Submitting an NDA despite lacking the full FDA-recommended two-year controlled trial data across different age groups might have been a slightly risky move. But Biomarin Pharmaceutical Inc.’s data supporting the use of Voxzogo (vosoritide) in children with the most common form of dwarfism proved compelling enough for the agency, which cleared the modified C-type natriuretic peptide as the first treatment for the rare genetic disease affecting bone growth.

Voxzogo was approved for children ages 5 and older with achondroplasia and open epiphyses (growth plates), meaning these children still have the potential to grow. There are more than 10,000 children in the U.S. who meet the criteria and about 25% of them have open growth plates.

The approval was based on a double-blind, placebo-controlled, phase III study in which 121 participants were randomly assigned to receive either Voxzogo injections or a placebo. Researchers measured the participants' rate of height growth at the end of the yearlong study. Those children who received Voxzogo grew an average 1.57 cm (six-tenths of an inch) taller than those who received a placebo.

Data from the phase III study, presented at the ENDO21, the Endocrine Society’s annual meeting, showed that children maintained an increase in annual growth velocity (AGV) through the second year of continuous treatment. Children who received two years of Voxzogo had a baseline mean AGV of 4.28 cm (1.68 inches) annually. After one year of treatment, mean AGV was 5.71 cm (2.24 inches) per year and, after the second year, mean AGV was 5.65 cm (2.22 inches) per year. Children also showed improved height z-score, a measure of height relative to that of a similar population of average height.

Voxzogo, an analogue of a C-type natriuretic peptide, is designed to work by directly targeting the underlying pathophysiology of achondroplasia by down-regulating FGFR3 signaling, which, in turn, promotes endochondral bone formation.

Biomarin had a quicker time of it in Europe as Voxzogo received a positive recommendation from the EMA’s Committee for Medicinal Products for Human Use in June 2021, followed two months later by European Commission approval for use of the once-daily injection in children, ages 2 until growth plates are closed.

The list price in France, under a temporary authorization use (ATU), was €712 (US$828) per vial, which translated to an estimated annual per-patient cost of about €260,000 or €300,000. Biomarin said at the time of European approval that it expected the German list price to be consistent with the French ATU price, with those prices subject to material discounts in one to two years following reimbursement negotiations.

The U.S. approval came a day ahead of its original Nov. 20 PDUFA date under an accelerated approval pathway. A condition of the accelerated approval is a post-marketing study will be undertaken to assess final adult height. The application also received priority review designation.

Biomarin opted to provide some additional data – two-year outcomes from the phase III extension study – which pushed the PDUFA date from Aug. 20 to Nov. 20, though the FDA granted the NDA priority review designation. That means the recent nod should result in a priority review voucher.