First Patient Dosed in Phase 2 Study of Vosoritide For Infants with Achondroplasia

The first participant was dosed in BioMarin Pharmaceutical Inc.’s global phase 2 study for vosoritide, an analog of C-type Natriuretic Peptide (CNP), in infants and young children with achondroplasia.

Achondroplasia is a skeletal dysplasia and is characterized by the failure of normal conversion of cartilage into bone, resulting in disproportionate short stature. Achondroplasia is the most common form of disproportionate short stature in humans.

Vosoritide, also known as BMN 111, is an investigational drug derived from a natural human peptide, which is a positive regulator of bone growth. By binding to a specific receptor, vosoritide initiates intracellular signals that discourage the overactive FGFR3 pathway, counteracting the effects caused by the FGFR3 mutation. Since children under the age of 18 with achondroplasia have bones still amenable to growth, vosoritide is being assessed in them.

"Vosoritide represents an innovative therapy to treat the underlying cause of achondroplasia. At the molecular level, vosoritide corrects the signaling process that determines skeletal growth and proportionality of bones, while the body is still growing," Hank Fuchs, MD, president, Worldwide Research and Development at BioMarin, said in a recent statement.

Seventy infants and young children with achondroplasia aged 0 to less than 60 months are being assessed in the randomized, placebo-controlled phase 2 study of vosoritide for the duration of 52 weeks. A subsequent open-label extension will follow the study. Additionally, in order to determine their respective baseline growth prior to entering the phase 2 study, participating children have completed a minimum 3-month baseline study.

Evaluation of the safety, tolerability, and effect of vosoritide on height Z-scores—which is the number of standard deviations in relation to the mean height of age-matched, average stature children—have been defined as the study’s primary endpoints.

In addition, BioMArin is planning augmentation of the height Z-score data with assessments that include proportionality, functionality, quality of life, sleep apnea, and foramen magnum dimension, as well as the advent of major illnesses and surgeries.

Primary measures in the phase 2 study will include the incidence of treatment-emergent adverse events according to safety and tolerability every 3 months through to study completion, which is expected to be in October 2022. This measure will include the number of study participants with treatment-emergent adverse events and treatment-emergent serious adverse events.

Secondary measures will include growth velocity, growth parameters, and body proportions in the scope of efficacy in the time frame of up to 5 years near final adult height of the patient.

"We are pleased to have initiated this study in the youngest people with achondroplasia,” added Dr Fuchs, “we and are grateful to the children and their families who have been participating in our ongoing studies and those who are now participating in this phase 2 study.”

Previously, vosoritide was granted orphan drug designation in both the United States and Europe.