GlaxoSmithKline and Innoviva announced top-line results from the Phase 3 FULFIL study, evaluating the closed triple combination therapy fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI 100/62.5/25mcg) for the treatment of chronic obstructive pulmonary disease (COPD). Data was presented at the European Respiratory Society International Congress in London this week.
FULFIL (Lung FUnction and quality of LiFe assessment in COPD with closed trIpLe therapy) was a multicenter, randomized, double-blind, double-dummy, parallel group Phase 3 trial comparing once daily FF/UMEC/VI (100mcg/62.5mcg/ 25mcg) inhalation powder vs. twice daily Symbicort Turbohaler (budesonide/formoterol 400mcg/12mcg) in 1,810 patients with advanced COPD. Co-primary endpoints included the change from baseline in trough FEV1 and St George’s Respiratory Questionnaire (SGRQ) total score after 24 weeks of treatment. Additional endpoints assessed the effect of FF/UMEC/VI on the annual rate of moderate/severe exacerbations and its safety profile compared to budesonide/formoterol over 24 weeks and 52 weeks of treatment.
Analysis of the data showed that the study met its two co-primary endpoints, demonstrating a clinically meaningful and statistically significant (P<0.001) benefit for FF/UMEC/VI in both lung function, measured as mean change from baseline in trough FEV1 (171mL, 95% CI: 148, 194) and health-related quality of life, measured as mean change from baseline in SGRQ total score (-6.6 units for FF/UMEC/VI vs. -4.3 units for budesonide/formoterol, difference of -2.2 units, 95% CI: -3.5, -1). Additionally, patients who received treatment with closed triple therapy for up to 52 weeks achieved a statistically significant improvement of 179mL in trough FEV1 and a numerical improvement of -2.7 units in SGRQ total score at Week 52 vs. budesonide/formoterol.
A statistically significant and clinically meaningful reduction in the annual rate of moderate/severe exacerbations was also achieved with the triple combination therapy, showing a reduction of 35% based on data up to 24 weeks (P=0.002) and 44% up to 52 weeks (P=0.006). The safety profile of FF/UMEC/VI was found to be consistent with the known profile of the individual components and their combinations. The most common adverse events included nasopharyngitis, headache and COPD worsening.
The closed triple therapy is a once daily combination of fluticasone furoate, an inhaled corticosteroid (ICS), umeclidinium, a long-acting muscarinic antagonist (LAMA) and vilanterol, a long-acting beta2-adrenergic agonist (LABA) delivered in GSK’s Ellipta inhaler.