The Lancet publishes detailed vosoritide phase III data demonstrating statistically significant increase in annualized growth velocity (AGV) over 52 weeks in children with achondroplasia.- BioMarin

BioMarin Pharmaceutical Inc. announced that The Lancet has published online results from a randomized, double-blind, phase III, placebo-controlled, multicenter trial for vosoritide , an investigational analog of C-type Natriuretic Peptide (CNP), in children aged 5 to 18 years with achondroplasia. Achondroplasia is the most common form of disproportionate short stature in humans. The data demonstrated that daily subcutaneous administration of vosoritide to children with achondroplasia resulted in significantly increased growth velocity and height Z scores over baseline after one year of treatment as compared to those who received placebo with similar adverse effect profiles. The primary endpoint was change from baseline in AGV at 52 weeks in participants administered daily subcutaneous injections of vosoritide, at a dose of 15.0 µg/kg/day, compared with placebo. The findings demonstrated that the adjusted mean difference in AGV between children in the vosoritide group and placebo group was 1.57cm per year in favor of vosoritide (95% CI: 1.22 - 1.93, p value <0·0001), a substantial proportion of the approximately 2 cm yr agv deficit relative to average-stature children. the results of subgroup analyses for change from baseline in agv were consistent with the overall mean difference between treatment groups in favor of vosoritide, with all 95% cis overlapping. baseline agv was calculated from the increase in standing height measured over the last six months of the run-in study. post-baseline agv was calculated from standing height at baseline and 52-weeks, and then summarized by treatment arm. as of october 30th, 2019, the 52-week placebo-controlled study was completed, and 119 participants had enrolled in the extension study, where all children are receiving vosoritide.> Secondary Endpoints, Height Z Score : A prespecified analysis of the secondary endpoint of change from baseline in height Z score, (which measures the height deficit in standard deviations relative to the mean forage- and gender-matched average stature children), was also performed. The findings demonstrated that the adjusted mean difference in height Z score change from baseline between children in the vosoritide group and placebo group was +0.28 in favor of vosoritide (95% CI: 0.17 – 0.39, p value <0.0001). the results of subgroup analyses were consistent and showed that all estimates of the mean difference between treatment groups were greater than or equal to zero and the 95% cis were overlapping. there were no adverse effects on, or significant improvements in upper to lower body segment proportionality in children receiving vosoritide during this 52-week study . as expected due to the duration of follow up, no statistically significant changes in secondary endpoints related to wider health outcomes such as quality of life, activities of daily living, and frequency and type of medical and surgical interventions were found. either a longer treatment period or earlier treatment initiation will be required to detect these changes. as such, an ongoing, open-label, phase iii, extension study will continue to evaluate the balance of benefits and harms of vosoritide until the children reported in this study reach final adult height. this study will collect data regarding vosoritide therapy on wider health measures compared with registry data of untreated children with achondroplasia. this long-term study will also provide data on whether treatment of children with achondroplasia with vosoritide will result in a pubertal growth spurt, which appears to be absent in this condition, and provide the opportunity to detect any harms associated with long-term therapy. in addition, a phase ii, randomized, double-blind, placebo-controlled trial of vosoritide in infants and younger children (aged 3 months to less than 60 months) with achondroplasia has been designed to provide further insights into the long-term treatment effects on body proportionality and growth, as well as how earlier treatment might affect the most substantial medical complications (e.g., foramen magnum stenosis with brainstem compression). safety summary :vosoritide, administered at 15.0 ug kg day in this phase iii randomized, double-blinded placebo-controlled study over one year, was generally well tolerated. the majority of adverse events (aes) were mild and no serious adverse events were reported as study drug-related. injection site reactions were the most common drug-related aes, and all were transient. no clinically significant blood pressure decreases, or new safety findings were observed. see-published:september 05-,"once-daily, subcutaneous vosoritide therapy in children with achondroplasia: a randomised, double-blind, phase 3, placebo-controlled, multicentre trial."-prof ravi savarirayan, md ,louise tofts, mbbs, et.al. 2020doi:https: doi.org 10.1016 s0140-6736(20)31541-5.>