Vosoritide (BMN 111) for Achondroplasia
Vosoritide is designed for the treatment of achondroplasia, the most common form of dwarfism.
Achondroplasia is the most common form of human dwarfism and is characterized by failure of normal conversion of cartilage into bone, which results in disproportionate short stature. This condition is caused by a mutation in the fibroblast growth factor receptor 3 gene (FGFR3), a negative regulator of bone growth. Disproportionate growth between endochondral bone and underlying organs leads to a number of orthopedic, neurological, respiratory, ear, nose, and throat (ENT) issues and increased mortality.
Beyond disproportionate short stature, people with achondroplasia can experience serious health complications, including foramen magnum compression, sleep apnea, bowed legs, mid-face hypoplasia, permanent sway of the lower back, spinal stenosis, recurrent ear infections and obesity.Some of these complications can result in invasive surgeries such as spinal cord decompression and straightening of bowed legs. Some people with achondroplasia also suffer from chronic pain. Currently there is no FDA-approved treatment for achondroplasia.
To counteract the effects caused by the FGFR3 mutation, BioMarin has developed vosoritide, an investigational drug derived from a natural human peptide that is a positive regulator of bone growth. Vosoritide binds to a specific receptor, which initiates intracellular signals that inhibit the overactive FGFR3 pathway. The investigational treatment is being studied in children with achondroplasia under the age of 18 because their bones are still amenable to growth.
More than 80% of children with achondroplasia have parents of average stature and have the condition as the result of a spontaneous gene mutation. The worldwide incidence rate of achondroplasia is about one in 25,000 live births.
In 2015, BioMarin announced positive Phase 2 proof-of-concept results for vosoritide. Data from the 26 children participating in the Phase 2 study demonstrated a favorable safety profile and efficacy at the 15 micrograms/kilogram/daily dose.