Rare Daily Staff

BioMarin Pharmaceutical reported positive final results from its phase 3 study evaluating the efficacy and safety of vosoritide, its experimental treatment for children with achondroplasia, the most common form of disproportionate short stature.

Achondroplasia is characterized by failure of normal conversion of cartilage into bone. Besides disproportionate short stature, people with achondroplasia can experience serious health complications, including foramen magnum compression, sleep apnea, bowed legs, mid-face hypoplasia, permanent sway of the lower back, spinal stenosis and recurrent ear infections. Some of these complications can result in invasive surgeries, such as spinal cord decompression and straightening of bowed legs. In addition, studies show increased mortality at every age.

Vosoritide, an experimental analog of C-type Natriuretic Peptide (CNP), was tested in children whose growth plates are still open, typically those less than 18 years of age. This is approximately 25 percent of people with achondroplasia. There are currently no licensed medicines for achondroplasia in the United States, Europe, Latin America, and the Middle East. Vosoritide has been granted orphan drug designation in both the United States and Europe.

In the study, the placebo-adjusted change from baseline in growth velocity after one year of treatment with vosoritide, the primary endpoint, was 1.6 cm/year. The study enrolled 121 children aged 5 to 14 with achondroplasia. Vosoritide was generally well tolerated with no clinically significant blood pressure decreases.  Based on these results, BioMarin plans to meet with health authorities in the first half of 2020 to discuss plans for submitting marketing applications.

“The placebo-controlled study demonstrated a strong increase in growth velocity across the broad population studied,” said Hank Fuchs, president of Worldwide Research and Development at BioMarin. “These results when combined with the long-term benefits seen in the phase 2 study provide hope for a significant and sustained benefit for children with achondroplasia.”

The global phase 3 study is a randomized, double-blind, placebo-controlled study of vosoritide in 121 children with achondroplasia aged 5 to 14 for 52 weeks whose growth plates are still open. Children in this study have completed a minimum six-month baseline study to determine their respective baseline growth velocity prior to entering the phase 3 study.  The primary endpoint of the study is the change in growth velocity from baseline over one year in children treated with vosoritide compared to placebo.

A wide range of secondary and exploratory endpoints include anthropometric measures such as height Z-score, body and limb proportionality and joint geometry; biochemical, biomarker and radiological assessments of bone growth and health; and evaluations of health-related quality of life, developmental status, and functional independence. These additional endpoints address the overall impact vosoritide has on achondroplasia and will continue to be evaluated in an ongoing open-label extension study where all subjects receive active treatment.

“As a treating physician, it is exciting to see these compelling results of an investigational therapy confirming its potential to be the first medical therapy to treat the underlying cause of achondroplasia,” said John Phillips, professor of pediatrics at Vanderbilt University Medical Center.  “Importantly, this data adds to an increasing body of scientific data on a potential breakthrough in the treatment for achondroplasia.”

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

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