Achondroplasia is a genetic condition that slows the conversion of cartilage to bone in the growth plate (epiphysis). The Food and Drug Administration (FDA) has granted accelerated approval to vosoritide (Voxzogo) to treat children ages five years and older with achondroplasia who still have open epiphyses. Continuation of approval for this indication will be based on clinical trial data that confirms clinical benefit. Vosoritide is given daily as a subcutaneous injection.

According to the National Organization for Rare Disorders, achondroplasia occurs in approximately one in 20,000 to 30,000 live births. Adults with achondroplasia have a height of between 42 and 56 in. Although achondroplasia is a genetic condition, most children with achondroplasia are born to parents of normal height. According to Johns Hopkins Medicine, the most common symptoms are shortened arms and legs; large head (macrocephaly) with a prominent forehead and a flattened nasal bridge; crowded or misaligned teeth; curved lower spine; poor muscle tone and loose joints; and delayed developmental milestones. (For more, see http://www.hopkinsmedicine.org/health/conditions-and-diseases/achondroplasia.)

Bone growth occurs when cartilage cells, known as chondrocytes, form new bone. The rate of growth is controlled by stimulation of chondrocyte receptors that inhibit or encourage bone growth. When stimulated, fibroblast growth factor receptor 3 (FGFR3) inhibits bone growth and natriuretic peptide receptor B causes bones to grow. Vosoritide binds to natriuretic peptide receptor B, preventing the action of FGFR3 downstream. Consequently, vosoritide promotes chondrocyte proliferation and differentiation.

The safety and effectiveness of vosoritide was determined in a multicenter, randomized, double-blind, placebo-controlled, phase 3 study. A total of 121 subjects with genetically confirmed achondroplasia were randomized to subcutaneous vosoritide or placebo daily for 52 weeks. The primary end point was change from baseline in annualized growth velocity (AGV)-or rate of height growth-at week 52 compared with placebo. The study found that subjects who received vosoritide grew an average 1.57 cm taller than those who received placebo. After the phase 3 study, there was an open-label extension study. After two years of follow-up, the improvement in AGV was maintained and was the basis for vosoritide's accelerated approval.

The most common adverse effects of treatment are injection site erythema, swelling, and urticaria; vomiting; arthralgia; decreased blood pressure; and gastroenteritis. Vosoritide's labeling carries a warning that the drug can cause transient hypotensive episodes.

Nurses should confirm that the child has had a meal and 240 to 300 mL of fluid in the hour prior to administration of vosoritide to prevent or minimize hypotensive episodes. The child's weight should be confirmed, as both the drug dose and the concentration of reconstituted drug are weight dependent. As vosoritide comes in single-dose vials with different concentrations (0.4 mg, 0.56 mg, or 1.2 mg), the product label needs to be checked to confirm it matches the order. Nurses should instruct parents or caregivers to feed and hydrate the child before a dose; to reconstitute the drug using the prefilled syringe of sterile water provided as the diluent; to administer a subcutaneous injection; and to rotate injection sites. If the child exhibits symptoms of low blood pressure, such as dizziness, feeling tired, or nausea, the child should lie down and be given fluids. Nurses and NPs should assess for body weight, growth, and physical development every three to six months while the child receives vosoritide. Vosoritide must be permanently discontinued once there is closure of the epiphyses.

For complete prescribing information for vosoritide, see http://www.accessdata.fda.gov/drugsatfda_docs/label/2021/214938s000lbl.pdf.