AstraZeneca's chances of getting a quick approval in the USA for Brilinta after regulators said it needs another six months to review the much-touted anti-clotting agent. The firm has also ended development of its prostate cancer drug zibotentan as monotherapy.
In December, the US Food and Drug Administration requested additional analyses of data from the 18,000-patient PLATO study, though many observers believed the agency was going to follow its counterparts in Europe and approve Brilinta (ticagrelor) for acute coronary syndromes. Just a month later, AstraZeneca responded to the complete response letter issued by the FDA, which did request additional trials, saying that supplementary analyses it has submitted support the hypothesis that the difference in treatment effect observed in the US and non-US patient subsets in PLATO "is most likely a reflection of an underlying interaction between ticagrelor and higher doses of aspirin".
The Anglo-Swedish drugmaker was waiting to see whether its resubmission would be designated as Class 1 (ie a two-month review cycle) or Class 2 (six months). The FDA has plumped for the second option and set a new Prescription Drug User Fee Act date of July 20.
AstraZeneca said it "remains confident in the New Drug Application submission for ticagrelor and will continue working with the FDA to progress towards completing the review".
Analyst Navid Malik at Matrix Corporate Capital issued a research note saying if approved in the USA, Brilinta (known as Brilique in Europe) may have its label restricted against high-dose aspirin, "which will limit its commercial opportunity and there may be a requirement for a further clinical study post-approval". He added, however, that he still expects Brilinta to be a $2 billion drug.
Zibotentan fails in Phase III
Arguably worse news for AstraZeneca was the announcement that its Phase III ENTHUSE Study 15, studying zibotentan monotherapy in patients with non-metastatic castrate resistant prostate cancer (CRPC), will be stopped. The decision was taken following the results of an early efficacy review by an independent data monitoring committee which indicated that the drug on its own was unlikely to meet its primary efficacy endpoints (progression free survival and overall survival).
AstraZeneca felt "it was prudent to take an early view on the progress of Study 15 following the announcement in September last year that ENTHUSE Study 14, evaluating zibotentan monotherapy, did not show a significant improvement in the primary endpoint of overall survival in patients with metastatic CRPC". It is now giving up on the zibotentan monotherapy programme but ENTHUSE Study 33, a trial using zibotentan in combination with standard chemotherapy in a more advanced metastatic CRPC setting, will continue. Full results are expected in the second half of 2011.