New Drug Increases Bone Growth in Children With Dwarfism

A four-year study from Johns Hopkins Medicine, the Murdoch Children’s Research Institute in Australia and seven other medical institutions has found that an experimental drug called vosoritide has increased the annual growth rate in children and teenagers with achondroplasia, a form of dwarfism. Vosoritide works by interfering with certain proteins that block bone growth.

For the study, Dr. Ravi Savarirayan and his colleagues enrolled a total of 35 children in four sequential cohorts. The first cohort of 8 children received vosoritide once-a-day, subcutaneous dose of 2.5 μg per kilogram of body weight. The second cohort of 8 children received 7.5 μg per kilogram of body weight. The third cohort of 10 children received 15.0 μg per kilogram and the final cohort of 9 children received 30.0 μg per kilogram.

“After 6 months, the dose in cohort 1 was increased to 7.5 μg per kilogram and then to 15.0 μg per kilogram, and in cohort 2, the dose was increased to 15.0 μg per kilogram; the patients in cohorts 3 and 4 continued to receive their initial doses.”

Results of the study (“C-Type Natriuretic Peptide Analogue Therapy in Children with Achondroplasia”) appear in the June 18, 2019 edition of The New England Journal of Medicine.

Ravi Savarirayan, M.B., BS, M.D., lead author/investigator of this research, told OTW, “The work stemmed from animal and human data that suggested this molecule could be a precision treatment for achondroplasia. The mouse model, when treated with vosoritide improved in terms of bone growth and spinal growth and this led to discussions (by me and others) with the drug company to trial this medication in children with achondroplasia.”

The team found that the patients' average height increased to about 6 centimeters (2.4 inches) per year is close to growth rates among children of average stature; the side effects of the drug were mostly mild, according to the researchers.

"An increase in the annual growth rate alone may have a positive effect on some patients' quality of life. For other patients, now and in the future, our hope is that the altered bone growth throughout the body could ease such problems as sleep apnea, neurological and leg and back problems, and improve their quality of life," said Julie Hoover-Fong, M.D., Ph.D., associate professor and director of the Greenberg Center for Skeletal Dysplasias at the Johns Hopkins McKusick-Nathans Institute of Genetic Medicine. "Right now, the results of the study show an impact on growth, and this effect is sustained, at least over nearly four years in this trial. The potential long-term benefit will take more time to observe."

"About half of these children will need spinal or other surgery, and this can mean a lot of time away from school as the child recovers and rehabilitates after surgery, which can affect important social connections," said Dr. Savarirayan, clinical geneticist and group leader of skeletal biology and disease at Murdoch Children's Research Institute.

Dr. Savarirayan told OTW, “The most important results were that the treatment appears safe with no major adverse events and resulted in sustained and significant increases in annual growth velocity over the 42-month study. I think the growth velocity changes, approximating growth of age matched children without achondroplasia was a noteworthy finding.”

“We are in a new era where disruptive therapies for skeletal dysplasia are well and truly here and maybe the need for orthopaedic and other surgeries in these children will be a thing of the past!”