Riociguat for the treatment of Phe508del homozygous adults with cystic fibrosis

Nico Derichs; Jennifer L Taylor-Cousar; Jane C Davies; Isabelle Fajac; Elizabeth Tullis; Dilip Nazareth; Damian G Downey; Daniel Rosenbluth; Anne Malfroot; Clare Saunders; Renee Jensen; George M Solomon; Francois Vermeulen; Andreas Kaiser; Stefan Willmann; Soundos Saleh; Karoline Droebner; Peter Sandner; Christine E Bear; Anja Hoffmann; Felix Ratjen; Steven M Rowe; Rio-CF Study Group

doi:10.1016/j.jcf.2021.07.015

Riociguat for the treatment of Phe508del homozygous adults with cystic fibrosis

Nico Derichs, Jennifer L Taylor-Cousar, Jane C Davies, Isabelle Fajac, Elizabeth Tullis, Dilip Nazareth, Damian G Downey, Daniel Rosenbluth, Anne Malfroot, Clare Saunders, Renee Jensen, George M Solomon, Francois Vermeulen, Andreas Kaiser, Stefan Willmann, Soundos Saleh, Karoline Droebner, Peter Sandner, Christine E Bear, Anja HoffmannFelix Ratjen, Steven M Rowe, Rio-CF Study Group

Research output: Contribution to journal › Article › peer-review

5 Citations (Scopus)

30 Downloads (Pure)

Abstract

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 (ppFEV1), respectively, from baseline to Day 14 and Day 28 with riociguat compared with placebo.

RESULTS: Riociguat did not alter CFTR activity (change in sweat chloride) or lung function (change in ppFEV1) at doses up to 1.0 mg tid after 28 days. The most common drug-related adverse event (AE) was headache occurring in three participants (21%); serious AEs occurred in one participant receiving riociguat (7%) and one participant receiving placebo (14%). This safety profile was consistent with the underlying disease and the known safety of riociguat for its approved indications.

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.

Original language	English
Pages (from-to)	1018-1025
Journal	Journal of Cystic Fibrosis
Volume	20
Issue number	6
Early online date	19 Aug 2021
DOIs	https://doi.org/10.1016/j.jcf.2021.07.015
Publication status	Published - Nov 2021

Bibliographical note

Access to Document

10.1016/j.jcf.2021.07.015Licence: CC BY-NC-ND

Riociguat for the treatment of Phe508del homozygous adults with cystic fibrosis
Copyright 2021 the authors. This is an open access article published under a Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits distribution and reproduction for non-commercial purposes, provided the author and source are cited.
Final published version, 878 KBLicence: CC BY-NC-ND

Cite this

Derichs, N., Taylor-Cousar, J. L., Davies, J. C., Fajac, I., Tullis, E., Nazareth, D., Downey, D. G., Rosenbluth, D., Malfroot, A., Saunders, C., Jensen, R., Solomon, G. M., Vermeulen, F., Kaiser, A., Willmann, S., Saleh, S., Droebner, K., Sandner, P., Bear, C. E., ... Rio-CF Study Group (2021). Riociguat for the treatment of Phe508del homozygous adults with cystic fibrosis. Journal of Cystic Fibrosis, 20(6), 1018-1025. https://doi.org/10.1016/j.jcf.2021.07.015

@article{0aba0b219b6d4143a70d193cd26ffef8,

title = "Riociguat for the treatment of Phe508del homozygous adults with cystic fibrosis",

abstract = "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 (ppFEV1), respectively, from baseline to Day 14 and Day 28 with riociguat compared with placebo.RESULTS: Riociguat did not alter CFTR activity (change in sweat chloride) or lung function (change in ppFEV1) at doses up to 1.0 mg tid after 28 days. The most common drug-related adverse event (AE) was headache occurring in three participants (21%); serious AEs occurred in one participant receiving riociguat (7%) and one participant receiving placebo (14%). This safety profile was consistent with the underlying disease and the known safety of riociguat for its approved indications.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.",

author = "Nico Derichs and Taylor-Cousar, {Jennifer L} and Davies, {Jane C} and Isabelle Fajac and Elizabeth Tullis and Dilip Nazareth and Downey, {Damian G} and Daniel Rosenbluth and Anne Malfroot and Clare Saunders and Renee Jensen and Solomon, {George M} and Francois Vermeulen and Andreas Kaiser and Stefan Willmann and Soundos Saleh and Karoline Droebner and Peter Sandner and Bear, {Christine E} and Anja Hoffmann and Felix Ratjen and Rowe, {Steven M} and {Rio-CF Study Group}",

note = "Copyright {\textcopyright} 2021. Published by Elsevier B.V.",

year = "2021",

month = nov,

doi = "10.1016/j.jcf.2021.07.015",

language = "English",

volume = "20",

pages = "1018--1025",

journal = "Journal of Cystic Fibrosis",

issn = "1569-1993",

publisher = "Elsevier Inc.",

number = "6",

}

Derichs, N, Taylor-Cousar, JL, Davies, JC, Fajac, I, Tullis, E, Nazareth, D, Downey, DG, Rosenbluth, D, Malfroot, A, Saunders, C, Jensen, R, Solomon, GM, Vermeulen, F, Kaiser, A, Willmann, S, Saleh, S, Droebner, K, Sandner, P, Bear, CE, Hoffmann, A, Ratjen, F, Rowe, SM & Rio-CF Study Group 2021, 'Riociguat for the treatment of Phe508del homozygous adults with cystic fibrosis', Journal of Cystic Fibrosis, vol. 20, no. 6, pp. 1018-1025. https://doi.org/10.1016/j.jcf.2021.07.015

TY - JOUR

T1 - Riociguat for the treatment of Phe508del homozygous adults with cystic fibrosis

AU - Derichs, Nico

AU - Taylor-Cousar, Jennifer L

AU - Davies, Jane C

AU - Fajac, Isabelle

AU - Tullis, Elizabeth

AU - Nazareth, Dilip

AU - Downey, Damian G

AU - Rosenbluth, Daniel

AU - Malfroot, Anne

AU - Saunders, Clare

AU - Jensen, Renee

AU - Solomon, George M

AU - Vermeulen, Francois

AU - Kaiser, Andreas

AU - Willmann, Stefan

AU - Saleh, Soundos

AU - Droebner, Karoline

AU - Sandner, Peter

AU - Bear, Christine E

AU - Hoffmann, Anja

AU - Ratjen, Felix

AU - Rowe, Steven M

AU - Rio-CF Study Group

PY - 2021/11

Y1 - 2021/11

N2 - 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 (ppFEV1), respectively, from baseline to Day 14 and Day 28 with riociguat compared with placebo.RESULTS: Riociguat did not alter CFTR activity (change in sweat chloride) or lung function (change in ppFEV1) at doses up to 1.0 mg tid after 28 days. The most common drug-related adverse event (AE) was headache occurring in three participants (21%); serious AEs occurred in one participant receiving riociguat (7%) and one participant receiving placebo (14%). This safety profile was consistent with the underlying disease and the known safety of riociguat for its approved indications.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.

AB - 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 (ppFEV1), respectively, from baseline to Day 14 and Day 28 with riociguat compared with placebo.RESULTS: Riociguat did not alter CFTR activity (change in sweat chloride) or lung function (change in ppFEV1) at doses up to 1.0 mg tid after 28 days. The most common drug-related adverse event (AE) was headache occurring in three participants (21%); serious AEs occurred in one participant receiving riociguat (7%) and one participant receiving placebo (14%). This safety profile was consistent with the underlying disease and the known safety of riociguat for its approved indications.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.

U2 - 10.1016/j.jcf.2021.07.015

DO - 10.1016/j.jcf.2021.07.015

M3 - Article

C2 - 34419414

SN - 1569-1993

VL - 20

SP - 1018

EP - 1025

JO - Journal of Cystic Fibrosis

JF - Journal of Cystic Fibrosis

IS - 6

ER -

Riociguat for the treatment of Phe508del homozygous adults with cystic fibrosis

Abstract

Bibliographical note

Access to Document

Fingerprint

Cite this