JOURNAL OF PHARMACEUTICAL BUSINESS on THE WEB．Let's discuss the money for medicinesCancer drugs recommended in Japan despite being ineffective in the United States. No. 133

Akihiko Ozaki, M.D., Ph.D. Physician at the Medical Governance Research Institute

"We are taking this drug off the market because we cannot prove its effectiveness." Cancer treatment drugs that were deemed this way in the United States are still used as "recommended treatments" in Japan. At least seven cases have been confirmed as of July 2023. This surprising fact was revealed by the authors' latest research, accepted for publication in “Investigational New Drugs” and is due to differences in the drug regulatory systems between Japan and the United States. 

Why is there such an international "twist" regarding a treatment drug that can potentially affect patient's lives? This time, we report the results of a survey on the use of cancer treatment drugs in Japan that have had their approval revoked in the U.S.

This is the U.S. Food and Drug Administration's (FDA) "accelerated approval" system. This is a system designed to quickly get new drugs to patients for serious diseases, with approval being granted based on "surrogate endpoints" such as the rate of tumor shrinkage. Instead, the condition will be that subsequent "post-marketing surveillance" will confirm the drug's true clinical effectiveness, such as extending survival.

In our paper, we investigated how cancer treatment drugs that have been withdrawn in the U.S. are handled in the clinical guidelines of various Japanese specialist societies (Japanese Society of Hematology, Japanese Lung Cancer Society, and Japanese Breast Cancer Society).

As a result, four out of the seven drugs (57%) were "strongly recommended" or "moderately recommended" in the Japanese guidelines. Gemtuzumab Ozogamicin (acute myeloid leukemia), Gefitinib (EGFR gene mutation-positive non-small cell lung cancer), Bevacizumab (HER2-negative metastatic breast cancer), and Atezolizumab (PD│L1-positive triple-negative breast cancer). In any cases, approval was revoked in the U.S. because post-marketing surveillance did not demonstrate any clinical benefits, such as extending overall survival.

In the U.S., there is a system in place to revoke approval if effectiveness is not confirmed in post-marketing surveillance, but in Japan, there is basically no system in place to withdraw a drug from the market after the fact. For example, Gemtuzumab Ozogamicin, which was withdrawn from the U.S. due to concerns about its efficacy and safety, remains approved in Japan for the same indications and at a higher dose. In addition, the clinical effectiveness of drugs such as bevacizumab and atezolizumab is controversial, and their evaluations are divided between Japan and the U.S.

This situation means that there will be disparities in the treatment that patients can receive depending on the region. If the U.S. decision is correct, Japanese patients will receive an unproven drug. On the other hand, if Japan's decision is correct, U.S. patients will lose access to a beneficial drug.

By the way, as a clinical specialist in breast cancer, I regularly use Bevacizumab and Atezolizumab and have seen cases in which they were effective. In particular, in the case where Atezolizumab was used, the patient's condition was serious when treatment began, but by combining surgery and other treatments, the patient is currently in good health. To be honest, without Atezolizumab, the patient would probably have died.

In other words, even if a drug's approval has been revoked in the U.S., it cannot be said with certainty that it is ineffective. What is important is for Japanese regulatory authorities and specialist societies to establish a system of post-marketing surveillance and increase transparency by more clearly explaining the reasons for recommending such drugs.

Additionally, the responsibility of pharmaceutical companies is also important in this issue. Companies have a responsibility to evaluate the efficacy and safety of products even after market approval, and to disclose information transparently. In particular, for drugs that are receiving mixed reviews, companies should build evidence by conducting additional tests themselves.

Ultimately, cooperation between regulators, medical experts and pharmaceutical companies is essential, and international harmonization is required with patient interests as the top priority. Companies must priorities patient safety and health over short-term profits.

This article was originally published in Japanese in Iyakukeizai (Pharmaceuticals and Economics) on March 15, 2025.