COVID pill, ensitrelvir, is for Pharmaceutical Affairs and Food Sanitation Council (PAFSC) review for first emergency approval.

The panel’s approval, if given, is expected to open the way for the drug to become the first product to be approved under this pathway introduced last month.

Shionogi filed the drug, also known as S-217622, in February 2022, seeking the application of the conditional early approval system, which had previously been applied only to cancer and rare disease indications. Japan later amended the Pharmaceuticals and Medical Devices (PMD) Law to create the emergency approval pathway to approve not only products available overseas but also those developed and filed first in Japan to deal with pandemics and other contingencies. According to the Ministry of Health, Labor and Welfare (MHLW), Shionogi requested the conversion of its original application to one seeking emergency approval late May after the enforcement of the amended law. Under the law, the new system will be invoked only when there are no alternative therapies or methods to address emergencies. More specifically, it will be applied when 1) there is no approved drug available, 2) approved drugs alone are not sufficient as a treatment method, 3) approved drugs are not sufficient in terms of stable supplies, and 4) proposed drugs are expected to have prominently higher efficacy or safety as compared to approved drugs.

Emergency approval will be granted based on the risk-benefit balance of each product. Regulatory authorities will assess whether there is “presumed efficacy” demonstrated in clinical trials, while the “confirmation of safety” will be required at the same level as it is now.

Whether S 217622 meets these criteria will be reviewed at the upcoming meeting of the Pharmaceutical Affairs and Food Sanitation Council’s (PAFSC) Second Committee on Drugs. While the Second Committee usually acts as a de-facto decision-making organ for marketing approval, PAFSC rules revised this month stipulate that products proposed for the emergency approval pathway are subject to discussions not only at the First/Second Committee but also at the upper-organ PAFSC. The next PAFSC meeting is set for 24 June but a MHLW official said it is unlikely that ensitrelvir will be taken up there because it “will probably take several weeks from the Second Committee meeting (to reach PAFSC discussions).” No specific timeline has been determined, but the ministry plans to hold a joint meeting of the PAFSC and the Second Committee to discuss the drug publicly.

According to data released by Shionogi in April, ensitrelvir could not show a statistically significant difference versus placebo in the total score of 12 COVID-19 symptoms in a PII/III study. However, it demonstrated an improvement in the composite score of five respiratory and feverish symptoms based on post-hoc analyses. In terms of antiviral effects, the ratio of patients with positive viral titers on Day 4 (following the third dose) declined by some 90% versus placebo.