Achondroplasia is the most common form of dwarfism for which there is currently no FDA-approved therapy. Achondroplasia results in severe skeletal complications and comorbidities, including narrowing of the foramen magnum, sleep apnea, and chronic ear infections. Individuals with achondroplasia often face multiple surgeries and procedures to alleviate its many complications.
The condition is caused by an autosomal dominant activating mutation in fibroblast growth factor receptor 3 (FGFR3) that leads to an imbalance in the effects of the FGFR3 and C-type natriuretic peptide (CNP) signaling pathways. Preclinical and clinical data show that the CNP pathway stimulates growth; increased CNP counteracts the effects of the FGFR3 mutation downstream, thus promoting bone growth.
TransCon CNP is designed to provide long-term CNP exposure with the goal of optimizing efficacy with a well-tolerated and convenient once weekly dose. A phase 1 trial of TransCon CNP in healthy adult subjects has been completed and reproduced the pharmacokinetic profile and cardiovascular safety from preclinical studies. A phase 2 trial of TransCon CNP in children with achondroplasia is expected to begin in the third quarter of 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.