By Annette Pinder

Teresa Quattrin, MD, UB Distinguished Professor of pediatrics, co-authored a global study suggesting a novel treatment for children with achondroplasia, a form of severe short stature. One of the most frequent bone disorders that prevents bone growth, especially in the arms and legs, achondroplasia causes very severe short stature. The average height for males is 52 inches and 49 inches for females. Individuals with achondroplasia can also experience other problems, including an unusually large head due to hydrocephalus (water in the brain), limited mobility of the elbows, spine curvature, sleep apnea, frequent ear infections, and back and leg pain.

About 80% of individuals with achondroplasia have a genetic mutation, with about 20% inheriting it from their mother or father. Worldwide, about 250,000 people are affected, with a frequency of about 4.6 cases in every 100,000 births, or 1 in every 22,000 births.

“The issue is the lack of conversion of cartilage into bone,” says Quattrin, senior associate dean for research integration at UB Jacobs School of Medicine and Biomedical Sciences, and a physician with UBMD Pediatrics. “This is due to a genetic mutation in the fibroblast growth factor receptor 3 (FGFR3).”

The randomized clinical study, funded and developed by Ascendis Pharma, included 57 participants ages 2 to 10 years who received either a subcutaneous injection with the new drug (TransCon CNP) or a placebo, was published Oct 2 in eClinical Medicine of The Lancet Discovery Science journal. Those who received the TransCon CNP injection experienced significantly improved growth and significantly improved annualized growth velocity compared to those who received the placebo, providing evidence that the new treatment significantly increased annualized growth velocity in children with achondroplasia with a favorable safety profile. TransCon CNP is an investigational prodrug of C-type natriuretic peptide (CNP), and its technology allows for continuous CNP exposure with once-weekly dosing.

According to Dr. Quattrin, the problem with the FGFR3 is that the receptor is overactive. The medicine used in this trial, CNP, counteracts the over-activation. She says, “CNP half-life is very short, but the medicine used in this trial took advantage of a new technology called TransCon that prolongs the half-life, allowing for weekly injections.” This is similar to what Ascendis has accomplished with growth hormone therapy, Quattrin says, noting Ascendis has received FDA approval for weekly growth hormone injections that were traditionally administered daily.

ACcomplisH is the first randomized, double-blind, placebo-controlled, dose-escalation of TransCon CNP in children with achondroplasia ages 2-10 years. It was well tolerated and resulted in a low frequency of injection site reactions with no incidence of symptomatic hypotension. Investigations are ongoing in an open-label extension period in which participants will be followed for two years, as well as in a pivotal trial, to further evaluate the balance of harms and benefits of the weekly dose of TransCon CNP.

UB was one of only eight U.S. centers chosen for the study, along with 11 other centers in Europe and Australia. The lead author of the study was Ravi Savarirayan, MD, of Murdoch Children’s Research Institute, Royal Children’s Hospital, University of Melbourne in Australia.