PTC Therapeutics, Inc. has announced the results of a Phase-3 study of ataluren to treat patients with nonsense mutation cystic fibrosis (nmCF). The article was recently published in Lancet Respiratory Medicine. The results demonstrated positive effects in lung function, which was set by investigators as the primary endpoint, and measured by %-predicted FEV1 (forced expiratory volume in 1 second). In addition, ataluren reduced the rate of pulmonary exacerbations, which was the study’s secondary outcome.
“The overall data from this trial are promising,” said Michael Konstan, M.D., lead study investigator from University Hospitals Rainbow Babies and Children’s Hospital in Cleveland, Ohio. “Patients on ataluren experienced fewer pulmonary exacerbations and showed a stabilization in their FEV1 results, particularly in the subgroup of patients that did not use chronic inhaled amino glycosides. Such stabilization of disease is an important clinical endpoint, particularly for this patient population that has one of the most severe forms of CF. CF patients with nonsense mutations do not produce any functional CFTR protein and therefore generally have a more severe form of cystic fibrosis. Current treatments for nonsense mutation cystic fibrosis focus on alleviating symptoms and reducing infections, whereas ataluren targets the underlying cause of disease.”
According to a company press release, in the Phase-3 study, which was designed to be both double-blinded and placebo-controlled in order to achieve the quality data results, 238 nm CF patients at 36 sites in 11 countries throughout North America and Europe were enrolled, receiving either ataluren (n=116) or placebo (n=116) for 48 weeks. %-predicted FEV1 was measured every 8 weeks for up to 48 weeks during treatment.
The results revealed that the relative change from baseline in %-predicted FEV1 across all post-baseline study visits were 2.5% less in the ataluren-group than in the placebo-group (-1.8% average change on ataluren, -4.3% average change on placebo; p=0.048). 23% fewer pulmonary exacerbations were observed in the ataluren-group compared to placebo-group (p=0.0992).
The post hoc analysis was conducted in the subgroup of patients who were not receiving chronic inhaled tobramycin. They found that the mean change of % predicted FEV1 from baseline was -0.7% in patients received ataluren, while -6.4% in patients received placebo (nominal p=0.0082). In addition, ataluren-treated patients experienced 40% fewer exacerbations in the subgroup. These results supports the hypothesis that inhaled tobramycin may interfere with ataluren.
Ataluren was generally well tolerated in the study: the overall incidence of adverse events through 48 weeks was similar in the ataluren group and placebo group, and most adverse events were of mild or moderate severity. No life-threatening adverse events were reported. 8 patients in the ataluren group and 3 patients in the placebo group discontinued treatment due to adverse events.