After a two-day hearing, advisors to the US Food and Drug Administration have again voted to recommend withdrawing approval of Roche's blockbuster Avastin as a treatment for breast cancer.
A panel from the agency’s Oncologic Drugs Advisory Committee (ODAC) voted 6-0 that Avastin (bevacizumab) is ineffective for first-line HER2-negative metastatic breast cancer and in another unanimous vote said the drug has not been shown to be safe. The decision was not especially surprising, given that the ODAC voted 12-1 in July 2010 to remove the breast cancer indication for Avastin in combination with paclitaxel, which got the green light in February 2008 under the agency’s accelerated approval programme.
Five of the six members of the panel also voted against Avastin's use in breast cancer after the aforementioned review in July last year and have not been swayed by Roche's arguments concerning safey. The ODAC also rejected a compromise proposed by Roche's Genentech unit that the approval be retained while the company conducts another clinical trial.
Mikkael Sekeres of the Cleveland Clinic Taussig Cancer Institute and one of the panellists, was quoted as saying that "no matter what way we look at it, there's nothing we can hang our hat on in these studies that would make me feel comfortable continuing to expose a lot of patients to risk without a clear benefit".
Natalie Compagni-Portis, the patient representative on the panel, noted that "this is an emotional issue,", adding that "I think we all wanted Avastin to succeed. The reality is these studies we’re hearing about did not confirm that. These studies did not bear out this hope".
FDA Commissioner Margaret Hamburg will make the final decision on whether Avastin should remain approved for metastatic breast cancer, though no specific date has been given. Until then, Genentech noted that Avastin is still available for that indication and this latest vote has no impact on its other approved uses.
Roche hopes to find a solution
Chief medical officer Hal Barron said “we are very disappointed by the committee’s recommendation and hope the Commissioner does not decide to remove this important medicine for women with an incurable disease who already have too few treatment options”. He added that “we remain ready to collaborate with the FDA to find a solution that is in the best interest of patients who need Avastin".
If the ODAC's decision is acted upon, Roche stands to lose a lot of cash. Avastin had sales of 6.46 billion francs in 2010, up 9%, but the company reduced its peak sales estimates for 2011 to 7 billion francs from a previous forecast of 9 billion francs, due mainly to the proposal to pull the breast cancer indication. Without FDA approval, insurance companies and US government health programmes are unlikely to cover the costs of the $50,000-$100,000-a-year drug for an estimated 17,000 women in the USA who use the treatment.
Avastin EU label for breast cancer expanded
Bad news from the USA but in Europe the picture is more positive. Indeed, this morning, the European Commission has extended the existing Avastin metastatic breast cancer label to include combination with Xeloda (capecitabine), in addition to the previous approval for the paclitaxel combo.
The label extension is based on data from the Phase III RIBBON 1 study which showed a significant increase in the length of time women lived without their disease getting worse when Avastin was combined with capecitabine compared to those who received Xeloda alone.