Rare Daily Staff

The U.S. Food and Drug Administration approved BioMarin Pharmaceutical’s Voxzogo, a once-daily injection to improve growth in children five years of age and older with achondroplasia and open epiphyses (growth plates), meaning these children still have the potential to grow.

“Today’s approval fulfills an unmet medical need for more than 10,000 children in the United States and underscores the FDA’s commitment to help make new therapies available for rare diseases,” said Theresa Kehoe, director of the Division of General Endocrinology in the FDA’s Center for Drug Evaluation and Research. “With this action, children with short stature due to achondroplasia have a treatment option that targets the underlying cause of their short stature.”

Achondroplasia is the most common cause of dwarfism. It is characterized by slowing of endochondral ossification, which results in disproportionate short stature and disordered architecture in the long bones, spine, face and base of the skull. This condition is caused by a change in the fibroblast growth factor receptor 3 gene (FGFR3), a negative regulator of bone growth. Beyond disproportionate short stature, people with achondroplasia can experience serious health complications, including foramen magnum compression, sleep apnea, bowed legs, mid-face hypoplasia, permanent sway of the lower back, spinal stenosis, and recurrent ear infections. Some of these complications can result in the need for invasive surgeries such as spinal cord decompression and straightening of bowed legs. In addition, studies show increased mortality at every age.

More than 80 percent of children with achondroplasia have parents of average stature and have the condition as the result of a spontaneous gene mutation. The worldwide incidence rate of achondroplasia is about one in 25,000 live births.

Voxzogo, a modified C-type natriuretic peptide (CNP), directly targets the underlying pathophysiology of achondroplasia by down regulating fibroblast growth factor receptor 3 (FGFR3) signaling and consequently promoting endochondral bone formation.

Voxzogo’s safety and efficacy in improving growth were evaluated in a year-long, double-blind, placebo-controlled, phase 3 study in participants five years and older with achondroplasia who have open epiphyses. In the study, 121 participants were randomly assigned to receive either Voxzogo injections under the skin or a placebo. Researchers measured the participants’ annualized growth velocity, or rate of height growth, at the end of the year. Participants who received Voxzogo grew an average 1.57 centimeters taller compared to those who received a placebo.

The most common side effects of Voxzogo include injection site reactions, vomiting and decreased blood pressure. Voxzogo’s labeling also lists decreased blood pressure as a warning and precaution, which means it is a potentially serious side effect.

The FDA approved Voxzogo under the accelerated approval pathway, which allows for earlier approval of drugs that treat serious conditions and fill an unmet medical need, based on a surrogate or intermediate clinical endpoint. A condition of this accelerated approval is a post-marketing study that will assess final adult height. This application also received priority review designation.

Voxzogo was previously approved by the European Commission at the end of August 2021.

Photo: Theresa Kehoe, director of the Division of General Endocrinology in the FDA’s Center for Drug Evaluation and Research

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