SAT-213 Trial of Vosoritide for Treatment of Short Stature in Turner syndrome: Preliminary Data

Abstract Disclosure: R. Kanakatti Shankar: RKS has received research funding from BioMarin Pharmaceutical Inc., is a consultant for BioMarin, with fees paid to her institution.. N. Shafaei: None. A. Zhang: None. K. Pitner: None. N. Dham: None. A.N. Dauber: AD has received grant funding from BioMarin Pharmaceutical Inc., and is a consultant for BioMarin with fees paid to institution. Turner syndrome (TS) is a genetic condition associated with the absence of whole or part of the second sex chromosome in a phenotypic female. Haploinsufficiency of the SHOX gene on the pseudo autologous region of the sex chromosome is one of the mechanisms of short stature commonly seen in TS and is linked to increased FGFR3 signaling as well as direct effects on the C-type natriuretic peptide (CNP). Vosoritide is a modified recombinant CNP analog that is approved for treatment of short stature in achondroplasia and enhances endochondral bone growth by inhibiting the ERK1/2-MAPK pathway and FGFR3 signaling. Hence, we hypothesized that vosoritide may increase height gain in TS by promoting chondrocyte differentiation and growth. Pre-pubertal girls (ages 3-11 years) with karyotype-confirmed TS <- 2 SD for height are eligible for recruitment to a single center Phase II open label clinical trial of vosoritide if either naïve to growth hormone (GH) or with annualized growth velocity (AGV) of <50%ile for age and sex despite treatment with GH for more than a year. Subjects are excluded if they have chronic medical conditions affecting growth (e.g. untreated celiac disease, inflammatory bowel disease etc.), or hemodynamically severe congenital or acquired cardiovascular disease which places the subject at increased risk of an adverse cardiac outcome in the setting of hypotension. GH is discontinued prior to the screening visit and participants receive daily subcutaneous injections of vosoritide using the weight-based dosing band strategy (approved for achondroplasia). Dose is adjusted for weight at 6 months and followed for a total of 12 months on the trial. The primary outcomes are change in AGV and height SD from baseline (efficacy) and incidence of adverse events (AEs) (safety). We report on preliminary results of the ongoing trial: 4 subjects are enrolled, one failed screen and was excluded from participation; 3 have completed 6 months of treatment. One participant (age 6y) is GH naïve and increased AGV from 4.46cm/year at baseline to 10.5 cm/year at the 6 month visit on vosoritide (+6cm/y), with a height SD increase of +0.5 SD. Participants with prior GH exposure (ages 9 and 10y) increased AGV by +4.9 and +1.57 cm/y at 6 months with vosoritide, over the baseline AGV on GH treatment. Height SD increased by +0.38 and +0.22 respectively for these 2 participants. Vosoritide was well tolerated, with transient injection site erythema/swelling (Grade 1-2) and no subjects discontinued participation due to AEs. There were no episodes of hypotension or serious AEs related to treatment. Data from the 12-month visit are anticipated. Preliminary data are encouraging for safety and efficacy of vosoritide injections in both GH naïve and in previously GH-treated girls with TS to improve height gain in the short term. Longer term data and ongoing enrollment are anticipated to clarify the potential role of vosoritide in TS. Presentation: Saturday, July 12, 2025