US-based biopharmaceutical firm PTC Therapeutics has reported results of a Phase III double-blind, placebo-controlled trial of ataluren in patients with nonsense mutation cystic fibrosis (nmCF).
Results showed positive trends in both the primary endpoint, lung function as measured by relative change in percent predicted FEV1 (forced expiratory volume in one second), as well as in the secondary outcome measure, rate of pulmonary exacerbations.
Combined data from the trial, including retrospective and subgroup analyses support the conclusion that ataluren was active and showed clinically meaningful improvements over placebo.
University Hospitals Rainbow Babies and Children's Hospital in Cleveland lead study investigator Michael Konstan said the overall data from this trial are promising.
"Patients on ataluren experienced fewer pulmonary exacerbations and showed a stabilisation in their FEV1 results, particularly in the subgroup of patients that did not use chronic inhaled aminoglycosides," Konstan said.
"Such stabilisation 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."
A total of 238 nmCF patients, aged six years and older, were enrolled in the 48-week trial, which was carried out at 36 sites in 11 countries in North America and Europe.
Its primary endpoint showed a positive trend favouring ataluren versus placebo, and a larger effect in patients not receiving chronic inhaled tobramycin.
The primary endpointwas the relative change in percentage predicted FEV1 from baseline to Week 48 as assessed by spirometry, which was performed at screening, at randomisation, and every eight weeks during the 48 week study duration.
The secondary objective was rate of pulmonary exacerbations, while additional endpoints assessed other aspects of patient function, drug activity, and safety.
In the trial, patients were randomly assigned to one of two treatment arms: ataluren (10mg/kg morning, 10mg/kg midday, 20mg/kg evening) or placebo (morning, midday, evening).
The company said that patients who completed the trial were eligible to receive open-label ataluren in an ongoing extension trial.
PTC Therapeutics chief executive officer Stuart Peltz said: "Given spirometry and pulmonary exacerbation results in the subgroup of patients not receiving chronic inhaled tobramycin, and a favorable safety profile, this study supports further clinical testing of ataluren as a potential first-in-class treatment for nmCF patients not receiving chronic inhaled tobramycin."