Iressa fails to prolong life

AstraZeneca has admitted that initial analysis of the primary endpoint of its Iressa Survival Evaluation in Lung cancer (ISEL) trial showed that the drug failed to significantly prolong survival in comparison to placebo in the overall population or in patients with adenocarcinoma.

AZ already faces a delay to Exanta, its blood thinning drug, which US regulators refused to approve earlier this year, while sales of Crestor are being hurt by criticism from FDA medical reviewer David Graham, who told a Senate panel earlier this year that Crestor and four other drugs needed further safety review.

While there was a statistically significant improvement in tumour shrinkage with Iressa (objective response rate), this did not translate into a statistically significant survival benefit.

AZ conducted the new study at the request of US regulators after previous tests failed to show Iressa lengthened patients' lives. CEO Tom McKillop said he didn't know if Iressa would be withdrawn from the market, but said promotion of the drug will stop until the company ends talks with the regulatory agencies.

It is thought the company will be advising oncologists that patients in countries where the drug is approved for lung cancer, for instance the US, should consider taking Tarceva instead because of its improved survival data.

The ISEL study was a very large study that was done in patients who had failed one or more lines of chemotherapy for lung cancer. It was designed to find out whether Iressa would prolong their lives. Patients received either Iressa or a placebo and were followed until they died. The results showed that in the overall population, in all the patients studied Iressa didn't prolong patients' lives. Dr Alan Barge, worldwide medical director for Iressa said: 'When we looked at subsets of patients in the study, we did find that there was a survival advantage in patients from oriental countries and patients who had never smoked. The overall result is clearly very disappointing, for doctors and for patients that they're treating. And it means it shows that Iressa does not confer a survival benefit in the overall population.'

'Iressa clearly provides substantial benefits for some patients in clinical practice and we will be working to better understand this outcome including evaluation of EGFR expression and other biomarkers.'

Full results from ISEL will be presented in the first half of 2005.

'These recent disappointments set in a more hostile environment towards pharmaceutical stocks, have resulted in a substantial loss of value,' McKillop said `I am determined to improve our development and regulatory performance, restore confidence in the company and value to shareholders.'