Achondroplasia (ACH) is the most common form of dwarfism for which there is currently no FDA-approved therapy. Individuals living with ACH may experience severe complications and comorbidities. For example, abnormal development of the bone can lead to chronic back and leg pain from lower spine impingement and sleep apnea with risk of sudden infant death from cervical medullary compression. Chronic ear infections due to abnormal eustachian tubes can lead to hearing loss and speech delay.
ACH is a genetic condition caused by an autosomal dominant activating mutation in fibroblast growth factor receptor 3 (FGFR3) that leads to an imbalance in the effects of the fibroblast growth factor (FGF) and C-type natriuretic peptide (CNP) signaling pathways. Preclinical and clinical data show that the CNP pathway stimulates growth and increased CNP counteracts the abnormal effects of the FGFR3 mutation downstream, thus promoting bone growth.
TransCon CNP is an investigational long-acting prodrug of CNP in development for the treatment of ACH in children. It is designed to provide continuous CNP exposure with the goal of optimizing efficacy with a safe and convenient once-weekly dose. A phase 1 trial of TransCon CNP in healthy adult subjects was completed; the results confirmed the pharmacokinetic profile and cardiovascular safety demonstrated in preclinical studies. We are now conducting the ACcomplisH Trial, a global phase 2 trial to evaluate the safety and efficacy of TransCon CNP in children with achondroplasia.
TransCon CNP received Orphan Drug Designation (ODD) for the treatment of ACH from the FDA in 2019.
Achondroplasia is the most common form of human dwarfism. It is a skeletal disease characterized by an average-size trunk and short limbs. In patients with this condition, disproportionate growth between endochondral bone and underlying organs can lead to a number of orthopedic, neurological, respiratory, ear, nose and throat (ENT) and dental issues. Spinal stenosis, foramen magnum stenosis, ear infections, scoliosis and joint problems are common.