A day after giving an expected thumbs down to Amgen’s bone cancer drug Xgeva in a prevention setting, an FDA oncology advisory panel made it two out of two when it voted 10-3 against extending use of Astex Pharmaceuticals' and Eisai’s Dacogen in the additional indication of acute myelogenous leukaemia (AML).
As in the case of Xgeva, not only was the outcome widely predicted, the panel again erred on the side of caution and decided that the risk of the drug for patients aged over 65 and not eligible for chemotherapy outweighed any benefits. The US regulator will now decide the fate of Dacogen in AML on March 6, but with such a decisive vote against approval it is unlikely a green light will be given.
However, as previously argued by EP Vantage US approval was never a key event for Dacogen, which is already marketed in myelodysplastic syndrome and faces a patent expiry in the region by 2013 (Event - AML would be a useful extension to Dacogen label, January 19, 2012). Instead it was an important marker in the sand as to the drug’s potential fate in the Europe, where it has never been sold, and if approved would have given ex-US partner Johnson & Johnson 10 years of market exclusivity and 10 more years of royalties for originator Astex.
Astex shares, which had already been hammered earlier in the week when the FDA released the briefing documents for the panel, questioning the risk benefit of the drug, fell a further 8% yesterday to $2.01.
The European decision is expected in the second half, but the negative opinion from the US advisory committee will now almost certainly cast doubts on it being treated any more favourably across the pond.
Certainly Dacogen’s record in clinical trials has not helped. In phase III trials the drug failed to show any statistical benefit over low doses of chemotherapy. But the fact that the FDA bothered to convene an advisory committee rather than just reject the drug out of hand demonstrates the desperate desire to find a treatment for this disorder. And during the panel discussions more than one of the panellists expressed their desire to find a suitable treatment for AML.
This is a challenge that has defeated several companies. Most recently Seattle Genetics halted development on its phase IIb antibody lintuzumab (SGN-33) in September after the drug failed in trials. Earlier in 2011, Pfizer voluntarily withdrew its marketed drug Mylotarg following concerns over efficacy and safety. Mylotarg had been brought to market in 2000 under an accelerated approval programme, but failed to show efficacy in subsequent confirmatory trials.
But it is this difficulty in developing drugs in what is a very sick patient population that might save Dacogen from rejection outside of the US, despite the negative looking omens. The drug has orphan status in Europe and the regulators there might be more inclined to consider the trend towards efficacy the drug has shown in follow-up studies.
If they do, and right now few bets might be taken on a positive outcome, not only will patients have a much needed therapy, but Astex could see a little bit more growth out of its most valuable product.