Regulatory Decision Summary for Arnuity Ellipta

Decision issued

A Notice of Noncompliance was issued by Health Canada on August 16, 2018. The company cancelled its submission before a final decision was issued.

Date of cancellation

October 24, 2018

What was the purpose of this submission?

Arnuity Ellipta (fluticasone furoate) is an orally inhaled corticosteroid (ICS) currently indicated for the maintenance treatment of asthma in patients aged 12 years and older. It currently is marketed at doses of 100 and 200 mcg.

The purpose of the current submission was to obtain marketing approval for a 50 mcg dose intended for the maintenance treatment of asthma in pediatric patients aged 5 to 11 years old.

What did the company submit to supports its submission?

To evaluate efficacy of fluticasone furoate 50 mcg in asthmatic patients aged 5 to 11 years old, the Sponsor provided a phase II dose-ranging study (HZA106855), originally designed for the fluticasone furoate/vilanterol pediatric program. This studys primary endpoint was Peak Expiratory Flow (PEF) as opposed to Forced Expiratory Volume in 1 second (FEV1), the latter of which shows less variability and is therefore a more reproducible measurement in evaluating lung function. FEV1 which was a secondary endpoint provided negative results compared to placebo as opposed to the PEF data. This discordance was unexpected as these measurements would be expected to be uniform in direction and magnitude of effect.

The safety profile of fluticasone furoate in pediatric subjects was anticipated to be similar to that observed in adults and adolescents. Additional studies were conducted to evaluate known class effects of ICS treatment in children such as the potential suppressive effects on hypothalamic-pituitary-adrenal (HPA) axis function and growth. These additional studies found no difference between fluticasone furoate 50 mcg and placebo.

What was the status of the submission when it was cancelled? What was Health Canadas assessment of the submission at the time of cancellation?

Due in part to the factors mentioned above, a recommendation for a Notice of Noncompliance (NON) for the Arnuity Ellipta 50 mg dose was made. The NON was issued by Health Canada on August 16, 2018. The Sponsor chose to cancel their submission prior to a 90-day deadline to submit a Response to NON without prejudice to refilling in the future.

What consequences does the cancellation have for patients accessing the drug under the Special Access Programme (SAP), or via clinical trials?

There is no expected impact for patients using SAP or in clinical trials.