Pneumologie 2018; 72(S 01): S36
DOI: 10.1055/s-0037-1619211
Sektion 7 – Klinische Pneumologie
Posterbegehung – Titel: Asthma II und Mukoviszidose
Georg Thieme Verlag KG Stuttgart · New York

Efficacy and Safety of Tezacaftor/Ivacaftor in Patients Aged >= 12 Years With CF Homozygous for F508del-CFTR: A Randomized Placebo (PBO) -Controlled Phase 3 Trial

S Sutharsan
1   Department of Pulmonary Medicine, University Hospital Essen – Ruhrlandklinik, University Duisburg-Essen
,
J Taylor-Cousar
2   National Jewish Health, CO, USA
,
J Lekstrom-Himes
3   Vertex Pharmaceuticals Incorporated, MA, USA
,
L Wang
3   Vertex Pharmaceuticals Incorporated, MA, USA
,
Y Lu
3   Vertex Pharmaceuticals Incorporated, MA, USA
,
JS Elborn
4   Imperial College and Royal Brompton Hospital, London, UK
› Author Affiliations
Further Information

Publication History

Publication Date:
21 February 2018 (online)

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Objective:

To evaluate efficacy and safety of tezacaftor (VX-661)/ivacaftor combination therapy (TEZ/IVA) in pts with CF aged ≥12 y homozygous for F508del-CFTR.

Methods:

Pts received TEZ 100 mg qd/IVA 150 mg q12h or PBO for 24 wks. Primary endpoint was absolute change in ppFEV1 from baseline (BL) through wk 24 (NCT02347657). Key secondary endpoints were relative change in ppFEV1 and number of pulmonary exacerbations (PEx) through wk 24, absolute change in BMI at wk 24, and absolute change in CFQ-R respiratory domain score through wk 24. Key efficacy endpoints were analyzed sequentially. Change in sweat chloride (SwCl) from BL through wk 24 was assessed. Safety was a secondary objective.

Results:

509 pts received ≥1 dose of TEZ/IVA (n = 251) or PBO (n = 258). BL characteristics were well balanced. A significant treatment effect favored TEZ/IVA in absolute change in ppFEV1 from BL through wk 24 (4.0 percentage points [95% CI: 3.1, 4.8]; P< 0.0001), including in pts with ppFEV1 < 40 at BL (TEZ/IVA [n = 24] vs. PBO [n = 23]: 3.5 percentage points [1.0, 6.1]). Treatment differences for relative change in ppFEV1 (%) (6.8 [5.3, 8.3]; P< 0.0001) and PEx (event rate, 0.64 vs. 0.99; P= 0.0054) met statistical significance; change in BMI did not (0.06 kg/m2 [-0.08, 0.19]; P= 0.4127). Effects favoring TEZ/IVA in CFQ-R (5.1 [3.2, 7.0]) and SwCl (-10.1 mmol/L [-11.4, -8.8]) were nominally significant. Most treatment-emergent adverse events (AEs) were mild (TEZ/IVA 45.4% vs. PBO 38.4%) or moderate (36.3% vs. 45.3%); the most common were infective PEx (29.9% vs. 37.2%), cough (26.3% vs. 32.6%), headache (17.5% vs. 14.3%), nasopharyngitis (16.7% vs. 15.1%), and sputum increased (14.3% vs. 16.3%). Predefined respiratory events occurred in 13.1% (TEZ/IVA) and 15.9% (PBO) of pts. Discontinuations due to AEs occurred in 2.8% (TEZ/IVA) and 3.1% (PBO) of pts; none were due to respiratory events. Serious AEs occurred in 12.4% (TEZ/IVA) and 18.2% (PBO) of pts; no deaths occurred.

Conclusions:

Significant improvements in ppFEV1, PEx rate, CFQ-R (nominal), and SwCl (nominal) were observed with 24 wks of TEZ/IVA vs. PBO. Treatment was well tolerated with few discontinuations. Incidence of respiratory events was similar between PBO and TEZ/IVA; none led to treatment discontinuation. Results support efficacy and safety of TEZ/IVA in pts with CF homozygous for F508del-CFTR.