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•After valoctocogene roxaparvovec treatment, total and encapsidated vector DNA are steadily cleared from the blood and shedding matrixes.•Risk of horizontal or germ line transmission following valoctocogene roxaparvovec is extremely low.

Achondroplasia is caused by pathogenic variants in the fibroblast growth factor receptor 3 gene that lead to impaired endochondral ossification. Vosoritide, an analog of C-type natriuretic peptide, stimulates endochondral bone growth and is in development for the treatment of achondroplasia. This phase 3 extension study was conducted to document the efficacy and safety of continuous, daily vosoritide treatment in children with achondroplasia, and the two-year results are reported.

There are no effective therapies for achondroplasia. An open-label study suggested that vosoritide administration might increase growth velocity in children with achondroplasia. This phase 3 trial was designed to further assess these preliminary findings.

Vosoritide is a drug developed for the treatment of achondroplasia and has demonstrated increases in the growth velocity of children with this condition. Achondroplasia is a skeletal dysplasia (a condition affecting children’s bones and joints meaning they do not grow in the typical way) and is also referred to as dwarfism. There are currently no approved treatments for achondroplasia, except for growth hormone in Japan. When a new drug is being developed, it is essential to conduct clinical studies after many other steps to assess how well the drug works and whether it has any side effects. These studies of new drugs are carried out before the drug is approved to treat, improve, or reduce physical problems of certain conditions. This summary reports the results from two clinical studies looking at vosoritide as a potential treatment for children with achondroplasia. Study A compared different doses of vosoritide to find out which is the safest and shows the best results with the fewest side effects. Study B looked at how well vosoritide works compared with a nonactive medicine (known as a placebo) and the side effects. In these studies, vosoritide increased bone growth velocity in children with achondroplasia. Children receiving the drug every day generally only had mild side effects. Serious health conplications were generally medical events seen in children with achondroplasia even if they do not take vosoritide. No children stopped taking vosoritide during the studies due to safety reasons. How well vosoritide works and the side effects in children over a longer period of time are still being studied. ClinicalTrials.gov NCT numbers: NCT02055157and NCT03197766.To read the full Plain Language Summary of this article, click on the View Article button above and download the PDF.Link to original articles hereand here.

Introduction:Long-term durable expression of hFVIII-SQ has been observed following BMN 270 (AAV5-hFVIII-SQ, valoctocogene roxaparvovec) single-dose administration in patients with severe hemophilia A. Although adeno-associated virus (AAV) vectors are replication incompetent and thus pose minimal risk for transmission or release into environment, a comprehensive assessment of vector shedding in secreta and excreta is required as part of the clinical development program. In addition, evaluation of vector biodistribution in blood is useful to characterize vector DNA processing and further understand the kinetics of vector DNA clearance. Vector shedding and biodistribution were evaluated from subjects from an ongoing Phase 1/2 study (Study 270-201, NCT02576795) and an ongoing Phase 3 study (Study 270-301, NCT03370913) following BMN 270 administration in patients with severe hemophilia A.