A year of daily subcutaneous vosoritide was associated with a 0.6-inch (1.5-cm) greater increase in height than placebo in children with achondroplasia, the most common form of human dwarfism.
There was no difference in the incidence of side effects in patients receiving the drug or placebo in this phase 3 study of the investigational drug from BioMarin Pharmaceuticals.
“To our knowledge, this study provides the first, robust evidence for an effective, precision therapy for achondroplasia that could fundamentally change the clinical management policies, growth trajectory, and treatment recommendations for children affected by this condition,” Ravi Savarirayan, MD, University of Melbourne, Australia, and colleagues report.
The study was recently published online in The Lancet.
“Over many years [this therapy] could lead to quite a significant increase in height [and] there were very few side effects that were attributable to the medication,” coauthor Joel Charrow, MD, Ann and Robert H. Lurie Children’s Hospital of Chicago, Illinois, summarized to Medscape Medical News.
And, he noted, it is also hoped “that it will affect other features of achondroplasia and prevent them, such as foramen magnum stenosis and shortening of the nasopharynx.”
“In theory, [infancy] would be the ideal time to start treatment to maximize the benefit,” he continued, and a trial of vosoritide that is enrolling infants with achondroplasia has just begun.
However, therapy for children with achondroplasia to make them taller is controversial, Charrow noted.
“In the dwarf community there are many people who are opposed to this kind of treatment because they don’t think that dwarfism should be medicalized or treated like a disease,” he said.
Asked to comment, David Ornitz, MD, PhD, who was not involved with the study, told Medscape Medical News that vosoritide appeared to be safe during 1 year of use, with no treatment-related adverse effects.
The efficacy results were “encouraging” for this “first potential pharmacological therapy to increase growth of achondroplasia patients.”
The drug could be “a pharmacological alternative to traditional surgical treatments or to not treating this genetic disease,” or it “could be used to augment the effectiveness of surgical therapies,” speculated Ornitz, of the Washington University School of Medicine, St Louis, Missouri.
Caveats include that daily injections might limit patient compliance and drug effectiveness, and it is not known whether efficacy would be sustained over the many years of treatment that would be required or if adverse effects would emerge later on, he noted.
Rare Genetic Mutation, Medical Complications in Addition to Short Stature
Achondroplasia is caused by a mutation in the fibroblast growth factor receptor 3 (FGFR3) gene that results in inhibited mineralization of chondrocytes (cartilage cells) in the growth plate (growing tissue near the ends of the long bones).
The mutation occurs in about one in 25,000 live births worldwide. And more than 80% of children with achondroplasia have parents of average height.
Achondroplasia results in a disproportionately short stature and disordered architecture in the long bones, spine, face, and base of the skull; affected children have an average-sized