The licensed dose of Bevespi Aerosphere, which contains the long-acting ß2 agonist (LABA) formoterol, and the long-acting antimuscarinic (LAMA) glycopyrronium, is two puffs twice daily, morning and evening. Each actuation provides a delivered dose of formoterol fumarate dihydrate 5 micrograms and glycopyrronium 7.2 micrograms.
The safety and efficacy of Bevespi Aerosphere were assessed in three 24-week randomised controlled trials involving patients with moderate to very severe COPD.
Patients in the Pinnacle-1 (n=2,103), Pinnacle-2 (n=1,615) and Pinnacle-4 studies (n=1,756) were randomised to one of four groups: formoterol/glycopyrronium MDI; glycopyrronium MDI; formoterol MDI; or placebo MDI. The Pinnacle-1 trial also included an open-label tiotropium dry powder inhaler arm.
Effects on lung function
The formoterol/glycopyrronium MDI significantly improved lung function relative to placebo and monocomponent MDIs in all three trials.
At week 24, the differences in change from baseline in morning predose trough FEV1 (the primary end point used in the studies) for formoterol/glycopyrronium MDI versus placebo, glycopyrronium and formoterol MDIs were: 150ml, 59ml and 64ml, respectively, in Pinnacle-1 (all p<0.0001); 103ml, 54ml and 56ml, respectively, in Pinnacle-2 (all p<0.001); and 165ml, 59ml and 72ml, respectively in Pinnacle-4 (all p<0.0001).
In Pinnacle-1, -2 and -4 the formoterol/glycopyrronium combination also provided significant improvements in breathlessness, as measured on the Self-Administered Computerised Transitional Dyspnoea Index (SAC TDI) focal score over 24 weeks compared with placebo and glycopyrronium. In Pinnacle-2 significant improvements compared with formoterol were also observed.
Improvement in disease-specific health-related quality of life, as indicated by a reduction in the St George's Respiratory Questionnaire (SGRQ) total score over 24 weeks, was also observed for formoterol/glycopyrronium MDI versus placebo, formoterol and glycopyrronium MDIs in Pinnacle-1 and -2 and versus placebo and glycopyrronium MDIs in Pinnacle-4.
The combination of formoterol and glycopyrronium was found to have a safety and tolerability profile similar to that of placebo, monocomponent MDIs and open-label tiotropium in Pinnacle-1, -2 and -3. In addition, long-term safety and tolerability was demonstrated in Pinnacle-3, a 28-week extension study of Pinnacle-1 and -2 (n=892). Improvements in efficacy endpoints were also sustained over 52 weeks.