Ataluren is an orally administered, small molecule compound that targets non-sense mutations. It enables the cellular machinery to override the non-sense mutation, allowing the translation process to override the premature stop signal. The investigational drug has restored the production of full-length, functional proteins in preclinical genetic disease models, the company reports.
In cystic fibrosis (CF), an inherited chronic disease that affects the lungs and digestive system of about 70,000 people worldwide, a defective gene and its protein product cause the body to produce unusually thick, sticky mucus that clogs the lungs and leads to life-threatening lung infections, and obstructs the pancreas and stops natural enzymes from helping the body break down and absorb food.
Both Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy, caused by the lack of a protein, progressively weaken the muscles; DMD, the more potent form, confines boys and young men to wheelchairs in their early teens and ultimately affects their breathing and heart functions. While these diseases have no treatments on the market for the underlying cause of the disease, ataluren has the potential to address the underlying cause, Dr. Peltz reports.
Data from Phase IIa clinical trials in cystic fibrosis and DMD demonstrate that treatment with ataluren can restore the production and function of the CFTR and dystrophin protein in some patients with non-sense mutations. The drug has been well tolerated for two to four weeks.
Currently, ataluren is in Phase IIb international pivotal trials in patients with non-sense mutation Duchenne/Becker muscular dystrophy. Clinical trials for ataluren to determine its efficacy in treating CF are planned for later this year.
Results from a Phase IIa European study demonstrated that treatment with ataluren caused statistically significant improvements in the chloride channel function of children with CF caused by a non-sense mutation. In Israel, where the incidence of non-sense-mutation CF is especially high because of its prevalence in Jewish people of Eastern European (Ashkenazic) origin, a 12-week study showed that ataluren was well tolerated.
According to Langdon Miller, M.D., CMO of PTC, “these data demonstrate the activity of ataluren across a broad range of patients and suggest that it could be a valuable option for many patients living with CF. There is, currently, no available therapy to correct defective CFTR production and function. Instead, available treatments for CF are designed to alleviate the symptoms of the disease.”