Japan's Osaka District Court late last week ordered AstraZeneca to pay 60.5 million yen - or about $733,000 - to nine of 11 plaintiffs for failing to include proper warnings about serious side effects on the labeling for its Iressa lung cancer med when it was approved in the country in July 2002. However, the three-judge panel ruled the Japanese government was not liable for any damages.
At issue was interstitial lung disease, or ILD, which was cited in 810 deaths through March 2010, according to Medwatcher Japan, a non-profit watchdog, and attorneys who represent the plaintiffs. They argued AstraZeneca downplayed safety issues by failing to prominently note on the labeling the potential for ILD at the time of approval and then advertised Iressa as "anti-cancer drug with little side effect."
The Japanese government, meanwhile, was accused of responding too slowly to side effect reports - there were 13 deaths and 26 cases of ILD recorded within three months after Iressa was approved, but only in October 2002 did the goverment issue a safety alert. And while a domestic Phase III trial was conducted as a condition for approval, the study failed to prove a survival benefit, but plaintiffs maintain the goverment should have reviewed its decision to approve the med.
Iressa, you may recall, has had a troubled history. In the US, follow-up studies required as a condition of FDA accelerated approval in 2003 failed to show a survival benefit and Iressa was withdrawn, except for patients already being treated. Earlier this month, AstraZeneca finally gave up altogether on seeking FDA approval (see here), although existing patients can continue to receive treatment through a clinical study.
Two different groups of patients or their survivors in Japan subsequently filed separate lawsuits in Osaka and Tokyo courts in 2004, citing the government's failure to limit usage as regulators did in other countries and AstraZeneca promotional material that described Iressa as a dream drug. "This exaggerated marketing strategy and advertisement contributed to a rapid increase of casualties during the short period of time after the approval," Reika Suzuki, one of the attorneys, writes us. "The court clearly said that Astrazeneca failed to include sufficient explanations in the package insert about the side effects of Iressa at the time of its approval."
The atmosphere surrounding the litigation grew more intense, by the way, after the watchdog and attorneys discovered conflicts of interest involving the Iressa guidelines committee, which was established in 2005 by Japan's Ministry of Health, Labor, and Welfare. Nine of 10 members either served as expert witnesses for AstraZeneca in various litigation, worked on Iressa clinical trials or belonged to the West Japan Oncology Group, a non-profit devoted to cancer treatments that received funding from AstraZeneca, according to Japan Medwatcher (read this).
"The Osaka District Court clearly pointed out that AstraZeneca insufficiently warned against fatal ILD in the first version of the package insert until it released the urgent safety information on October 15 2002," Suzuki writes us. "As for the court’s rejection of the government’s responsibility, we are not satisfied. We find that it is very contradictory that the court denied the state’s responsibility while saying that the administrative guidance was not enough...It is very absurd that the government could not issue the administrative guidance to the company’s package insert when the fatal risk was clear."
While maintaining the ruling is of "historical importance" because it serves as a reminder for drugmakers to provide proper warnings, Suzuki also says the lack of government responsibility is unjust. "The people’s trust toward adequate drug-policy administration cannot be maintained if state liability is denied when it allows marketing of such defective drugs. The state has to take responsibility for properly instructing and directing drugmakers to maintain drug safety."
Meanwhile, another group of lawsuits will be heard later this month in Tokyo district court, so the potential for a different outcome remains on the table. As for AstraZeneca, a spokeswoman sent us a statement saying the drugmaker "AstraZeneca will evaluate the details of the ruling to determine next steps and whether it may appeal to the Osaka High Court. We have consistently and appropriately been informing physicians about the risk/benefit profile of Iressa and the role it plays in the treatment of this deadly disease since its launch."