New LABA/LAMA combination inhaler increases choice for COPD patients

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.

Clinical studies

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).

Symptomatic outcomes

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.

Safety profile

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.