral for COVID-19 to market. A phase 2 trial of the candidate missed its primary endpoint, prompting Atea and Roche to consider changes that will delay data from a pivotal study by around one year. 

Merck and Ridgeback Biotherapeutics recently raised hopes that oral antivirals may be effective in at least some COVID-19 patients by presenting top-line data on molnupiravir. The Atea phase 2, which had important design differences to the molnupiravir study, suggests the path to the availability of several oral antivirals will be bumpy.

Atea’s clinical trial enrolled patients with mild to moderate COVID-19, around two-thirds of whom were low risk with mild symptoms. In the overall study population, Atea’s antiviral, AT-527, was no better than placebo at driving declines in SARS-CoV-2, causing the trial to miss its primary endpoint.

The setback left Atea looking to a subgroup of high-risk patients with underlying health conditions for reasons to be cheerful. In the subgroup, Atea saw reductions in viral load in patients on AT-527, although only the analysis of recipients of the low dose of the antiviral candidate was prespecified. 

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AT-527’s failure to drive down viral load in the overall population has led Atea and Roche to rethink the design of their MORNINGSKY phase 3 study. The partners are yet to finalize the changes, but they could amount to a major rethink, with the primary endpoint and patient population among the subjects that are up for discussion. 

MORNINGSKY is currently enrolling up to 1,400 patients with mild to moderate COVID-19. None of the inclusion criteria dictate that the patient needs to have comorbidities or other attributes that put them at high risk of disease progression. The primary endpoint of the study is time to alleviation or improvement of COVID-19 symptoms.

If, as the phase 2 data suggest, AT-527 has no significant effect on the speed at which many patients clear SARS-CoV-2, it is questionable whether the antiviral candidate can reduce the time to symptom alleviation or improvement in the broad population. Narrowing enrollment to patients at high risk of disease progression may increase the chances of success but shrink the addressable population. 

Whatever Atea and Roche settle on looks set to delay the phase 3 data drop. Atea previously aimed to deliver results in the second half of 2021. Now, the biotech is aiming to have data in the second half of 2022. The setback caused gyrations in multiple stocks, with shares in Atea falling 75% to $10 while Merck enjoyed a 3% bump, moving its price up above $79.