Regulatory Decision Summary for Duaklir Genuair

Clinical studies submitted demonstrate that treatment with Duaklir Genuair is effective in reducing both trough forced expiratory volume in 1 second (FEV1) and 1-hour post-dose FEV1 in patients with moderate to severe COPD.

Adverse events commonly associated with Duakli Genuair treatment are generally moderate in severity and are typical of products in this class [that is (i.e.) LABAs and LAMAs and their combinations]. Safety data suggest, the fixed-dose combination treatment does not represent a greater degree of harm, or result in unexpected adverse outcomes as compared to monotherapy products containing either aclidinium bromide or formoterol fumarate, or as compared to other available LABA/LAMA combination products.

One uncertainty associated with Duaklir Genuair is that one of the active ingredients (aclidinium bromide) has been on the market for less than 2 years; therefore post-market experience with this ingredient is limited However, the limited post-market information that is available has not identified any areas of concern.

While specific assessments of subpopulations with hepatic, renal impairments have not been conducted with Duaklir Genuair, the available pharmacokinetic evidence for Duaklir Genuair and the existing labelling (Canadian and/or international) for monotherapy products with aclidinium bromide and formoterol fumarate do not suggest the requirement of any specific warnings or precautionary statements for these subpopulations. Therefore no specific dosage adjustments are needed for these patients.

In clinical studies, patients were excluded from enrollment if they had a myocardial infarction during the previous 6 months, unstable angina, newly diagnosed arrhythmia within the previous 3 months, or hospitalization within the previous 12 months for heart failure functional classes III and IV as per the "New York Heart Association", as these conditions may be affected by the anticholinergic and beta2-agonist mechanism of action. The Product Monograph indicates that Duaklir Genuair should be used with caution in these patients. Accordingly, this is considered a class labelling issue that applies to other LABA/LAMA combinations as well.

A possible interaction between the two active ingredients when administered as a fixed-dose is not of concern given the pharmacokinetic properties of the individual active ingredients. Therefore, while no formal drug interaction studies were conducted with the combined active ingredients, the potential for drug interactions between the two active ingredients is based primarily on the knowledge of the pharmacokinetic properties of each active ingredient, which are included in labelling for Duaklir Genuair.

Based on the evidence supporting the safety and efficacy of Duaklir Genuair provided in this submission, coupled with the history of use (both in Canada and international) of both active ingredients prescribed separately for the treatment management of COPD, Duaklir Genuair is considered to have a favorable risk benefit profile.