About PTC124PTC124 represents a first-in-class, orally delivered investigational new drug for the treatment of genetic disorders due to nonsense mutations.
Nonsense mutations are single-point alterations in the genetic code that prematurely halt the translation process, producing a shortened, non- functional protein. In pre-clinical trials, PTC124 allowed the cellular machinery to bypass the nonsense mutation, continue the translation process, and thereby restore the production of a full-length, functional protein.
PTC124 has demonstrated activity in preclinical genetic disease models harboring nonsense mutations. In Phase 1 clinical studies, PTC124 was generally well tolerated, achieved target plasma concentrations that have been associated with activity in preclinical models, and did not induce ribosomal readthrough of normal stop codons. Pharmacokinetic modeling of the Phase 1 results has allowed development of a dosing regimen for the Phase 2 studies in cystic fibrosis (CF) and Duchenne muscular dystrophy (DMD).
It is estimated that 10% of the cases of CF and 15% of the cases of DMD are due to nonsense mutations. In addition to CF and DMD, other potential indications include hemophilia, neurofibromatosis, retinitis pigmentosa, epidermolysis bullosa, and lysosomal storage disorders. PTC124 may represent a unique opportunity to use a single small-molecule drug to address multiple chronic and life- threatening diseases of high unmet medical need. The FDA has granted PTC124 fast-track designation for the treatment of CF and orphan drug designations for the treatment of CF and DMD due to nonsense mutations.
PTC124 has also been granted orphan drug status for the treatment of DMD and CF by the Committee for Orphan Medicinal Products (COMP) of the European Medicines Agency (EMEA). PTC124's development is supported by grants from the Muscular Dystrophy Association (MDA), Cystic Fibrosis Foundation Therapeutics, Inc. (CFFT), FDA's Office of Orphan Products Development (OOPD), and by General Clinical Research Center grants from the National Center for Research Resources (NCRR).