PTC Therapeutics, Inc. announced unexpected, yet encouraging results of their product ataluren. The biopharmaceutical company focuses on developing small-molecule drugs that target post-transcriptional control processes to alter protein production. Ataluren is PTC’s investigational new drug designed to restore protein function in cystic fibrosis patients with a nonsense mutation (nmCF) by allowing a complete, functional protein to be synthesized. Nonsense mutations are the cause of cystic fibrosis in 10% of patients.
Michael Konstan, MD, lead study investigator from University Hospitals Rainbow Babies & Children’s Hospital, explained the importance of ataluren in a press release, “Cystic fibrosis patients with nonsense mutations do not produce any functional cystic fibrosis transmembrane conductance regulator (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.”
After putting ataluren through phase 1 and 2 clinical trials, PTC sponsored a randomized, double-blind phase 3 trial that evaluated ataluren against placebo in 238 patients from 36 sites across 11 countries. Success of ataluren treatment was measured using forced expiratory volume in one second (FEV1) assessed by spirometry at baseline and 48 weeks after treatment. Pulmonary exacerbations were used as a secondary outcome measure. All patients, regardless of treatment arm, received treatment three times a day: morning, midday, and evening.
The results were published in The Lancet Respiratory Medicine. FEV1 relative change from baseline was not significantly different between ataluren and placebo-treated patients after 48 weeks, and neither was the number of pulmonary exacerbations. However, when considering patients who were not using chronic inhaled tobramycin, there was a difference in FEV1 and number of pulmonary exacerbations between ataluren- and placebo-treated patients. Patients receiving ataluren experienced an average of only 1.42 events, compared to 2.18 events for patients receiving placebo. Additionally, the safety profile of ataluren remained, with similar adverse events reported among patients.
“The overall data from this trial are promising. 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 aminoglycosides [tobramycin]. Such stabilization of disease is an important clinical endpoint, particularly for this patient population that has one of the most severe forms of cystic fibrosis,” concluded Dr. Konstan.