Nonsense Mutations & Cystic Fibrosis
About 10% of CF patients have a nonsense mutation, this equals about 7000 patients in the US & Europe.
How does Ataluren work?
Nonsense mutations have a premature stop codon, which means the ribosome stops making the protein at this point, so the normal protein is not produced.
Occasionally a mistake occurs with the nonsense mutation, where an amino acid is inserted allowing the natural read through past the stop codon. Ataluren exploits this natural phenomenon.
Ataluren acts by binding to the ribosome, which changes the confirmation of the ribosome, promoting read through of the premature stop codon. This enables the production of full length protein.
Previous Phase 3 Trial Results
For those not on inhaled Tobramycin:
+ 5.7% relative improvement in FEV1 after 48 weeks compared to placebo
41% reduction in pulmonary exacerbations compared to placebo
Ataluren Phase 3 Confirmatory Trial
The design will be similar to the previous trial (similar size, dosing). FEV1 will be a primary endpoint and pulmonary exacerbations will be a secondary endpoint. The main difference will be the exclusion of patients who use inhaled Tobramycin. PTC believe that Tobramycin interferes with Ataluren’s mechanism of action, reducing the clinical benefits.
Enrollment to begin in the first half of 2014, will continue for 12-15 months
Trial will run for one year, data expected mid 2016
Previous Phase 3 Trial Results:
Summary of PTC’s Current Research:
Ataluren may help other medical conditions that involve nonsense mutations: