Regulatory Decision Summary for Zenhale

Zenhale contains two ingredients, mometasone furoate and formoterol fumarate. Mometasone furoate is a topical glucocorticosteriod with local anti-inflammatory properties. Glucocorticoids, like mometasone furoate, exert their anti-inflammatory effects through glucocorticoid receptors (GRs). Formoterol fumarate is a selective beta2-adrenergic stimulant. It exerts a bronchodilator effect in patients with reversible airway obstruction. It is indicated for the treatment of asthma, in patients 12 years of age and older with reversible obstructive airway disease.

The efficacy of Zenhale in children ages 5-11 years old was demonstrated in a randomized, double-blind, active-controlled, parallel-group, multicenter study in which Zenhale 50 microgram (mcg)/5 mcg (number of subjects (n) = 91) was compared with mometasone furoate metered dose inhaler (MDI) 50 mcg (n = 90), in 181 asthma patients aged 5 to less than 12 years, who had been adequately controlled on an Inhaled Corticosteroid (ICS)/Long-Acting Beta Agonist (LABA) for at least 4 weeks and had no symptoms of asthma worsening during a 2-week run-in on mometasone furoate MDI 100 mcg. Primary endpoint results showed that patients receiving Zenhale 50 mcg/5 mcg had a statistically significant change from baseline to Week 12, compared to mometasone furoate MDI 50 mcg in 60-min AM post-dose percent (%) predicted Forced Expiratory Volume (FEV1) (5.21, p<0.001). In terms of safety, common treatment-emergent adverse events that occurred in patients treated with Zenhale with an incidence of ≥3% and more frequently than patients treated with mometasone furoate alone included influenza, upper respiratory tract infection and headache. Overall, the safety profile for pediatric patients was similar to that observed in patients aged 12 years and older. Based on the result of this trial, the Sponsor’s proposed expanded indication was deemed acceptable by the Therapeutic Products Directorate (TPD).

The modifications to the Indication, Warnings and Precautions, Adverse Reactions and Clinical Trials sections of the Product Monograph (PM) does not alter the benefit-harm-uncertainty assessment of Zenhale and its use remains favorable for the approved indication.