Iressa Drug Harm

1. a breakthrough cancer drug

Iressa ®︎ is an anticancer drug for particularly serious lung cancer, and has a different mechanism of action from previous anticancer drugs as a molecular-targeted drug (acting on specific molecules that cause the disease). Iressa ®︎ was a new drug developed overseas, but in July 2002, it was approved in Japan before any other country in the world through a priority review process while it was still unapproved overseas. This priority review was also a response to the “drug lag” problem, whereby drugs were approved more slowly in Japan than overseas at the time. Iressa ®︎ was widely reported in the mass media and was described as a “dream new drug” that, unlike conventional anticancer drugs, could be administered orally once a day and taken in an outpatient clinic, with few side effects and high therapeutic efficacy. It was a promising new drug for lung cancer patients, and it became a drug that could be used during the period between its approval and its inclusion in the NHI drug price, when it was not covered by health insurance. It was also prescribed to patients who had left the care of their physicians and were recuperating at home.

However, as its use expanded, companies reported a number of serious side effects such as acute lung injury and interstitial pneumonia to the MHLW among patients who had taken Iressa ®︎. In response, in October 2002, the MHLW ordered pharmaceutical companies to issue an urgent safety information on side effects and to revise the package insert. Despite this, lung damage and deaths continued to occur, and in December 2002, the MHLW convened a “Gefitinib Safety Issues Study Group” and ordered further revisions to the package inserts. After the revision of the package inserts, which included explaining side effects to patients and providing consent, and requiring observation regarding administration, the number of side effects and deaths has decreased when the drug is used appropriately. However, as of the end of March 2010, there have been a cumulative total of 1,916 reports of interstitial pneumonia and other lung disorders caused by taking Iressa ®︎, with 734 deaths.

Overseas, the application for approval of Iressa ®︎ was withdrawn in 2005 in the EU after clinical trials showed that there was no statistical difference in the life-prolonging effect of Iressa ®︎ between the groups that received the sham drug.

2. the victims’ families’ raising of the issue and the defendants’ backlash

While Iressa ®︎ was approved with high expectations as a “dream new drug,” it faced a number of problems, including the fact that the seriousness of side effects was often overlooked, medical institutions were not fully informed, and the drug was approved without evaluation of its effectiveness in prolonging life.

In 2004, a group of victims filed lawsuits in the respective district courts of Osaka and Tokyo to hold the government and the pharmaceutical company responsible. The Iressa trial had a different nature from previous drug-attack trials, as some patients were still benefiting from the drug, which was still on the market, while others were wondering what to think about the severe side effects for serious cancer patients.

In 2011, the Osaka and Tokyo settlements were issued, respectively, and the government and companies were found to be responsible for the cases prior to the issuance of the emergency safety information. The plaintiffs accepted the settlement, but the Japanese Medical Association and other groups criticized the settlement, and a movement spreading among experts and cancer patients to defend the defendants’ side. It was revealed that the document submitted by the plaintiffs criticizing the settlement had not been prepared voluntarily by the medical society, but had been drafted by the Ministry of Health, Labor, and Welfare, and the collusion between the government and the academic world was also called into question. The defendants, the national government and pharmaceutical companies, refused to accept the settlement, and both plaintiffs and defendants appealed. The high court overturned the district court decision in its entirety, holding neither the government nor the pharmaceutical companies liable for the fact that the description in the package insert was initially inconspicuous, on the grounds that “if the drug was listed as an important side effect, specialists should have been able to recognize it regardless of the manner in which it was listed. After the High Court decision, the plaintiffs wished to appeal the case, but the Supreme Court dismissed the appeal and the plaintiffs lost the case in its entirety.

3. the problems posed by the Iressa drug hazard in the present age

The loss of the case in court made Iressa drug-related injuries not officially recognized by the government. However, the Iressa drug injury still raises important issues today. First, drugs require continuous follow-up from development to post-marketing. And the limited safety and efficacy findings obtained during the drug development phase indicate the need for continuous monitoring of adverse drug reaction reports after the drug is marketed. In addition, since 2017, this has led to a “conditional approval system” that allows drugs for rare diseases for which there are few treatments to be marketed at a stage before clinical trials are conducted. With new drugs now available at a stage where safety has not necessarily been ensured, it is necessary to consider whether the severity of side effects is underestimated in relation to the severity of symptoms.

References

1. Doi, Osamu, 2019, “Postwar Drug Cases: Overview and Lessons Learned” (retrieved February 11, 2025, from https://www.pmrj.jp/publications/02/shiryo_slides/yakugai_shiryo_sengo.pdf).
2. Hanai, Jugo, 2023, “Iressa Yakuhen – Kokkoku ga yakuhen to shite no yakuhen” [Iressa Yakuhen – The State Does Not Recognize It as Yakuhen], Yakuhen wa nanika – Shinnew Yakuhen no Shakaigaku [What is Yakuhen – A New Sociology of Yakuhen?
3. Iressa Drug Victims Association, 2020, “Iressa” (retrieved February 11, 2025, from http://hkr.o.oo7.jp/yakugai/forum/forum22-data/Iressa.pdf).
4. Foundation for Regulatory Science of Pharmaceuticals and Medical Devices, 2012, “Lessons Learned from Drug Injury: Voices from Victims Hoping for the Prevention of Recurrence,” Yakuji Nippo Co.
5. Japan Association for Public Publications, 2011, “Knowledge of Drug Hazards You Should Know–To Prevent Health Damage Caused by Drugs,” Jiho.