FDA Approves Vosoritide for Achondroplasia in Children Under 5 Years

Credit: US Food and Drug Administration

The US Food and Drug Administration (FDA) has approved the supplemental New Drug Application (sNDA) for vosoritide (VOXZOGO®) to increase linear growth in pediatric patients ≤5 years of age with achondroplasia.¹

Announced by BioMarin Pharmaceutical Inc. on October 20, 2023, the expanded indication in the US now includes children of all ages with achondroplasia with open epiphyses – previously, vosoritide was indicated only for children ≥5 years of age.

The expanded approval was based on results from a randomized, double-blind, placebo-controlled, phase 2 clinical trial evaluating the efficacy and safety of vosoritide in children aged ≤5 years. Combined with evidence from the adequate and well-controlled phase 3 study in pediatric patients ≥5 years, the safety and effectiveness of vosoritide were established for the improvement of linear growth in children with achondroplasia with open epiphyses.

“[Vosoritide] is the only approved treatment for children with achondroplasia. Until now, it has only been approved in the US for children aged 5 and older with open growth plates,” said William Wilcox, MD, a professor of human genetics at Emory University, in a statement.¹ “I am delighted that [vosoritide] is now approved for younger children where we hope to have potentially greater impact by starting treatment earlier, and, as a result, a much longer treatment window.”

A rare disease, achondroplasia is the most common form of skeletal dysplasia leading to disproportionate short stature and is characterized by the slowing of endochondral ossification. The condition is caused by a change in the FGFR3 gene, a negative regulator of bone growth, and ≥80% of children with achondroplasia have parents of average stature. Global incidence rates of achondroplasia are about 1 in 25,000 live births, with approximately 800 children ≤5 years with achondroplasia in the United States.

Vosoritide has been tested in children with open epiphyses, accounting for approximately 25% of people with achondroplasia. Results from an open-label, long-term phase 2 extension study investigating vosoritide were presented at the 2023 European Society for Pediatric Endocrinology Meeting.²

Over a 4-year period, children aged ≥2 years who received vosoritide experienced a mean height Z-score improvement of 1.1 to 1.4 standard deviations (95% CI, 0.46 - 1.93) and a mean height gain of 6.3 to 7.8 centimeters (95% CI, 2.98 - 10.40 cm) when compared to untreated children with achondroplasia of the same age and sex.

The study findings also showed children ≤2 years treated with vosoritide for 3 years had a mean height Z-score improvement of 0.8 to 1.0 standard deviations (95% CI, 0.37 - 1.59) and a height gain between 3.5 and 3.9 cm (95% CI, 1.57 - 6.16 cm).

"We are pleased that [vosoritide] is now available for children of all ages with achondroplasia," said Hank Fuchs, MD, president of worldwide research and development, BioMarin, in a statement.¹ "We are grateful for the collaboration of the achondroplasia community, physicians, and the children and their families who have played a crucial role in advancing this clinical program. We also look forward to further understanding the potential role of [vosoritide] in other genetic short stature conditions, including hypochondroplasia."

Vosoritide has previously been approved in Europe for children with achondroplasia ≥2 years of age with open growth plates. In September 2023, the European Medicines Agency (EMA) Committee for Medical Products for Human Use provided a positive opinion recommending marketing authorization to expand the indication for vosoritide for injection to treat children with achondroplasia aged ≥4 months whose epiphyses are not closed. A final approval decision is expected from the EMA in late 2023.

References

1. U.S. Food and Drug Administration approves Biomarin’s VOXZOGO® (Vosoritide) for children under 5 years with achondroplasia. BioMarin Investors. October 20, 2023. Accessed October 20, 2023. https://investors.biomarin.com/2023-10-20-U-S-Food-and-Drug-Administration-Approves-BioMarins-VOXZOGO-R-vosoritide-for-Children-Under-5-Years-with-Achondroplasia.
2. BioMarin to present data showing long-term benefit of VOXZOGO® (Vosoritide) on growth in children with achondroplasia at 2023 European Society for Paediatric Endocrinology (ESPE) meeting. BioMarin Investors. September 21, 2023. Accessed October 20, 2023. https://investors.biomarin.com/2023-09-21-BioMarin-to-Present-Data-Showing-Long-Term-Benefit-of-VOXZOGO-R-vosoritide-on-Growth-in-Children-with-Achondroplasia-at-2023-European-Society-for-Paediatric-Endocrinology-ESPE-Meeting.