IMPE Abstracts

Objectives: Vosoritide is a potent stimulator of endochondral bone growth and is in development for the treatment of achondroplasia, the most common form of disproportionate short stature. We previously reported on a 52-week, phase 3, pivotal study that demonstrated a significant improvement in annualized growth velocity (AGV) when vosoritide was compared to placebo in children with achondroplasia aged 5-18 years (Savarirayan et al, Lancet, 2020). Thi...

Background: FGFR3 is a negative regulator of bone growth. Gain-of-function mutations in the FGFR3 gene result in different skeletal osteochondrodysplasias, including achondroplasia (ACH) and hypochondroplasia (HCH). ACH is the most common form of rhizomelic short stature, affecting between 1 in 15,000 and 1 in 30,000 live births worldwide. The incidence of HCH is thought to be approximately the same as ACH. Currently, there is only one approved therap...

Introduction: The genetic factors are frequently implicated in the growth impairment of short stature (SS) children, whether they are syndromic or apparently healthy. However, the investigation recommended by the consensus fails to establish the etiology in most cases. The difficulty to search for candidate genes increases the importance of using a hypothesis-free approach as whole exome sequencing (WES) for these children. Objective: To determine the diagnost...

Background: Somatrogon is a once-weekly treatment for children with pediatric GH deficiency (pGHD). The goal of this study was to simulate IGF-1 and IGF-1 SDS profiles and calculate the ratio and differences of observations to 96-hour values over the dosing interval.Methods: A population PK model was developed using data from a Phase 2 study and a Phase 3 study in children with pGHD. An indirect-response PK/PD model link...