BioMarin Pharmaceutical Inc. announced that the New England Journal of Medicine (NEJM) published online today results from a Phase 2 dose-finding and extension study for vosoritide, an investigational analog of C-type Natriuretic Peptide (CNP), in children with achondroplasia. The data demonstrated that vosoritide was generally well tolerated with a mild side effect profile and resulted in a sustained increase in annualized growth velocity for up to 42 months in children aged 5 to14 years with achondroplasia, the most common form of disproportionate short stature in humans. The results will also appear in the July 4th printed issue.
In addition, the company announced that it had met its enrollment goal of the first cohort (n=30) of a separate Phase 2 study of vosoritide in infants and young children ages two to five years.
"Our research continues to investigate the potential of vosoritide to assist in skeletal growth in children with achondroplasia," said Ravi Savarirayan, M.B., B.S., M.D., lead author of the NEJM study and investigator from the Murdoch Children's Research Institute, Royal Children's Hospital, University of Melbourne, Parkville, Victoria, Australia. "I am hopeful that this ongoing clinical development program will be able to demonstrate a meaningful difference for children with achondroplasia."
The NEJM publication described results of an ongoing open-label, Phase 2 study in children with achondroplasia, where vosoritide demonstrated a sustained increase in height and associated height Z scores for up to 42 months of treatment in children in cohort 3 receiving a continuous dose of 15 µg/kg/day. Annualized growth velocity increased from baseline in all cohorts during each 12-month interval by 1.10 to 2.34 cm/year through 42 months. In cohort 3 (n=10) receiving 15 μg/kg continuous dosing from baseline, the mean annualized growth velocity derived between 30 and 42 months was 5.51 cm/year representing a 1.46 cm/year (95% CI −0.15, 3.07) change from baseline. In cohort 4 (n=9) receiving 30 μg/kg continuous dosing from baseline, the mean annualized growth velocity between 18 and 30 months was 5.60 cm/year representing a 1.10 cm/year (95% CI −0.27, 2.48) change from baseline.
"The results published today by NEJM demonstrate the importance of researching a therapeutic option that explicitly addresses the underlying cause of achondroplasia," said Hank Fuchs, M.D., President, Worldwide Research and Development at BioMarin. "The rapid completion of enrollment in the two to five year old cohort of our ongoing infant and toddler Phase 2 study is an important milestone for our clinical program. We are grateful to the children and their families for their participation in our ongoing clinical trials as we continue to investigate important and sustained outcomes for those with achondroplasia, as well as contribute to the body of scientific literature on achondroplasia."
Once-daily subcutaneous administration of vosoritide was associated with a side-effect profile that was generally mild. Injection-site reactions were mild and transient. Blood pressure and pulse rate were monitored frequently after the initial dose was administered. All reductions in blood pressure from test to test were reported as non-serious and transient and resolved without medical intervention; none resulted in interruption or discontinuation of the study-drug regimen. Serious adverse events occurred in four children and included grade 3 obstructive sleep apnea, grade 1 tonsillar hypertrophy, grade 3 thyroglossal cyst, and grade 3 syrinx. No deaths occurred. No adverse events related to disproportionate skeletal growth or clinically significant adverse cardiovascular effects were observed. In addition, there were no reports of grade 3 or higher or serious hypersensitivity reactions.
Height Z-scores also continued to improve over 42 months and there was proportional growth between the upper and lower body segments. Standing height was converted to an age and sex appropriate Z-score by comparison with Centers for Disease Control and Prevention reference standards for average-height children. Dose-dependent increases in height Z-scores were observed in the children who received a dose of up to 15.0 µg/kg/day for 6 months; those who received a dose of 30.0 µg/kg/day had a similar increase. Vosoriti...
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