Riociguat for the treatment of Phe508del homozygous adults with cystic fibrosis.

BACKGROUND

Riociguat is a first-in-class soluble guanylate cyclase stimulator for which preclinical data suggested improvements in cystic fibrosis transmembrane conductance regulator (CFTR) function.

METHODS

This international, multicenter, two-part, Phase II study of riociguat enrolled adults with cystic fibrosis (CF) homozygous for Phe508del CFTR. Part 1 was a 28-day, randomized, double-blind, placebo-controlled study in participants not receiving CFTR modulator therapy. Twenty-one participants were randomized 1:2 to placebo or oral riociguat (0.5 mg three times daily [tid] for 14 days, increased to 1.0 mg tid for the subsequent 14 days). The primary and secondary efficacy endpoints were change in sweat chloride concentration and percent predicted forced expiratory volume in 1 second (ppFEV

RESULTS

Riociguat did not alter CFTR activity (change in sweat chloride) or lung function (change in ppFEV

CONCLUSIONS

The Rio-CF study was terminated due to lack of efficacy and the changing landscape of CF therapeutic development. The current study⁠, within its limits of a small sample size, did not provide evidence that riociguat could be a valid treatment option for CF.

CLINICAL TRIAL REGISTRATION NUMBER

NCT02170025.

Informations de copyright

Copyright © 2021. Published by Elsevier B.V.

Déclaration de conflit d'intérêts

Declaration of Competing Interest N. Derichs received a speaker honorarium from Vertex Pharmaceuticals, Inc. for participation in a symposium, and served as a consultant for Vertex Pharmaceuticals, Inc. at educational activities and advisory boards. J.L. Taylor-Cousar reports grants paid to her institution from the Cystic Fibrosis Foundation; grants paid to her institution and consulting and speaking fees from Vertex Pharmaceuticals, Inc.; grants paid to her institution from Bayer; grants, consulting, and speaking fees from Celtaxys; grants paid to her institution and consulting fees from Proteostasis Therapeutics, Inc.; consulting fees from Santhera, 4DMT, AbbVie, and Polarean; and grants paid to her institution from Eloxx Pharmaceuticals. J.C. Davies reports grants from the CF Trust and other funding from Algipharma AS, Bayer AG, Boehringer Ingelheim Pharma GmbH & Co. KG, Galapagos NV, ImevaX GmbH, Nivalis Therapeutics, Inc., ProQR Therapeutics III B.V., Proteostasis Therapeutics, Inc., Raptor Pharmaceuticals, Inc., Vertex Pharmaceuticals, Inc., Enterprise, Novartis, Pulmocide, Flatley, Nivalis Therapeutics, Inc., and Teva. I. Fajac received speaker honoraria from Vertex Pharmaceuticals, Inc. for participation in symposia and served as a consultant for Novartis, Proteostasis Therapeutics, Inc., and Vertex Pharmaceuticals, Inc. E. Tullis reports grants paid to her institution from Vertex Pharmaceuticals, Inc., Proteostasis Therapeutics, Bayer AG, Boehringer Ingelheim, AbbVie, Celtaxis, Corbus, and Spyryx, and consultancy fees and honoraria from Vertex Pharmaceuticals, Proteostasis Therapeutics, Astra Zeneca and Horizon. D. Nazareth has nothing to disclose. D.G. Downey reports grants from Vertex Pharmaceuticals, Inc., Proteostasis Therapeutics, Inc., Gilead, and Chiesi; and honoraria or speaker fees from Vertex Pharmaceuticals, Inc., Proteostasis Therapeutics, Inc., and Chiesi. D. Rosenbluth has nothing to disclose. A. Malfroot has nothing to disclose. C. Saunders has nothing to disclose. R. Jensen has nothing to disclose. G.M. Solomon reports work on advisory boards for Bayer and Electromed. F. Vermeulen has nothing to disclose. A. Kaiser is an employee of Bayer AG. S. Willmann is an employee of Bayer AG. S. Saleh is an employee of Bayer AG. K. Droebner is an employee of Bayer AG. P. Sandner is an employee of Bayer AG. C.E. Bear has nothing to disclose. A. Hoffmann is an employee of Bayer AG. F. Ratjen reports other consultancy fees from Vertex Pharmaceuticals, Inc., Bayer, Talecris, CSL Behring, Roche, and Gilead; grants and consultancy from Novartis; and developed speaker bureau for Genentech outside the submitted work. S.M. Rowe reports grants and consulting fees from Arrowhead, Bayer, Celtaxsys, Galapagos/AbbVie, Novartis, Renovion, Synedgen/Synspira, andVertex Pharmaceuticals Inc.; consulting fees from Arcturus, and Cysteic Medicines; and grants from AstraZeneca, Eloxx, N30 Pharmaceuticals, PTC Therapeutics, Translate Bio, and Proteostasis Therapeutics, Inc.