After Atea Pharmaceuticals reported early data in June showing its Roche-partnered antiviral can slash the SARS-CoV-2 viral load in hospitalized patients, the company unveiled some changes to that phase 2 program to keep up with the “evolving COVID-19 environment.”
Those amendments include changing the phase 2 trial’s primary endpoint from disease progression to virology—namely, the drug’s effect on patients’ viral load—adding 110 more patients in a new cohort and testing higher doses of the treatment. The data reported in June came from 62 of 70 hospitalized patients with moderate COVID-19 symptoms who received the drug, AT-527, or placebo twice a day for five days.
On the second day of treatment in that trial, patients taking the drug had an 80% greater mean reduction from baseline viral load compared to placebo. After two weeks, 47% of the patients who got AT-527 and 22% of those who received placebo had no detectable levels of the virus.
The new trial changes are a product of the speed at which companies have been developing COVID-19 vaccines and therapeutics.
“We are very pleased with the results … But we did not have an opportunity to do a dose response,” Atea CEO Jean-Pierre Sommadossi, Ph.D., told Fierce Biotech.
That’s because the company, like its peers, was working as fast as it could and ran its phase 2 and phase 3 trials concurrently. Now that it’s generated some data, the company can backtrack and look into alternative dosing regimens.
So far, studies of AT-527 have turned up no serious side effects, and no patients have quit the study because of side effects, “so this is a unique opportunity to evaluate higher doses and see if they may have better impact in patients,” Sommadossi said.
The change in primary endpoint stems from the evolution of care for COVID-19 patients. In the fall, about 40% of patients with risk factors such as diabetes or high blood pressure were at risk of their disease worsening to the point of needing mechanical ventilation, Sommadossi said. But as new drugs were developed and standards of care have evolved, this figure decreased, and leaning on rates of disease progression as the trial’s primary endpoint would not be meaningful, he added.
While it plugs away at the phase 2 study in hospitalized patients, the company is also running a phase 2 trial, dubbed MOONSONG, and a phase 3 study, known as MORNINGSKY, in the outpatient setting. It expects to report data for both by the end of the year.
Atea also revealed a follow-on study that will enroll about 1,000 patients from the MORNINGSKY trial to assess the impact of AT-527 in patients who develop so-called “long COVID.” The company hopes the drug can make a dent in patients whose symptoms persist for weeks or even months longer than the virus’s typical life span—particularly in younger people who had milder cases of the disease.
“What we hope to demonstrate is that it is critical, regardless of whether individuals have risk factors or are asymptomatic ... that if we treat them early with a direct-acting antiviral, we have also a positive impact on long-term COVID,” Sommadossi said. It could be particularly important as the more contagious delta variant continues to spread.
Finally, Atea reported data from healthy volunteers showing the drug reached target levels in the fluid lining of the lungs, where the SARS-CoV-2 virus replicates.
“These data not only provide further confidence for treatment but also support development of AT-527 for prophylaxis of COVID-19 … Impacting key sites of infection will be important in helping patients recover faster while minimizing virus transmission,” Sommadossi said in a statement.