Ataluren in cystic fibrosis: development, clinical studies and where are we now?
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| Abstract | INTRODUCTION:
Cystic fibrosis (CF) is one of the most common genetically-acquired life-limiting conditions worldwide. The underlying defect is dysfunction of the cystic fibrosis transmembrane-conductance regulator (CFTR) which leads to progressive lung disease and other multi-system effects. Around 10% of people with CF have a class I nonsense mutation that leads to production of shortened CFTR due to a premature termination codon (PTC). Areas covered: We discuss the discovery of the small-molecule drug ataluren, which in vitro has been shown to allow read-through of PTCs and facilitate synthesis of full-length protein. We review clinical studies that have been performed involving ataluren in CF. Early-phase short-term cross-over studies showed improvement in nasal potential difference. A follow-up phase III randomised controlled trial did not show a significant difference for the primary outcome of lung function, however a post-hoc analysis suggested possible benefit in patients not receiving tobramycin. A further randomised controlled trial in patients not receiving tobramycin has been reported as showing no benefit but has not yet been published in full peer-reviewed form. Expert opinion: A small-molecule approach to facilitate read-through of PTCs in nonsense mutations makes intuitive sense. However, at present there is no high-quality evidence of clinical efficacy for ataluren in people with CF.
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| Authors | Noreen Zainal Abidin, Iram J Haq, Aaron I Gardner, Malcolm Brodlie |
| Journal | Expert opinion on pharmacotherapy (Expert Opin Pharmacother) Vol. 18 Issue 13 Pg. 1363-1371 (Sep 2017) ISSN: 1744-7666 [Electronic] England |
| PMID | 28730885 (Publication Type: Journal Article, Review) |
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