The FDA’s Pulmonary-Allergy Drugs Advisory Committee (PADAC) will meet on Thursday, February 23 to decide whether or not to approve Forest Labs’ aclidinium bromide inhalation powder for the treatment of COPD. Forest submitted an NDA for the product in June 2011.
In its briefing package for the advisory committee members, the FDA cites known cardiac safety issues for other inhaled anticholinergics, including tiotropium bromide, and questions whether Forest has presented enough data to make a risk-benefit assessment: “Adverse events were generally low in incidence, but the overall long-term safety database for aclidinium 400 mcg BID is relatively modest compared to other COPD development programs. In this context, a small imbalance in cardiovascular deaths was observed for aclidinium 400 mcg, and subsequent additional data from long-term exposure suggests a possible dose-dependence. Whether these results represent a spurious finding or a potential safety signal is difficult to discern and may warrant further investigation. This issue is of particular importance given the concern for possible increased mortality that has been raised with other inhalational anticholinergic agents.”
Briefing materials from Forest suggest that their aclidinium inhalation powder is particularly safe: “Aclidinium bromide is a novel, long-acting dry powder inhaled muscarinic receptor antagonist that is highly selective for the M3 receptor. The M3 receptor mediates bronchodilation in patients with COPD, and the long residence time on the receptor allows for twice-daily (BID) dosing. In addition, aclidinium bromide has very low systemic exposure, which may explain the low incidence of anticholinergic side effects observed in the clinical program. Proper inhalation technique is facilitated by an elegant multi-dose delivery device designed for ease of use and to enhance adherence with prescribers’ instructions. The potential for patient confusion that can occur with device operation with other inhalation devices is minimized with the device (Pressair).”
Questions proposed for the PADAC meeting include:
1. Do the efficacy data provide substantial evidence of a clinically meaningful
benefit for aclidinium 400 mcg twice daily in the maintenance treatment of
bronchospasm associated with COPD? (Voting question)
–If not, what further data should be obtained?
2. Discuss the overall safety profile of aclidinium considering the following
–The size of the safety database
–The duration of exposure
3. Has the safety of aclidinium been adequately assessed for the proposed
indication? (Voting question)
–If not, what further data should be obtained?
4. Do the efficacy and safety data provide substantial evidence to support approval
of aclidinium 400 mcg twice daily for the maintenance treatment of
bronchospasm associated with COPD? (Voting Question)
–If not, what further data should be obtained?
View the FDA briefing materials.
View the Forest briefing materials.
View other PADAC meeting materials.
