BioMarin to Present Long-Term Data on Achondroplasia Drug, New Data on Hypochondroplasia

Rare Daily Staff

BioMarin said researchers will present positive results from an investigator-sponsored study of its drug Voxzogo in children with hypochondroplasia and new, seven-year data that demonstrates the medicine’s positive impact on quality of life in children with achondroplasia.

The results will be presented at the American College of Medical Genetics and Genomics Annual Clinical Genetics Meeting in Toronto this week.

Achondroplasia, the most common form of skeletal dysplasia leading to disproportionate short stature in humans, 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.

Hypochondroplasia is a related condition. It too is caused by a mutation in the FGFR3 gene. In the case of hypochondroplasia, bones grow slower and are shorter than typical.

Voxzogo, a C-type natriuretic peptide (CNP) analog, acts as a positive regulator of the signaling pathway downstream of FGFR3 to promote endochondral bone growth. 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. BioMarin is conducting ongoing open-label extension studies compared to available natural history to confirm the drug’s clinical benefits.

Andrew Dauber, lead study author and chief of endocrinology at Children’s National Hospital in Washington, D.C., will present results from his investigator-sponsored phase 2 study of Voxzogo in children with hypochondroplasia. The annualized growth velocity increased from 5.12 cm/year during the observation period to 6.93 cm/year during the treatment period. No new safety signals were reported.

“We are encouraged by preliminary results from the first study evaluating Voxzogo in children with hypochondroplasia, suggesting the medicine has the potential to impact growth outcomes for this group of patients,” said Dauber. “There are currently no approved medicines for children with hypochondroplasia, so we look forward to gathering additional data to deepen our understanding of Voxzogo in hypochondroplasia and other growth-related conditions.”

In late 2023, BioMarin launched the pivotal clinical trial program studying the safety and efficacy of Voxzogo in children with hypochondroplasia. A multinational observational study in children with hypochondroplasia is currently recruiting participants, and the company plans to enter the treatment phase later this year.

Separately, data from two studies of Voxzogo in children 5 years of age and older with achondroplasia demonstrated a sustained improvement in annualized growth velocity for each year that the participants were treated. In the phase 2 study with more than 7 years of follow up, the mean increase in growth across each year of age up to 16 years compared with untreated participants was 1.63 cm/year for boys and 1.33 cm/year for girls.

Separate cross-sectional comparative analysis assessing increase in height over a 7-year period showed an additional height gain of 11.03 cm with use of Voxzogo compared to matched untreated children over the same period.

The same analyses were produced for the phase 3 trial in which children with achondroplasia have a mean treatment follow-up of four years. It showed the mean increase in growth across each year of age up to 17 years was 1.73 cm/year for boys and 1.46 cm/year for girls. A separate cross-sectional comparative analysis assessing increase in height over a three-year period showed an additional height gain of 5.75 cm with use of Voxzogo compared to matched untreated children over the same period.

Results from a separate analysis of the phase 3 study showed that Voxzogo improved health-related quality of life among children with achondroplasia, particularly those associated with physical activities. After three years, the mean increase in Quality of Life in Short Stature Youth physical domain score was 6.0 as reported by caregivers and 6.3 as reported by children. These improvements were even more pronounced in children who grew more. For participants with ≥ 1 standard deviation increase in height z-score, the mean increase in physical domain score was 11.4 as reported by caregivers and 8.5 as reported by children.

“The clinical results at ACMG reinforce the long-term benefit we are seeing in children treated with Voxzogo, with a meaningful median height gain of more than 11 cm in children with achondroplasia following seven years of treatment,” said Hank Fuchs, president of worldwide research and development at BioMarin. “We are particularly encouraged by new data demonstrating the potential impact height gains from Voxzogo can have on quality of life, an outcome of incredible importance for children and families impacted by achondroplasia.”

Photo: Hank Fuchs, president of worldwide research and development at BioMarin