Regulatory Decision Summary for Trelegy Ellipta

Review decision

The Regulatory Decision Summary explains Health Canada’s decision for the product seeking market authorization. The Regulatory Decision Summary includes the purpose of the submission and the reason for the decision.


Product type:

Drug

Medicinal ingredient(s):

fluticasone furoate, umeclidinium bromide, vilanterol trifenatate

Therapeutic area:

Inhaled corticosteroid; Long-acting muscarinic receptor antagonist; Long-acting beta2 agonist

Type of submission:

Supplement to a New Drug Submission

Control number:

215148
What was the purpose of this submission?

 

This submission proposed to modify the indication to include exacerbation relief along with expanding the intended patient population to all Chronic Obstructive Pulmonary Disease (COPD) patients.

 

Why was the decision issued?

 

Trelegy Ellipta is a triple combination of an inhaled corticosteroid (ICS), a long-acting muscarinic receptor antagonist (LAMA), and a long-acting beta2 agonist (LABA). The product is a fixed-dose combination of Fluticasone Furoate (FF) 100 mcg, Umeclidinium (UMEC) 62.5 mcg, and Vilanterol (VI) 25 mcg for oral inhalation administered via a single Ellipta inhaler. These doses are the same as used in the dual combinations of FF/VI and UMEC/VI, and in UMEC monotherapy, all administered once-daily via the Ellipta inhaler.

The active ingredients of the proposed triple therapy product have been already approved either alone, or in combination, for the treatment of Chronic Obstructive Pulmonary Disease (COPD). The change in indication was based primarily on data from Study CTT116855 (IMPACT trial); a trial that compared FF/UMEC/ VI with FF/VI and UMEC/VI over 52 weeks in subjects with COPD using a primary endpoint of the annual rate of on-treatment moderate/severe exacerbations.

Treatment with Trelegy Ellipta statistically significantly reduced the on-treatment annual rate of moderate/severe exacerbations by 15% compared with the ICS/LABA and by 25% compared with the LAMA/LABA. These results were supported by lung function analysis (as defined by change from baseline through FEV1 at Week 52) and St. Georges Respiratory Questionnaire (SGRQ) score analysis compared to ICS/LABA; time to first moderate/severe exacerbation analysis compared to both ICS/LABA and LAMA/LABA; and rate of severe exacerbations (i.e., requiring hospitalization or resulting in death) compared to LAMA/LABA.

The incidence of pneumonia (adverse events of special interest) was 8% for Trelegy Ellipta, 7% for ICS/LABA, and 5% for LAMA/LABA. Fatal pneumonia occurred in 12 of 4,151 patients (3.5 per 1,000 patient-years) receiving Trelegy Ellipta, 5 of 4,134 patients (1.7 per 1,000 patient-years) receiving ICS/LABA, and 5 of 2,070 patients (2.9 per 1,000 patient-years) receiving LAMA/LABA. Overall, the safety profile of patients in study CTT116855 was similar to patients in study CTT116853.

The comparability of FF/UMEC/VI administered via one inhaler versus multiple devices remains uncertain. Study 200812 did demonstrate non-inferiority between the "open" and "closed" systems as the primary endpoint was statistically significant yet the population pharmacokinetic (PK) analysis (208059) highlighted some differences in FF and UMEC exposure when using one versus multiple inhalers, although these differences are not expected to be clinically relevant. Therefore, data from Study 200812 was not included in the product monograph (PM).

 

Decision issued

Approved; issued a Notice of Compliance in accordance with the Food and Drug Regulations.