S-217622 is an investigational 3CL protease inhibitor that was studied for once-daily oral administration in mainly vaccinated patients (~85%), with no risk factors for severe complications, within five days of COVID-19 symptom onset.

At the meeting, Shionogi presented new late-breaking Phase 2b results from the Phase 2/3 clinical trial of S-217622, completed in Asia (presenter: Norio Ohmagari, Disease Control and Prevention Center, National Center for Global Health), which followed previously reported topline results from the Phase 2b study. These new data showed:

Antiviral effect:      

・S-217622 demonstrated rapid clearance of the infectious SARS-CoV-2 virus.

・On day four of treatment (following the third dose), the proportion of patients with positive viral titer decreased by approximately 90% versus placebo.

・S-217622 shortened infectious virus shedding by 1-2 days versus placebo.

・S-217622 showed a significant reduction in viral RNA on days 2, 4, 6 and 9 versus placebo (difference versus placebo in the Least Squares mean change from baseline in viral RNA; under -1.0 logx copies/mL on day four at each dose).

Clinical symptom improvement:

・There was no significant difference in total score of 12 COVID-19 symptoms between treatment arms, however, S-217622 showed improvement in composite score of five “respiratory and feverish” symptoms (post-hoc analysis).
 
Safety:

・Both the Phase 1 and 2a/b parts of the Phase 2/3 clinical trials showed that S-217622 was well-tolerated, with few discontinuations due to drug, and no reports of serious adverse events or death. Treatment-emergent adverse events in these trials were generally mild to moderate, and resolved without treatment.

The Phase 2b study was conducted with 428 patients in Japan and South Korea. Its main purpose was to confirm the antiviral effect and clinical symptom improvement of S-217622 when orally administered once daily for five days, versus placebo.

A second late-breaking presentation by Shionogi reported results from both the Phase 1 clinical trial and the Phase 2a part of the Phase 2/3 clinical trial of S-217622 completed in Japan (presenter: Hiroshi Yotsuyanagi, The Institute of Medical Science, The University of Tokyo), which demonstrated it was generally well-tolerated, and rapidly cleared SARS-CoV-2. 

“These results demonstrate that S-217622 rapidly eliminates SARS-CoV-2 in patients versus placebo, marking its potential, if approved, as an effective treatment option for COVID-19. As infections continue to rise in areas worldwide, it is important we have access to a range of easily administered treatment options to ease the pressures on our healthcare systems,” said Isao Teshirogi, Ph.D., President and CEO at Shionogi & Co., Ltd. “We look forward to continued study of this antiviral in Phase 3 trials.” 

A separate global Phase 3 study of S-217622 is underway aiming to recruit participants globally to support regulatory filings this year.