On April 5, 2012, the FDA Reproductive Health Drug Advisory Committee will discuss the mirabegron application from Astellas for the treatment of overactive bladder. Astellas already has a drug on the market for this indication, VESIcare.
The FDA Briefing Document notes that the drug achieved statistical significance in all 3 of the Phase 3 trials submitted and the secondary efficacy endpoints were consistent with efficacy.
Regarding the safety of mirabegron, the FDA has raised several concerns. There is an increase in both heart rate and blood pressure noted in both Phase 1 and Phase 3 trials that seems to be greater with higher doses. The FDA further states that the size of the data base (presumably too small) prevents them from further evaluation of this observation so the question remains open. They also note an increase in neoplasms but this is probably not an issue as they seem to occur at high doses and seem to consist of neoplasm common to adults. Hepatotoxicity, hypersensitivity and urinary tract infections are also noted but are infrequent and probably not an issue either.
This leaves only the cardiovascular safety issues that should be a concern when considering the benefit risk for this product. How will the Advisory Committee respond to the FDA question regarding benefit risk for this product?
We think there will be a positive vote but it will be close. Why? While the efficacy is positive using the statistical significance measure, the clinical significance of the improvement seems marginal. In fact, if one compares the numbers reported by Astellas in the VESIcare package insert, it appears that mirabegron has slightly inferior efficacy. There are patients who should not take VESIcare that seem to be indicated for mirabegron, so the Urologists on the Advisory Committee may see this as a necessary drug for those patients. The big issue will really be how seriously the FDA takes the cardiovascular risks and how the Advisory Committee responds to those concerns.
It will be close, but we think the Advisory Committee will recommend approval.