FDA Approves Expanded Use of BioMarin’s Voxzogo to Children of All Ages with Achondroplasia

Rare Daily Staff

The U.S. Food and Drug Administration has approved the supplemental New Drug Application for BioMarin Pharmaceutical’s Voxzogo to increase linear growth in pediatric patients with achondroplasia with open growth plates.

This indication is approved under accelerated approval based on an improvement in annualized growth velocity. Previously, Voxzogo was indicated for children who were 5 years of age and older. The expanded indication now includes children of all ages with open growth plates.

Voxzogo is the only approved treatment for children with achondroplasia, the most common form of skeletal dysplasia leading to disproportionate short stature in humans. It is characterized by slowing of endochondral ossification, which results in disproportionate short stature and disordered architecture in the long bones, spine, face, and base of the skull. This condition is caused by a change in the FGFR3 gene, a negative regulator of bone growth. Voxzogo, a C-type natriuretic peptide analog, acts as a positive regulator of the signaling pathway downstream of FGFR3 to promote endochondral bone growth.

More than 80 percent 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. Voxzogo is being tested in children whose growth plates are still “open,” typically those under 18 years of age. Approximately 25 percent of people with achondroplasia fall into this category. In children with achondroplasia, endochondral bone growth, an essential process by which bone tissue is created, is negatively regulated due to a gain of function mutation in FGFR3.

“We look forward to further understanding the potential role of Voxzogo in other genetic short stature conditions, including hypochondroplasia.” said Hank Fuchs, president of Worldwide Research and Development at BioMarin.

BioMarin conducted a randomized, double-blind, placebo-controlled phase 2 clinical trial evaluating the safety and efficacy of Voxzogo in children aged 5 and under. Based on the results of this trial, together with evidence from the adequate and well controlled phase 3 study in pediatric patients aged 5 years and older, the safety and effectiveness of Voxzogo have been established in pediatric patients of all ages for the improvement in linear growth in children with achondroplasia with open epiphyses (growth plates). The overall safety profile of Voxzogo in children under 5 years of age was similar to that seen in older children.

Data from an open-label, long-term phase 2 extension study was recently presented at the 2023 European Society for Paediatric Endocrinology Meeting in September. Over a four-year period, children aged 2 years and above who received Voxzogo exhibited a mean height Z-score improvement of 1.1 to 1.4 standard deviations and a mean height gain of 6.3 to 7.8 cm when compared to untreated children with achondroplasia of the same age and sex. In addition, children under the age of 2 years, treated with Voxzogo for three years, had a mean height Z-score improvement of 0.8 to 1.0 standard deviations and a height gain between 3.5 and 3.9 cm.

Voxzogo is approved in the United States and indicated to increase linear growth in children with achondroplasia with open epiphyses. This indication is approved under accelerated approval based on an improvement in annualized growth velocity. Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trial or trials. To fulfill this post-marketing requirement, BioMarin intends to use the ongoing open-label extension studies compared to available natural history.

Voxzogo is currently approved in Europe in children with achondroplasia who are 2 years of age and older with open growth plates. In September, the European Medicines Agency’s Committee for Medicinal Products for Human Use adopted a positive opinion recommending marketing authorization to expand the indication for Voxzogo for injection to treat children with achondroplasia aged 4 months and older whose epiphyses are not closed. A final approval decision, typically consistent with the CHMP recommendation, is expected from the European Commission later this year.

Voxzogo is also approved in Japan in children from birth who have achondroplasia with open growth plates. In addition, it is approved in Brazil in children who are 6 months and older with open growth plates as well as in Australia in children with achondroplasia who are 2 years of age and older with open growth plates.

Photo: Hank Fuchs, president of Worldwide Research and Development at BioMarin