First-of-its-kind trial boosts growth in children with rare disorders
The study demonstrates that CNP analogs have the potential to promote growth in children affected by these rare genetic disorders, opening doors to new treatment options.
In the first ever trial of vosoritide for short stature not caused by achondroplasia, researchers found an increase in growth for children with three rare genetic growth disorders where the RAS-MAPK pathway is affected – RASopathies, ACAN and NPR2 deficiency. Vosoritide, an analog of C-type natriuretic peptide (CNP), had previously been approved for treatment of children with achondroplasia.
The study, published in The Journal of Clinical Endocrinology & Metabolism, also reported that children with hypochondroplasia experienced increased growth, a finding previously presented by researchers at Children’s National Hospital.
The big picture
This phase 2 basket trial evaluated 30 participants between the ages of 3 and 11 years old with rare, genetic causes of short stature, all meeting a height requirement of less than -2.25 standard deviation score (SDS). The trial included a 6-month observation period followed by 12 months of vosoritide treatment. During the observation period, participants grew at an average rate of 4.53 cm per year. Once they began the therapy, their growth rate increased to an average of 8.09 cm per year – an increase of 3.56 cm per year.
The study demonstrates that CNP analogs have the potential to promote growth in children affected by these rare genetic disorders, opening doors to new treatment options. However, the authors emphasize the need for careful monitoring during long-term therapy, particularly for patients with aggrecan deficiency, due to the risk of developing conditions such as genu valgum and slipped capital femoral epiphyses.
The hold-up in the field
“Many patients do not get a comprehensive evaluation, including genetic testing, to identify the underlying cause of their short stature,” said Andrew Dauber, MD, MMSc, chief of Endocrinology at Children’s National and lead author of the trial. “In the last decade, our understanding of the genetics of growth disorders has made huge advances, and we can now identify new genetic subgroups of short stature.”
Dr. Dauber led an international team of experts in publishing new consensus guidelines on the genetic evaluation of short stature. Until recently, the only option for treatment has been growth hormone.
“Patients with NPR2 mutations had a particularly robust response to treatment, and so far, have not suffered any significant adverse events,” said Dr. Dauber. “Because NPR2 is the gene responsible for the CNP receptor, our treatment is precisely aimed at the pathway disrupted by these mutations.”
Leading the way
Children’s National is the only site in the world doing this type of work, leading in pediatric endocrinology for novel clinical trials in growth disorders.
Funded by an investigator-initiated grant from BioMarin, this trial is the first-of-its-kind to treat children with genetic short stature who do not have achondroplasia. Other growth-related conditions included in this phase 2 trial were Noonan syndrome, NPR2 mutations and Aggrecan mutations.
Additional authors from Children’s National include Anqing Zhang, PhD, Niusha Shafaie, MSc, Raheem Seaforth, BA, Kimberly Pitner, RN, Niti Dham, MD, MBA, Roopa Kanakatti Shankar, MBBS, MS.
Read the study, A Phase II Basket Trial of Vosoritide in Children with RASopathies, ACAN and NPR2 Deficiency, in The Journal of Clinical Endocrinology & Metabolism.
