Health ministry questions reliability of vasculitis drug approval data

Japan’s health ministry said Wednesday that there may be problems with the reliability of documents submitted by Kissei Pharmaceutical for the approval of vasculitis drug Tavneos.

In its response to a series of deaths among Tavneos users, the ministry reiterated its request that medical institutions refrain from starting new patients on the drug, which is marketed by Kissei Pharmaceutical, based in Matsumoto, Nagano Prefecture.

The ministry plans to decide by the end of this year on administrative action, potentially including revocation of the drug’s approval.

Tavneos was launched in Japan in June 2022 after receiving approval from the ministry. Its package insert listed liver dysfunction as a serious side effect.

Kissei Pharmaceutical reported in May this year that 20 Tavneos users had died of liver dysfunction. It was later found, however, that one of the reported deaths was due to another factor.

According to the ministry, four additional fatal cases have since been confirmed, taking the total number of deaths from liver dysfunction to 23. In six of the cases, a causal relationship with the drug could not be ruled out.

The ministry approved Tavneos based on the results of a clinical trial conducted by the U.S. pharmaceutical company that developed the drug. Regulatory authorities in the United States and Europe have raised concerns about the appropriateness of the trial methodology, however.

European authorities revoked the drug’s approval in August, while U.S. authorities recommended that the approval be withdrawn.

In June, the ministry ordered Kissei Pharmaceutical to submit a report on the drug. The Pharmaceuticals and Medical Devices Agency analyzed the company’s response and compiled a report.

In the report, the agency said that the clinical trial results may have reliability issues and that it was inappropriate to use them as evidence of the drug’s efficacy. Regarding safety, it said that measures taken since May have had some effect, while noting that liver dysfunction still requires close attention.

The agency also said that it could not conclude that the drug’s benefits outweigh its risks.

Following the report, the ministry called on medical institutions to refrain from starting new patients on the drug. However, given that it is used to treat serious designated intractable diseases, the ministry asked medical institutions to make discontinuation of the drug or a switch to alternative therapies the general rule for patients already receiving it.