BMN-111: CNP for Achondroplasia

Achondroplasia is the most common form of dwarfism. Achondroplasia is a result of an autosomal dominant mutation in the fibroblast growth factor receptor 3 gene (FGFR3), which causes an abnormality of cartilage and bone formation. In normal circumstances, FGFR3 has a negative regulatory effect on bone growth. In achondroplasia, the mutated form of the receptor is constitutively active and this leads to severely shortened bones. Over 80% of individuals with achondroplasia have parents with normal stature and have achondroplasia as the result of a de novo (spontaneous) gene mutation. Average adult height for men with achondroplasia is 131±5.6 cm; for women, 124±5.9 cm. Incidences have been reported between 1:15,000 to 1:40,000 births.

To counteract the effects caused by the activating FGFR3 mutation, BioMarin has developed a stabilized version of C-type natriuretic peptide (BMN-111), a natural human peptide that is a positive regulator of bone growth. BMN-111 binds to its own receptor which initiates intracellular signals that ultimately inhibit the overactive FGFR3 pathway. Daily subcutaneous injections of BMN-111 in mouse models of the disease have demonstrated the ability of this drug to correct the dwarf phenotype.