Regulatory Decision Summary for Arnuity Ellipta

The clinical efficacy and safety of Arnuity Ellipta (fluticasone furoate) once daily was evaluated in four pivotal multicentre, randomized, double blind, parallel-group clinical studies of between 12 and 24 weeks in duration in patients aged 12 years and older with persistent asthma. The primary objective of these studies was to evaluate the efficacy and safety of Arnuity Ellipta (inhaled fluticasone furoate) 100 µg or 200 µg administered once daily compared with either placebo or active comparator [fluticasone propionate (FP) 250 µg twice a day (BD) or FP 500 µg BD). The primary endpoint in all pivotal studies was the change from baseline in evening trough Forced Expiratory Volume in 1 second (FEV₁) measured approximately 24 hours after the final dose of study medication. Two studies also had a co-primary endpoint of change from baseline in weighted mean serial FEV₁ measured after the final dose of study medication at different time points post-dose.

The efficacy of Arnuity Ellipta 100 µg once daily on lung function was compared with placebo in two pivotal studies. In the 24 week study, the change from baseline in trough FEV₁ was significantly greater for Arnuity Ellipta 100 µg once-daily [146 mL, 95% confidence interval (CI) 36, 257, p = 0.009] compared with placebo. Similarly, in the 12 week study, the change from baseline in trough FEV₁ for Arnuity Ellipta 100 µg once-daily was significantly greater than placebo (136 mL, 95% CI: 51, 222, p = 0.002). Overall, results of secondary efficacy endpoints, including changes from baseline in percentage of 24-hour periods without the need of beta2-agonist rescue medication use, support the results of the primary efficacy endpoint.

The efficacy of Arnuity Ellipta 200 µg once daily on lung function was compared with Arnuity Ellipta 100 µg in one study and fluticasone propionate (FP) 500 µg BD in an another study. Patients receiving Arnuity Ellipta 200 µg generally had numerically greater changes from baseline in trough FEV₁ than patients receiving Arnuity Ellipta 100 µg throughout the study. At Week 24, the change from baseline in trough FEV₁ was 208 mL for Arnuity Ellipta 100 µg and 284 mL for Arnuity Ellipta 200 µg, a difference of 77 mL (95% CI: -39, 192). When compared with FP 500 µg BD, the improvements from baseline in lung function were similar for Arnuity Ellipta 200 µg once-daily. At Week 24, the change from baseline in trough FEV₁ was 201 mL for Arnuity Ellipta 200 µg once-daily and 183 mL for FP 500 µg BD (treatment difference of 18 mL; 95% CI: -66, 102).

One uncertainty regarding the efficacy of Arnuity Ellipta (fluticasone furoate) includes its long term effect on lung function and its effect on asthma symptoms.

The most common adverse events (AEs) associated with treatment with Arnuity Ellipta include nasopharyngitis, bronchitis, upper respiratory tract infection, sinusitis, pharyngitis, influenza, respiratory tract infection viral, oral candidiasis, rhinitis, oropharyngeal candidiasis, gastroenteritis, cystitis, oropharyngeal pain, cough, dysphonia, rhinitis allergic, nasal congestion, respiratory disorder, headache, toothache, abdominal pain, abdominal pain upper, diarrhea, procedural pain, back pain, and hypertension. The most common drug-related AEs reported were dysphonia, oral candidiasis, headache, oropharyngeal candidiasis, upper respiratory tract infection, bronchitis, and cough. Overall, the safety profile of Arnuity Ellipta (fluticasone furoate) is generally consistent with the known class effects of an inhaled corticosteroid.

Uncertainties regarding the safety of Arnuity Ellipta (fluticasone furoate) include:

1. long-term safety beyond one year of use, in particular in adolescent asthmatic patients treated with Arnuity Ellipta 200 µg;
2. use in pregnant or breast-feeding women;
3. risk of pneumonia in patients with asthma; and
4. effect of growth retardation in children between 12 and 17 years of age.

Arnuity Ellipta (fluticasone furoate) is indicated for the once-daily maintenance treatment of steroid-responsive bronchial asthma in patients aged 12 years and older. It is not indicated for the relief of acute bronchospasm, and the safety and efficacy of Arnuity Ellipta have not been established in children less than 12 years of age.

In conclusion, the evidence submitted in this NDS supports the safety and efficacy of Arnuity Ellipta (fluticasone furoate) for the recommended indication and dosage administration. The risk-benefit profile of Arnuity Ellipta is considered favourable.