Long-Term Ivacaftor in People Aged 6 Years and Older with Cystic Fibrosis with Ivacaftor-Responsive Mutations
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ORIGINAL RESEARCH
Long-Term Ivacaftor in People Aged 6 Years and Older with Cystic Fibrosis with Ivacaftor-Responsive Mutations Joseph M. Pilewski . Kris De Boeck . Jerry A. Nick . Simon Tian . Cynthia DeSouza . Mark Higgins . Richard B. Moss
Received: July 28, 2020 Ó The Author(s) 2020
ABSTRACT Introduction: Mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR) affect the quantity and/or function of Digital Features To view digital features for this article go to https://doi.org/10.6084/m9.figshare.12841538.
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s41030020-00129-2) contains supplementary material, which is available to authorized users. J. M. Pilewski (&) University of Pittsburgh, UPMC Montefiore Hospital, NW628, 3459 Fifth Ave, Pittsburgh, PA 15213, USA e-mail: [email protected] K. De Boeck Faculty of Medicine, University Hospital of Leuven, Herestraat 49, 3000 Leuven, Belgium J. A. Nick National Jewish Health, 1400 Jackson St, Denver, CO 80206, USA S. Tian C. DeSouza Vertex Pharmaceuticals Incorporated, 50 Northern Ave, Boston, MA 02210, USA M. Higgins Vertex Pharmaceuticals (Europe) Limited, 2 Kingdom St, London W2 6BD, UK R. B. Moss Center of Excellence in Pulmonary Biology, Stanford University School of Medicine, 770 Welch Rd #350, Palo Alto, CA 94304, USA
CFTR protein reaching the cell surface. Ivacaftor, a CFTR potentiator that enhances chloride transport, increases the channel-open probability of normal and dysfunctional CFTR. Initially approved for people with CF (pwCF) with G551D-CFTR gating mutations, ivacaftor demonstrated clinical benefit in pwCF with other gating mutations and certain residual function mutations, including R117H-CFTR, in clinical studies. We evaluated the long-term safety and efficacy of ivacaftor in pwCF aged 6 years and older with non-G551D-CFTR ivacaftor-responsive mutations. Methods: Efficacy and safety data from a phase 3, multicenter, open-label, extension study for participants from Study 110 (R117H-CFTR mutations), Study 111 (non–G551D-CFTR gating mutations), and Study 113 (n-of-1 pilot study in participants with residual CFTR function) were analyzed. Following washout from the randomized parent study, participants received oral ivacaftor 150 mg once every 12 h for 104 weeks. Results: Forty-one of 121 participants completed treatment through 104 weeks; 59 participants who did not complete the extension study continued treatment with commercial ivacaftor. The most common adverse events were pulmonary exacerbation (46.3%) and cough (33.9%). Most treatment-emergent adverse events were mild/moderate in severity and consistent with manifestations of CF or the ivacaftor safety profile. Rapid, durable
Pulm Ther
improvement occurred across all efficacy endpoints. Conclusions: Ivacaftor was generally safe and well tolerated with no new safety concerns for up to 104 weeks in pwCF with ivacaftor-responsive mutations. The pattern of improvement across efficacy endpoints was durable and generally
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