Key Progress Announced for Novel Achondroplasia Treatment

Achondroplasia is a genetic disease that is the leading cause of a type of systemic bone deformation commonly referred to as dwarfism.

California-based BioMarin Pharmaceutical, Inc. recently announced that it has submitted a New Drug Application (NDA) for Vosoritide to the U.S. FDA and that its application to the European Medicines Agency (EMA) has been validated as a treatment for achondroplasia. The drug was previously granted an Orphan Drug designation by both agencies.

Achondroplasia is a disease caused by a mutation in the fibroblast growth factor receptor 3 (FGFR3), normally a negative regulator of bone formation. The mutation results in unregulated activity of FGFR3, resulting in a reduction of chondrocyte activity.

Achondroplasia treatments to date typically involved growth hormone or surgical interventions to correct deformities in the spine and extremities or reduce the risk of hydrocephaly. Spinal cord compression is a major complication and early intervention is critical. Finally, a medical treatment is on the way, potentially helping patients with achondroplasia from ever needing to see the inside of a surgeon’s OR.

The drug, Vosoritide, is administered by subcutaneous injection on a daily basis and contains an analog of C-type Natriuretic Peptide (CNP) that overcomes the activity of FGFR3 allowing for the formation of bone in skeletally immature patients. The form of CNP in Vosoritide has a longer half-life than endogenous CNP allowing for once-daily injections.

The company announced results in December 2019 of a phase 3 study of 121 children who still had active growth plates were given either a placebo or the active treatment for 1 year. A baseline growth rate for each child was established for 6 months prior to treatment. The safety profile was good, with no serious drug-related adverse effects. Any drug-related adverse effects were transient.

“As a treating physician, it is exciting to see these compelling results of an investigational therapy confirming its potential to be the first medical therapy to treat the underlying cause of achondroplasia,” said John A. Phillips, III, M.D., a medical geneticist and the David T. Karzon Professor of Pediatrics at Vanderbilt University Medical Center.

Hank Fuchs, M.D., President of Global Research and Development at BioMarin, thanked the patients and families who participated in the study, as well as the BioMarin team and clinical partners. He described the achievements as, “an important step to bring a treatment where none have [sic] existed before. We also recognize a broad range of views about treatment options, and we look forward to providing children with achondroplasia and their families a treatment choice with this potential new therapy.”

BioMarin specializes in developing drugs for rare genetic diseases such as hemophilia, phenylketonuria (PKU), Batten disease, and multiple types of mucopolysaccharidosis.