Arnuity Ellipta (fluticasone furoate inhalation powder)

The following drug information is obtained from various newswires, published medical journal articles, and medical conference presentations.

Company:

Approval Status:

Approved August 2014

Specific Treatments:

asthma

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General Information

Arnuity Ellipta contains the active component fluticasone furoate, a synthetic trifluorinated corticosteroid with anti-inflammatory activity.

Arnuity Ellipta is specifically indicated for the once-daily maintenance treatment of asthma as prophylactic therapy in patients aged 12 years and older. Arnuity Ellipta is NOT indicated for the relief of acute bronchospasm. 

Arnuity Ellipta is supplied as a powder for oral inhalation. Arnuity Ellipta should be administered as 1 inhalation once daily by the orally inhaled route. Arnuity Ellipta should be used at the same time every day. Do not use more than 1 time every 24 hours. The starting dosage is based upon patients’ asthma severity. The usual recommended starting dose for patients not on an inhaled corticosteroid is 100 mcg. For other patients, the starting dose should be based on previous asthma drug therapy and disease severity. For patients who do not respond to Arnuity Ellipta 100 mcg after 2 weeks of therapy, replacement with Arnuity Ellipta 200 mcg may provide additional asthma control. The highest recommended daily dose is 200 mcg.

Clinical Results

FDA Approval

The FDA approval of Arnuity Ellipta was based on four confirmatory trials of 3 and 6 months’ duration and three dose-ranging trials of 8 weeks’ duration in 3,611 subjects with asthma.

Dose-ranging trials

Eight doses of fluticasone furoate ranging from 25 to 800 mcg once daily were evaluated in 3 randomized, double-blind, placebo-controlled, 8-week trials in subjects with asthma. Across the 3 trials, subjects were uncontrolled at baseline on treatments of short-acting beta2-agonist and/or non-inhaled corticosteroid controller medications (Trial 687), low-dose inhaled corticosteroid (Trial 685), or medium doses of inhaled corticosteroid (Trial 684). A dose-related increase in trough FEV1 at Week 8 was seen for doses from 25 to 200 mcg with no consistent additional benefit for doses above 200 mcg.  To evaluate dosing frequency, a separate trial compared fluticasone furoate 200 mcg once daily, fluticasone furoate 100 mcg twice daily, fluticasone propionate 100 mcg twice daily, and fluticasone propionate 200 mcg once daily. The results supported the the selection of the once-daily dosing frequency.

Confirmatory Trials

Four confirmatory trials were conducted in adolescent and adult subjects aged 12 years and older with asthma. The trials were designed to evaluate the safety and efficacy of Arnuity Ellipta given once daily in the evening on lung function in subjects who were not controlled on their current treatments of inhaled corticosteroids, or combination therapy consisting of an inhaled corticosteroid plus a LABA. Study treatments were delivered as inhalation powders. The primary endpoint in all trials was change from baseline in evening trough FEV1 measured approximately 24 hours after the final dose of study medication. Trials 2 and 4 had a co=primary endpoint of change from baseline in weighted mean serial FEV1 measured after the final dose of study medication at 5, 15, and 30 minutes and 1, 2, 3, 4, 5, 12, 16, 20, 23, and 24 hours post-dose.

Trial 1: Trial 1 was a 24-week trial that evaluated the efficacy of Arnuity Ellipta 100 mcg compared with placebo on lung function in subjects with asthma. Inhaled fluticasone propionate 250 mcg twice daily was given as a control. Of the 343 enrolled subjects 35% of subjects on placebo and 19% of subjects on Arnuity Ellipta 100 mcg failed to complete the 24-week trial. The mean change from baseline in trough FEV1 was greater among subjects receiving Arnuity Ellipta 100 mcg than among those receiving placebo (mean treatment difference from placebo 146 mL; 95% CI: 36, 257.

Trial 2: Trial 2 was a 12-week trial that evaluated the efficacy of Arnuity Ellipta 100 mcg on lung function in subjects with asthma compared with placebo. The combination of fluticasone furoate 100 mcg and vilanterol 25 mcg was also included as a treatment arm. Of the 609 enrolled subjects, 26% of subjects on placebo and 10% of subjects on Arnuity Ellipta 100 mcg failed to complete the 12-week trial. Arnuity Ellipta 100 mcg once daily had greater mean changes from baseline in trough FEV1 than placebo throughout the trial. At Week 12 or the last available on-treatment visit prior to Week 12, the mean change from baseline in trough FEV1 was greater among subjects receiving Arnuity Ellipta 100 mcg once daily than among those receiving placebo (mean treatment difference 136 mL; 95% CI: 51, 222). Lung function improvements were sustained over the 24-hour period following the final dose of Arnuity Ellipta 100 mcg. Compared with placebo, at Week 12 the change from baseline in weighted mean FEV1 was significantly greater for Arnuity Ellipta 100 mcg (mean treatment difference 186 mL; 95% CI: 62, 310). 

Subjects in both Trials 1 and 2 receiving Arnuity Ellipta 100 mcg once daily had a greater improvement from baseline in percentage of 24-hour periods without need of beta2-agonist rescue medication use than subjects receiving placebo.

Trial 3: Trial 3 was a 24-week trial that evaluated the relative efficacy of Arnuity Ellipta 100 mcg and Arnuity Ellipta 200 mcg on lung function in subjects with asthma. Of the 219 enrolled subjects, 16% on Arnuity Ellipta 100 mcg and 13% of subjects on Arnuity Ellipta 200 mcg failed to complete the 24-week trial. There were trends toward greater mean changes from baseline in the group receiving Arnuity Ellipta 200 mcg than the group receiving Arnuity Ellipta 100 mcg throughout the trial. At Week 24 or the last available on-treatment visit prior to Week 24, the mean change from baseline in trough FEV1 was 208 mL for Arnuity Ellipta 100 mcg, as compared to 284 mL for Arnuity Ellipta 200 mcg (difference of 77 mL; 95% CI: -39, 192). 

Trial 4: Trial 4 was a 24-week trial that evaluated the efficacy of Arnuity Ellipta 200 mcg once daily and fluticasone propionate 500 mcg twice daily on lung function in 586 subjects with asthma. Both Arnuity Ellipta 200 mcg once daily and fluticasone propionate 500 mcg twice daily produced improvement from baseline in lung function. At Week 24 the mean change from baseline in trough FEV1 was 201 mL for Arnuity Ellipta 200 mcg once daily and 183 mL for fluticasone propionate 500 mcg twice daily (treatment difference of 18 mL, 95% CI: -66, 102). Lung function improvements were sustained over the 24-hour period following the final dose of Arnuity Ellipta 200 mcg. At Week 24, the change from baseline in weighted mean FEV1 was 328 mL for Arnuity Ellipta 200 mcg once daily and 258 mL for fluticasone propionate 500 twice daily (difference of 70 mL; 95% CI: -67, 208). 

 

 

Side Effects

Adverse effects associated with the use of Arnuity Ellipta may include, but are not limited to, the following:

  • upper respiratory tract infection
  • nasopharyngitis
  • headache
  • bronchitis

Mechanism of Action

Arnuity Ellipta contains the active component fluticasone furoate, a synthetic trifluorinated corticosteroid with anti-inflammatory activity. The precise mechanism of corticosteroid action on asthma is not known. Inflammation is an important component in the pathogenesis of asthma. Corticosteroids have been shown to have a wide range of actions on multiple cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, lymphocytes) and mediators (e.g., histamine, eicosanoids, leukotrienes, cytokines) involved in inflammation. These anti-inflammatory actions of corticosteroids contribute to their efficacy in asthma. 

Additional Information

For additional information regarding Arnuity Ellipta or asthma, please visit www.gsk.com