Observational study of ivacaftor in people with cystic fibrosis and selected non-G551D gating mutations: final results from VOCAL

Abstract

Background: VOCAL, a phase 4 observational study (NCT02445053), assessed real-world effectiveness of ivacaftor (IVA) in people with CF (pwCF) with ≥1 non-G551D gating mutation (G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P, or G1349D).

Methods: pwCF ≥6 y in IT, NL, and UK who were IVA naive or on IVA ≤18 mo at enrollment were eligible. Data were recorded for 12 mo pre-IVA and up to 48 mo post-enrollment. Continuous outcomes (eg, ppFEV₁, BMI) were assessed from baseline (BL; the last pre-IVA value recorded) in 6-mo intervals up to 48 mo post-IVA using a mixed model for repeated measures; total pulmonary exacerbations (PEx) and healthcare resource utilization (HCRU) post- vs pre-IVA were assessed using a negative binomial model.

Results: 65 of 73 (89%) completed the study; mean IVA exposure was 49.5 mo (range, 2-64). Mean BL age was 26.9 y (SD, 13.5). Mean BL ppFEV₁ (64.83 [SD, 23.61]) increased by a least-squares (LS) mean of 10.77 (SE, 1.28) within 6 mo that was sustained up to 48 mo (10.27 [SE, 1.45]). Mean BL BMI (pwCF ≥20 y, n=49; 22.95 kg/m² [SD, 3.81]) increased by an LS mean of 0.79 (SE, 0.14) within 6 mo and 1.30 (SE, 0.24) at 48 mo. Mean BL BMI z score (pwCF <20 y, n=24; −0.41 [SD, 0.89]) increased by an LS mean of 0.54 (SE, 0.11) within 6 mo and 0.41 (SE, 0.14) at 48 mo. Estimated annualized rates of PEx, PEx requiring hospitalization, all-cause hospitalization, and PEx requiring acute antibiotics decreased by >50% in the first 12 mo post- vs 12 mo pre-IVA, and changes were sustained during treatment. No new safety concerns were identified.

Conclusions: IVA showed sustained effectiveness in clinical outcomes and decreased HCRU.

Sponsor: Vertex