AstraZeneca is changing the label for its non-small cell lung cancer agent, Iressa (gefitinib), which will see the drug’s use severely limited, after the US Food and Drug Administration agreed with data revealed late last year showing that there was no overall survival benefit amongst patients taking the drug in a major clinical trial [[20/12/04b]].

Patients already taking Iressa in the US – who number approximately 4,000 – can continue to receive the drug through a special access programme run by the Anglo-Swedish company. However, no new patients will be allowed access to the therapy unless they are taking part in a clinical trial. The access scheme will continue “pending availability of new data that would support an additional revision to the label, or possible future withdrawal.”

Iressa won the US green light in May 2003 under the FDA’s accelerated approval programme, which permits approval based on a surrogate endpoint – such as a sign of a disease or the results of a laboratory test – that is considered reasonably likely to predict clinical benefit (improved symptoms or survival) [[06/05/03a]]. Clinical trial data showed that it caused a significant reduction in tumour size in about 10% of patients, and this was thought likely to increase patients’ overall survival time. However, one requirement for drugs approved under this programme is that the firm must study them further after approval to verify the expected clinical benefit, which is where the so-called Isel trial comes in to play. This Phase III study, released in December, showed that Iressa did not produce a statistically significant survival advantage over placebo in patients with advanced NSCLC. The product had been touted as a potential blockbuster earner for AstraZeneca, and brought in sales of $389 million dollars in 2004. However, this figure will likely fall significantly over the coming months on the back of the latest news.

AstraZeneca says it is continuing to evaluate potential predictive biomarkers to better identify more readily those patients who are most likely to benefit from Iressa.