Shionogi's COVID-19 antiviral heads to phase 3 backed by NIH after receiving FDA go-ahead

Shionogi's COVID-19 treatment, backed by the National Institutes of Health (NIH), is moving on to phase 3 after the FDA finalized the study design, a positive step after several clinical pauses and discontinuations have marred pandemic research funded by the NIH in March. 

The trial is part of the NIH's ACTIV-2 study, which has been testing a slew of potential COVID-19 outpatient therapies since late 2020. Shionogi executives said in February that the company and FDA were working to finalize the study design to advance S-217622, a once-daily oral antiviral, into late-stage trials. Now that it's a go, the company will recruit roughly 1,700 people across the globe to test the therapy in high-risk, non-hospitalized adults. The trial will be conducted by the AIDS Clinical Trials Group. 

Data from the phase 3 trial could provide a much-needed tiebreaker on the efficacy of the treatment, which so far has had a mixed bag of results. Interim phase 2a results found that S-217622 significantly reduced viral load, but phase 2b data found no major change in clinical symptoms, a failure on the primary endpoint. Using the same mechanism as Pfizer’s Paxlovid, Shionogi’s treatment inhibits the 3CL enzyme, limiting the virus’s ability to replicate. 

In February, Takeki Uehara, vice president of Shionogi’s clinical research department, said they would be adjusting the primary endpoints of the phase 2 trial to prioritize antiviral efficacy over clinical outcomes. Irrespective of the quality of the interim data, Shionogi applied for regulatory approval in Japan saying updated phase 2 data would be supplied to the regulators as it was received.

Analysts at Jefferies said the advancement to phase 3 with the U.S. government was a surprise, as the firm had expected Shionogi to sign a global development deal with a commercial partner instead for S-217622. This would have provided the Japanese company with upfront income and helped validate the therapy, but could cut profits in the long term. Jefferies pointed to the $350 million upfront that Atea Pharmaceuticals received from Roche to develop AT-527 for COVID-19—an ultimately doomed partnership

But the NIH trial for S-217622 is a positive and may ultimately result in better economics overall, according to Jefferies. 

The news stops a pattern of pauses and discontinuations associated with the ACTIV-2 trial, meant to test outpatient COVID-19 treatments, this month. The first came when SAB Biotherapeutics' antibody treatment was axed due to too few omicron-related hospitalizations and deaths. Then Synairgen’s study arm was paused as the study design was reworked for the same reason. Neither Synairgen nor NIH have clarified how the study is being tweaked. 

It’s also unknown whether the depletion of federal funds for pandemic readiness will hinder the NIH’s ability to foot the bill for its trials, including ACTIV-2. Tuesday, the Biden administration outlined how that dwindling pool of cash is likely to impact testing efforts and the supply of COVID-19 treatments.