Advertisement
(Logo: http://www.newscom.com/cgi-bin/prnh/20010919/PTCLOGO )
Patients with CF lack adequate levels of the CFTR protein, a chloridechannel that maintains proper hydration of epithelial surfaces in the lung,pancreas, and liver. Patients with nonsense-mutation-mediated CF generallyhave a severe form of CF because virtually no CFTR protein is produced.Previous studies of PTC124 adult patients with CF evaluated nasaltransepithelial potential difference (TEPD) as a surrogate for the presenceand activity of the CFTR protein. Across the short- and long-term clinicaltrials at high and low doses of PTC124, TEPD assessments showed statisticallysignificant improvements of mean CFTR-dependent chloride secretion in theairways.
Advertisement
The Phase 2a extension study in Israel assessed 3 months of oral PTC124therapy at two different dose levels in 19 adult men and women with nonsense-mutation-mediated CF who had participated in a prior short-term PTC124 Phase2a study. More than 90% of the patients had chronic CF-related lung infectionand also had CF-induced pancreatic insufficiency. Results from the studyshowed that treatment with PTC124 resulted in statistically significant (p<0.001) improvements in CFTR function as measured by TEPD in both dose groups.The proportion of patients showing improvement in TEPD chloride secretionincreased over time in the extension study. Trends towards improvements inmean FEV1 and FVC values were observed. Baseline data showed that CF patientscough a remarkable 643 times per day on average, with a range of 324 to 1,569coughs per day. In comparison, healthy individuals generally cough fewer than16 times per day, according to the European Respiratory Journal (Hsu 1994).Patients receiving PTC124 experienced a mean [28%] decrease in cough frequencyby the end of three months of therapy (p< 0.01). PTC124 was generally welltolerated, resulting in excellent mean compliance with the treatment regimen (>90%).
"Three months of treatment with PTC124 in nonsense-mutation-mediated CFpatients was associated with time-dependent improvements in nasal TEPDchloride conductance, pulmonary function and cough -- important markerssuggesting the potential for benefit in patients with CF," stated Dr.Wilschanski. "PTC124 increases CFTR-mediated chloride secretion in patientswith a variety of nonsense mutation types, which suggests a broad spectrum ofactivity across one of the major subpopulations in CF."
Dr. Kerem added, "The impact on cough that we observed in this study byobjective measurement is particularly notable given that cough is one of themajor symptomatic manifestations of the underlying disease process in CF. Theredu
