The drug company PTC Therapeutics announced on March 2 that it has discontinued the development of ataluren as a potential treatment for people with cystic fibrosis. Ataluren was an investigational therapy for CF caused by nonsense mutations, which prevent the production of a normal cystic fibrosis transmembrane conductance regulator (CFTR) protein. A dysfunctional or nonexistent CFTR protein disrupts the salt and water balance in the lungs and other tissues and leads to the thick, sticky mucus associated with CF.
The company reported that ataluren did not show significant improvement in lung function or enough of a decrease in exacerbations in its most recent Phase 3 clinical trial. The trial, which began in 2015, was for people with at least one copy of a nonsense mutation who were not taking inhaled aminoglycosides, such as tobramycin.
Cystic Fibrosis Foundation Therapeutics Inc. (CFFT), the nonprofit drug discovery and development affiliate of the Foundation, had provided support for the development of ataluren.
"This result is disappointing for the entire CF community. We stand together until all people with CF have the transformative therapies they need,” said Preston W. Campbell, III, M.D., president and chief executive officer of the Cystic Fibrosis Foundation. “We are aggressively pursuing research into a variety of approaches that may benefit people with nonsense mutations.”
The Foundation is supporting multiple efforts to pursue treatments for the 10 percent of people with CF who have a nonsense, splicing or other rare mutation for which there is no current therapy that targets the root cause of their disease.
CFFT is spearheading a Nonsense and Rare Mutations Research and Therapeutics Initiative, which is expected to grow significantly. The initiative consists of more than 60 collaborative projects with an array of academic programs and pharmaceutical companies around the world.
The initiative includes:
- Screening and development of compounds that would allow the creation of a full-length protein specifically for people with nonsense mutations
- Research into a one-time cure such as gene editing that would benefit all people with CF, including those with rare and nonsense mutations
- Basic scientific research on gene expression, stem cells and gene delivery and repair
Research into nonsense and rare mutations is also ongoing at the recently expanded CFFT research lab, which is focused on identifying candidate therapies for nonsense mutations. Efforts focused on nonsense mutations are also underway through a program led by the nonprofit research organization Southern Research, in collaboration with the University of Alabama (UAB) and CFFT.
CFFT also will hold an international workshop to promote the further development of laboratory cell models to better predict the response of new therapies in people with CF.