Breo Ellipta (fluticasone furoate and vilanterol) - 2 Indications

Scroll down for more information on each indication:

• for the treatment of chronic obstructive pulmonary disease; approved May 2013
• for the once-daily treatment of asthma in patients aged 18 years and older; approved April 2015

General Information

Breo Ellipta is a combination of fluticasone furoate, an inhaled corticosteroid (ICS), and vilanterol, a long-acting beta2-adrenergic agonist (LABA).

BreoEllipta is specifically indicated for:

• the long-term, once-daily, maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema. Breo Ellipta is also indicated to reduce exacerbations of COPD in patients with a history of exacerbations.
• Once-daily treatment of asthma in patients aged 18 years and older

Breo Ellipta is supplied as a powder for inhalation. Scroll down for the recommended dosing/administration for each indication.

Mechanism of Action

Breo Ellipta is a combination of fluticasone furoate, an inhaled corticosteroid (ICS), and vilanterol, a long-acting beta2-adrenergic agonist (LABA).

Side Effects

COPD: Most common adverse reactions (incidence ≥3%) are nasopharyngitis, upper respiratory tract infection, headache, oral candidiasis, back pain, pneumonia, bronchitis, sinusitis, cough, oropharyngeal pain, arthralgia, hypertension, influenza, pharyngitis, and pyrexia.

Asthma: Most common adverse reactions (incidence ≥2%) are nasopharyngitis, oral candidiasis, headache, influenza, upper respiratory tract infection, bronchitis, sinusitis, oropharyngeal pain, dysphonia, and cough

Indication 1 - for the treatment of chronic obstructive pulmonary disease

approved May 2013

Dosing/Administration

Breo Ellipta 100/25 should be administered as 1 inhalation once daily. The maximum recommended dosage is 1 inhalation once daily, the only strength indicated for the treatment of COPD. If shortness of breath occurs in the period between doses, an inhaled, short-acting beta2-agonist (rescue medicine, e.g., albuterol) should be taken for immediate relief.

Clinical Results

The FDA approval was based on 4 confirmatory trials of 6- and 12-months’ duration, three 12-week active comparator trials, and dose-ranging trials of shorter duration.
Dose-Ranging Trials
Vilanterol: Dose selection for vilanterol in COPD was supported by a 28-day, randomized, double-blind, placebo-controlled, parallel-group trial evaluating 5 doses of vilanterol (3 to 50 mcg) or placebo dosed in the morning in 602 patients with COPD. Results demonstrated dose-related increases in FEV1 compared with placebo at Day 1 and Day 28 . These results supported the evaluation of vilanterol 25 mcg in the confirmatory COPD trials. Fluticasone furoate: 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. 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 twice-daily. The results supported the selection of the once-daily dosing frequency. Based on the dose-ranging trials in asthma and COPD, once-daily doses of fluticasone furoate/vilanterol 50 mcg/25 mcg, 100 mcg/25 mcg, and 200 mcg/25 mcg were evaluated in the confirmatory COPD trials.
Confirmatory Trials
Four confirmatory trials in subjects with COPD were designed to evaluate the efficacy of Breo Ellipta on lung function (Trials 1 and 2) and exacerbations (Trials 3 and 4).
Trials 1 and 2: Lung Function
These 24-week, randomized, double-blind, placebo-controlled trials enrolled 2,254 subjects. In Trial 1, subjects were randomized to Breo Ellipta 100 mcg/25 mcg, fluticasone furoate/vilanterol 200 mcg/25 mcg, fluticasone furoate 100 mcg, fluticasone furoate 200 mcg, vilanterol 25 mcg, and placebo. In Trial 2, subjects were randomized to Breo Ellipta 100 mcg/25 mcg, fluticasone furoate/vilanterol 50 mcg/25 mcg, fluticasone furoate 100 mcg, vilanterol 25 mcg, and placebo. All treatments were administered as 1 inhalation once daily. The co-primary efficacy variables in both trials were weighted mean FEV1 (0 to 4 hours) postdose on Day 168 and change from baseline in trough FEV1 on Day 169 (the mean of the FEV1 values obtained 23 and 24 hours after the final dose on Day 168). Breo Ellipta 100 mcg/25 mcg demonstrated a larger increase in the weighted mean FEV1 (0 to 4 hours) relative to placebo and fluticasone furoate 100 mcg at Day 168. At Day 169, both Trials 1 and 2 demonstrated significant increases in trough FEV1 for all strengths of the fluticasone furoate/vilanterol combination compared with placebo.

Indication 2 - for the once-daily treatment of asthma in patients aged 18 years and older

approved April 2015

Dosing/Administration

The recommended starting dosage is Breo Ellipta 100/25 or Breo Ellipta 200/25 administered as 1 inhalation once daily. When choosing the starting dosage strength of Breo Ellipta, consider the patients’ disease severity, based on their previous asthma therapy, including the ICS dosage, as well as the patients’ current control of asthma symptoms and risk of future exacerbation. The maximum recommended dosage is 1 inhalation of Breo Ellipta 200/25 once daily.

Clinical Trial Results

The efficacy of Breo Ellipta was evaluated in 4 randomized, double-blind, parallel-group clinical trials in adult and adolescent subjects with asthma. Three (3) trials were designed to evaluate the safety and efficacy of Breo Ellipta given once daily in subjects who were not controlled on their current treatments of ICS or combination therapy consisting of an ICS plus a LABA (Trials 1, 2, and 3). A 24- to 76-week exacerbation trial was designed to demonstrate that treatment with Breo Ellipta 100/25 significantly decreased the risk of asthma exacerbations as measured by time to first asthma exacerbation when compared with fluticasone furoate 100 mcg (Trial 5). This trial enrolled subjects who had 1 or more asthma exacerbations in the year prior to trial entry.