BioMarin Pharmaceutical Inc. announced that positive new data supporting the safety and efficacy of VOXZOGO® (vosoritide) in children with achondroplasia, as well as positive data for investigational uses in growth-related conditions, including idiopathic short stature (ISS) and Noonan syndrome, were presented at the 2024 Pediatric Endocrine Society (PES) Annual Meeting in Chicago, May 2-5, 2024. Researchers also presented results from additional studies highlighting the medicine's efficacy and impact on health-related quality of life (HRQoL) in children with achondroplasia. Positive results were presented from an investigator-sponsored Phase 2 study of VOXZOGO in children 3-11 years old with several genetic growth-related conditions, including Noonan syndrome and genetic mutations associated with ISS, such as aggrecan (ACAN) deficiency, heterozygous NPR2 mutations and neurofibromatosis 1 (NF1).

Results demonstrated marked improvement in annualized growth velocity (AGV) and height standard deviation (SD) across all the conditions studied. For the eight children who completed 12 months of treatment, mean AGV increased from a baseline of 3.7 cm/year to 8.5 cm/year and mean height SD changed from -3.6 SD to -2.9 SD. Of these eight children, three with NPR2 mutations had increases of 3.3, 4.8 and 9.3 cm/year; three with Noonan syndrome had increases of 3.0, 4.0 and 5.8 cm/year; and two with ACAN mutations had increases of 3.2 and 5.4 cm/year in their AGVs over baseline.

Safety results were consistent with the well-characterized safety profile of VOXZOGO. BioMarin has several clinical trials underway for growth-related conditions. A multinational observational study in children with hypochondroplasia (111-902) is currently recruiting participants, and the company plans to enter the treatment phase (Phase 3 trial) by mid-year.

Additionally, clinical studies in children with ISS (111-903 and 111-210) and multiple genetic short stature pathway conditions in the U.S. are anticipated to begin enrollment later this year. Data from a Phase 3 extension study of VOXZOGO in children with achondroplasia who began treatment at 10 years of age or older showed mean age- and sex-specific AGVs that were consistently higher compared to untreated children. These data examined 31 children who remained on treatment for more than three years, with a mean treatment exposure time of 3.57 years for girls and 3.87 years for boys.

The mean difference in AGV between treated and untreated children across ages 10-17 was 1.47 cm/year in girls and 1.71 cm/year in boys. AGV improvement in the VOXZOGO-treated group was maintained over a longer period of time compared to an average stature population, as opposed to an expected decline in AGV after the pubertal growth spurt. Safety was consistent with previous studies of VOXZOGO in younger children, and there was no evidence of a negative effect of treatment on bone age or pubertal development.

Additional data shared at PES, previously presented at the 2024 American College of Medical Genetics and Genomics Annual Clinical Genetics Meeting, demonstrated the positive effects of VOXZOGO on AGV in different age groups, as well as suggested positive impact on HRQoL. Results from a Phase 2 extension study showed that VOXZOGO maintained positive effects on linear growth over time in children who began treatment under age five. With more than seven 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.

Persistent growth-promoting effects of VOXZOGO were also demonstrated in a Phase 3 extension study in children aged 5-18 with achondroplasia with up to four years of treatment follow-up. Another Phase 3 study suggested that VOXZOGO improved HRQoL among children with achondroplasia, particularly aspects associated with physical functioning, an outcome of significant importance for children and families impacted by achondroplasia. After three years, the mean increase in Quality of Life in Short Stature Youth (QoLISSY) 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 those with = 1 SD 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).