Achondroplasia (ACH) is the most common form of dwarfism, which currently is with no effective medicinal treatment. Individuals living with ACH may experience diverse and lifelong complications, which may bring great illness burden to themselves, as well as their families and society. ACH is a genetic condition caused by an autosomal dominant activating mutation in fibroblast growth factor receptor 3 (FGFR3) that leads to an imbalance between the fibroblast growth factor receptor 3 (FGFR3) and C-type natriuretic peptide (CNP) signaling pathways，which induces a general inhibition of endochondral bone growth. The global prevalence of the disease is approximately 1 in 25,0001, and 80% of cases are sporadic, occurring in children of their parents with normal stature.
Mortality rates are high in infants with Achondroplasia1. Impaired chondrogenesis and endochondral bone formation lead to a variety of severe skeletal complications and comorbidities. It usually needs to experience several times of surgery to improve the symptoms. All of those make ACH individuals suffer from a low quality of life. Patients may even need special assistance when grown up and it is difficult to integrate themselves into the society1. Currently, there is no effective medicinal product for achondroplasia, the off-label use of recombinant human growth hormone can only increase the final height by 2.8-3.5 cm1.
TransCon CNP is an investigational long-acting prodrug（weekly）of CNP in development for the treatment of ACH in children. It is designed to provide continuous CNP exposure which inhibit the effect of constitutive FGFR3 overactivation 24 hours a day, aiming to promote bone growth and ameliorate and prevent the comorbidities of ACH.
The results of animal experiments showed that TransCon CNP reversed the phenotype, restoring growth, and suggesting potential to ameliorate some of the most disabling achondroplasia traits, including stenosis of the foramen magnum2. A phase 1 trial of TransCon CNP reproduced the pharmacokinetic profile and cardiovascular safety demonstrated in preclinical studies3 and presented TransCon CNP was generally well tolerated without SAE reported nor anti-CNP antibodies detected. TransCon CNP received Orphan Drug Designation (ODD) for the treatment of ACH from the FDA in 2019. A multi-center global phase 2 trial has been initiated.
VISEN Pharma is collaborating with Ascendis and plans to initiate relevant clinical trial in China in 2020.
1.Pauli RM. Orphanet J Rare Dis. 2019;14(1):1-49
2.ENDO 2017 PR:
3.Data on file