Endocrine Abstracts

JOINT1216

Achondroplasia (ACH) is a common form of disproportionate short stature caused by impaired endochondral bone growth. Vosoritide, a recombinant C-type natriuretic peptide, stimulates endochondral bone growth and is approved in 42 countries for children with ACH until the closure of epiphyses. Here, we demonstrate the effect of long-term vosoritide treatment on sustained annualized growth velocity (AGV) and estimate height gain compared to untreated children with ACH if vosoritide treatment was continuous from age 6 months until final adult height (FAH). Pooled mean AGV (cm/year) by integer age and sex while on treatment is reported from the phase 3 study 111-301 (NCT03197766) and its ongoing long-term extension (LTE) 111-302 (NCT03424018) and the phase 2 study 111-206 (NCT03583697) and its ongoing LTE 111-208 (NCT03989947). Study 111-301 evaluated 15 µg/ kg/day vosoritide in children with ACH aged ≥5 to <18 years at screening until FAH, and 111-206 evaluated 30 and 15 µg/ kg/day vosoritide in children with ACH from 4 months to <5 years until near-FAH. Untreated data from CLARITY served as an external ACH control population. Interval AGV for 6±1 and 12±3 months were derived from paired height assessments from age 4 months to 3 years and age 3 years to FAH, respectively. The midpoint of the 2 height assessments determined the associated age to summarize AGV. Total height gain was derived by subtracting the difference in AGV between the treated and untreated population per age. Confidence intervals (CIs) were estimated by bootstrap methods. By the data cutoff (February 25, 2024), mean treatment follow-up in 192 total participants was 4.7 (range, 1.8-7.1) years for those from 111-302 (n=119) and 3.8 (range, 1.1-5.7) years for those from 111-208 (n=73). Both studies provided mean AGV (95% CI) estimates at ages 5-9 years; CIs overlapped with no trend whether treatment started before or after age 5 years. Given these analyses, expected estimated height gain for children with ACH if continuously treated from 6 months to FAH was 21.7 cm (95% Cl, 18.7-24.6) in females and 26.4 cm (95% Cl, 22.9-29.8) in males compared to untreated children. In these results from the longest follow-up of a phase 3 study of children with ACH, vosoritide treatment sustained increases in AGV. For the first time, we predict total height gain for children with ACH if they were to be treated continuously with vosoritide from age 6 months to FAH compared to untreated children.