Virus World

Atea Pharmaceuticals said Tuesday that its antiviral pill for Covid-19 failed to combat the virus in a mid-stage trial, leading the company to delay its pivotal study by a year.  The disappointing news follows a far more hopeful October update from Merck, whose similar antiviral reduced the chances that patients newly diagnosed with Covid-19 would be hospitalized by about 50% in a Phase 3 study. There is a desperate need for treatments for early Covid that can be taken as pills. Current treatments, such as remdesivir and monoclonal antibodies, are generally given intravenously or as injections, and are difficult to distribute to large numbers of people. The hope is that pills to treat Covid could be given widely in order to prevent infected people from progressing to severe disease, hospitalization, or death. Atea, partnered with global drug maker Roche, said its drug, AT-527, failed to beat placebo at reducing the amount of measurable virus in patients with mild or moderate Covid-19, missing the primary endpoint of a 100-patient trial. As a result, Atea and Roche are rethinking their Phase 3 trial. That study, designed to enroll up to 1,400 patients, has a primary endpoint of reducing the time it takes patients to recover from Covid-19 and secondary goals including preventing hospitalization. In light of the Phase 2 results, Atea and Roche are now considering whether to change the primary endpoint and target population. Data from that study, once expected this year, are now slated for the second half of 2022, Atea said.

AT-527 works similarly to Merck’s drug, molnupiravir, and was widely expected to succeed in clinical development. The problem might have been trial design. While Merck deliberately excluded patients who had been vaccinated for Covid-19, Atea did not, which might have skewed the results, according to the company. Merck also recruited only patients who had at least one risk factor for severe Covid-19, such as obesity or heart disease, while Atea required only a positive test and mild symptoms.  In a subgroup of patients at high risk for severe Covid-19, AT-527 outperformed placebo at reducing virus levels over seven days, Atea said, which could inform the company’s changes to its Phase 3 trial. “Based on what we know now, this actually is not surprising, as other direct-acting antivirals, including molnupiravir, have shown similar outcomes in the mild-to-moderate outpatient population,” Atea CEO Jean-Pierre Sommadossi said on a conference call with analysts Tuesday. “What is reassuring is that viral reduction … was observed in high-risk patients with underlying health conditions.” The news is a bitter disappointment for Atea, which has spent the past 18 months touting the potential of AT-527, developed as a treatment for hepatitis C, to change the course of the Covid-19 pandemic. The company, which commanded a market value of about $3.4 billion as of Monday, fell 70% in premarket trading on Tuesday. Merck, partnered with Ridgeback Biotherapeutics, is seeking an emergency use authorization for its Covid-19 antiviral and will make its case to a panel of Food and Drug Administration advisers on Nov. 30. Results for another potential oral Covid-19 treatment, from Pfizer, are expected by the end of the year.

Atea Pharmaceuticals Press Release (Oct. 29, 2021): 

https://ir.ateapharma.com/news-releases/news-release-details/atea-pharmaceuticals-provides-update-and-topline-results-phase-2 

Roche is paying Atea Pharmaceuticals $350 million upfront for the ex-U.S. rights to COVID-19 antiviral AT-527. The oral direct-acting antiviral is set to enter a phase 3 trial in non-hospitalized patients early next year, giving Roche and Atea a shot at establishing it as the go-to early treatment for COVID-19. Atea put its COVID-19 program on the map in May when it raised $215 million in a round led by Bain Capital Life Sciences. Up to that point, Atea was perhaps best known for being set up by Jean-Pierre Sommadossi, co-founder of Sovaldi developer Pharmasset. 

Reflecting Sommadossi’s background, Atea initially studied its oral purine nucleotide prodrug AT-527 in hepatitis C, before the pandemic and in vitro evidence of efficacy in coronaviruses persuaded it to target SARS-CoV-2. A phase 2 trial of 190 hospitalized patients with moderate COVID-19 got started in May and is due to wrap up around the end of the year, according to ClinicalTrials.gov.  “AT-527 is expected to be ideally suited to combat COVID-19 as it inhibits viral replication by interfering with viral RNA polymerase, a key component in the replication machinery of RNA viruses,” Sommadossi said in a statement. The phase 2 results will provide a clearer picture of whether AT-527 is efficacious in COVID-19, but Roche has already seen enough to bet $350 million and commit to milestones and royalties. The outlay secures Roche ex-U.S. rights to AT-527. Atea will retain responsibility for distributing the drug in the U.S., although it has an option to ask for the support of Roche’s Genentech. 

While AT-527 is currently in development in hospitalized patients, Roche centered its discussion of the value of the drug on its potential role in non-hospitalized patients. As an oral small molecule, AT-527 has several potential advantages over anti-SARS-CoV-2 antibodies outside of hospital settings. AT-527 stands to be cheaper, easier to administer and manufactured at larger quantities.  Atea and Roche plan to start a phase 3 trial in non-hospitalized patients in the first quarter of 2021. By then, the U.S. and other countries may have begun vaccinating their populations against the novel coronavirus, thereby beginning the process of bringing the pandemic under control. However, with the rollout of immunization programs taking time and vaccines likely to only offer partial protection, Atea and Roche are betting there will remain a need for treatments for some time.   Roche foresees AT-527 being used to treat patients early, perhaps even in post-exposure prophylactic settings. Widespread access to an effective early treatment could stop some cases from progressing to severe COVID-19, thereby improving patient outcomes and reducing the burden on healthcare systems.  The deal opens up another front in Roche’s response to the pandemic. In August, Roche secured the ex-U.S. rights to Regeneron’s REGN-COV2, securing itself a leading spot in the race to bring COVID-19 antibody therapies to market. The deals position Roche to apply its development and manufacturing muscle to drugs with the potential to defang SARS-CoV-2.