Why The FDA Rejected A Drug That Helps Cure Lung Cancer -- And What We Can Do To Fix It

     Ed Silverman, writing in the Boston Globe October 19, pointed to lung cancer drug Iressa as a “cautionary tale” against using “surrogate endpoints” – signs that point to, but don’t guarantee, a given clinical outcome – for FDA drug approvals. He suggests that the 21st Century Cures Act, which encourages the FDA to expand use of such tools during drug approvals, is wrongheaded — a view echoed by prominent voices in The New York Times and the New England Journal of Medicine. But the example he used – centered on lung-cancer drug Iressa – proves just the opposite, giving us a textbook case of why surrogate endpoints are a critical tool for advancing new therapies to patients that demonstrate early promise.
Left unmentioned by Silverman was the fact that Iressa recently returned to market in the U.S., with a full FDA approval granted last July – and that Iressa had been marketed for years outside the U.S., in 90 other countries as of 2014. How the FDA rejected and later accepted Iressa vividly illustrates the need for the 21st Century Cures legislation.

In Silverman’s telling of Iressa’s history, the FDA gave patients false hope, approving an expensive, ineffective drug, which manufacturer AstraZeneca (AZ) would later have to pull from the market. But the Iressa story, when fully told, actually demonstrates how surrogate measures can streamline the drug approval process and accelerate the delivery of life-saving treatments.
Iressa was effectively withdrawn in the U.S. in 2005, but it remained on the market in Europe and Asia, where most of the critical research showing its effectiveness took place. In the United States, Iressa had initially received accelerated approval based on its ability to significantly shrink tumors – a surrogate endpoint – in a number of patients. In the confirmatory follow-up trial AZ completed in 2004 (conducted in accordance with standard FDA trial protocols required as a condition of receiving accelerated approval), Iressa-treated patients on average, however, did not fare any better than those who received the standard of care. The FDA responded by limiting access to Iressa to the patients it was already benefiting.
Was the original surrogate endpoint study a fluke and the accelerated approval a mistake? Or was something else happening? In 2004, we just didn’t know why some patients responded so well to Iressa, while others did not.