Vosoritide shows promise for children with certain genetic growth disorders

Andrew Dauber, M.D., M.M.Sc., endocrinologist at Children’s National Hospital, presented preliminary results from a phase II clinical trial of a new drug, vosoritide, used to treat children with certain growth disorders, at the Pediatric Endocrine Society annual meeting held virtually on May 1.

Vosoritide is a C-type natriuretic peptide analog that binds its receptor on chondrocytes, leading to increased chondrocyte proliferation and differentiation via its inhibition of the ERK1/2-MAPK pathway.

This is the first clinical trial in the world testing vosoritide in children with certain genetic causes of short stature, including hypochondroplasia, Noonan syndrome, NPR2 mutations and Aggrecan mutations.

To date, 34 participants have enrolled in the trial with a median baseline height of -3.2 SD (interquartile range (IQR) -3.7, -2.6). 18 subjects have initiated on vosoritide and twelve have completed six months of therapy. The authors note that the mean increase in annualized growth velocity (AGV) was 1.8 cm/yr for subjects with hypochondroplasia and 6.1 cm/yr for subjects with Noonan syndrome or NPR2 mutations. The two subjects with NPR2 mutations had increased AGVs of 4.4 and 9.2 cm/yr, while the two subjects with Noonan syndrome had increased in AGVs of 7.5 and 3.3 cm/yr. One of the Noonan syndrome subjects was previously treated with growth hormone (GH) for 2 years and AGV was 6.7 cm/yr while on GH, 4.1 cm/yr during the trial 6-month observation period and 11.6 cm/year during the first six months of vosoritide treatment.

To the researchers, the safety profile is quite reassuring. So far, the preliminary results showed increased growth in all the genetic subgroups with the patients with hypochondroplasia demonstrating a response similar to that seen previously in patients with achondroplasia. While the results are very promising for patients with Noonan syndrome and NPR2 mutations, the clinical trial must be completed before drawing further conclusions. The experts also plan to submit the study to a peer-reviewed journal in the future to validate the findings.

The big picture

This is the first medication that directly targets the pathway in chondrocytes (cells in the growth plate that make the bones grow longer) affected by these specific mutations. This means that the novel approach may give patients additional therapeutic options outside of growth hormone.

Why we’re excited

“These are the first patients in the world to ever receive this medication for their conditions,” said Dr. Dauber. “The results are very promising and may change the way we practice medicine. Patients have come from all over the world to participate in the study.”

Children’s National leads the way

This clinical trial funded by BioMarin is the first of its kind to treat children with genetic short stature who do not have achondroplasia. Children’s National is the only site in the world offering this therapy for patients with these conditions.

Find out more about the trial here.