Podcast: Ataluren and similar compounds (specific therapies for premature termination codon class I mutations) for cystic fibrosis

Cystic fibrosis is an inherited condition, associated with mutation of a specific gene involved in the movement of salt across cells. One of the proposed treatments that targets a particular type of this mutation is a drug called Ataluren, which was the subject of a new Cochrane Review in January 2017. One of the authors, Kevin Southern from the Department of Women's and Children's Health at the University of Liverpool in the UK, describes the available evidence in this podcast.

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John: Hello, I'm John Hilton, editor of the Cochrane Editorial unit. Cystic fibrosis is an inherited condition, associated with mutation of a specific gene involved in the movement of salt across cells. One of the proposed treatments that targets a particular type of this mutation is a drug called Ataluren, which was the subject of a new Cochrane Review in January 2017. One of the authors, Kevin Southern from the Department of Women's and Children's Health at the University of Liverpool in the UK, describes the available evidence in this podcast.

Kevin: Cystic fibrosis, or CF, is a condition common in the European population, leading to lung damage and reduced life expectancy. There are many mutations that can affect the CF gene, some of which are classified as stop codon or nonsense mutations, which have a profound impact on the ability of the gene to manufacture the CF protein. Pre-clinical work has found a number of compounds that may correct this class of mutation and enable production of CF protein. Ataluren is one of these agents that early trials suggest may be of benefit to patients with CF with this particular class of mutation. We wanted to see what the later phase, randomised trials have shown and did our Cochrane Review to find the current evidence on Ataluren and compounds with a similar action. Unfortunately, there is little such evidence at the moment, and the effects of these drugs for patients with CF remain uncertain.
Although we found eight studies that came close to matching our eligibility criteria, only one fulfilled our pre-defined inclusion criteria. This trial was done by the makers of Ataluren, PTC Therapeutics with grant support from the North American CF Foundation. It compared 48 weeks of Ataluren versus placebo in 238 patients over the age of six. At the end of the trial, there was no difference between the treatment groups with respect to quality of life measures or respiratory function. However, patients receiving Ataluren were significantly more likely to have an episode of renal impairment.
An initially unplanned sub-group analysis by the trial investigators suggested a benefit from Ataluren therapy for patients not on nebulised Tobramycin, which is a longterm antibiotic treatment for people with CF. This post-hoc analysis has led to a further randomised trial, for patients not receiving Tobramycin, which started in 2014 and is taking place in North America, Europe and Australasia.
In summary, although there is much interest in the development of fundamental mutation specific therapies for CF, there is insufficient evidence at present to determine the effect of one of these, Ataluren, as a therapy for people with CF who have this particular classification of CF gene mutation.”

John: If you’d like to read more about what evidence there is, you can find the full version of this Cochrane Review at Cochrane Library dot com by searching ‘Ataluren and cystic fibrosis’, which will also be the way to find future updates as more trials become available.

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