THU173 Subanalysis By Tanner Stage In Phase 3 Trials In Children And Adolescents With Growth Hormone Deficiency Treated With Lonapegsomatropin
Authors: Hofman Paul , Thornton Paul S , Nadgir Ulhas M , Saenger Paul , Chertok Elena , Aghajanova Elena M , Mao Meng , Zhao Carol , Ochoa-Maya Margarita R , Komirenko Allison , Shu Aimee D , Maniatis Aristides K 
Published: October 2023

Disclosure: P. Hofman: Speaker; Self; Novo Nordisk, Eli Lilly & Company. P.S. Thornton: Research Investigator; Self; Ascendis, Pfizer, Inc., Opko, Zealand, Rezolute, Spruce. Other; Self; Johnson &Johnson, Rezolute. U.M. Nadgir: None. P. Saenger: None. E. Chertok: None. E.M. Aghajanova: Speaker; Self; Berlin Hemi Menarini. M. Mao: Employee; Self; Ascendis Pharma. C. Zhao: Employee; Self; Ascendis Pharma. M.R. Ochoa-Maya: Employee; Self; Ascendis Pharma. A. Komirenko: Employee; Self; Ascendis Pharma. A.D. Shu: Employee; Self; Ascendis Pharma. A.K. Maniatis: Advisory Board Member; Self; Novo Nordisk, Ascendis Pharma, Pfizer, Inc. Consulting Fee; Self; Novo Nordisk, Ascendis Pharma. Research Investigator; Self; Novo Nordisk, Pfizer, Inc., OPKO, Ascendis Pharma. Speaker; Self; Novo Nordisk, Ascendis Pharma.

Background: Historically, the treatment paradigm in pediatric growth hormone deficiency (GHD) has been to consider increased doses (up to 0.7 mg hGH/kg/week) later in pubertal development to maximize growth outcomes, although this is not a routine recommendation (Mauras et al. JCEM. 2000;85(10):3653-3660, Grimberg et al. Horm Res Paeds. 2016;86(6):361-397). The enliGHten open-label extension trial of once-weekly lonapegsomatropin provided the opportunity to evaluate dosing, efficacy, and safety outcomes in a group of children that includes more advanced Tanner Stages. Lonapegsomatropin (TransCon hGH), a once-weekly prodrug of somatropin approved for the treatment of pediatric GHD by the FDA and EMA, uses TransCon technology to transiently link a parent drug to an inert carrier. In the pivotal phase 3 heiGHt trial, lonapegsomatropin demonstrated noninferior and superior annualized height velocity and a comparable safety profile to daily somatropin in children with GHD. The current analysis explores IGF-1 levels, dose adjustments, and height outcomes by Tanner Stage. Methods: Three phase 3 trials assessed safety and efficacy of lonapegsomatropin: heiGHt (treatment-naïve trial), fliGHt (switch trial), and enliGHten (open-label extension trial). Participants treated in the 3 phase 3 trials were included in this analysis (data snapshot date, September 1, 2021). Data were analyzed by the most recent Tanner Stage at time of assessment in 3 groups: Stage 1 and 2; Stage 3; and Stage 4 and 5. Association between Tanner Stage and IGF-1 SDS measurements, lonapegsomatropin dose, and height SDS were examined using mixed repeated models with Tanner stage as time-varying covariate. Relationship between dose reduction and change in IGF-1 SDS was summarized by Tanner stage. Results: With a mean follow-up of 157 weeks (N=306) on lonapegsomatropin treatment, the analysis showed that later Tanner Stages (3, 4-5) were correlated with higher average IGF-1 SDS (versus Stages 1-2). There was a small difference in lonapegsomatropin dose across Tanner Stage groups, with participants in Stages 4-5 receiving the lowest mean dose (0.19 mg hGH/kg/wk) compared with Stages 1-2 (0.23 mg hGH/kg/wk) or Stage 3 (0.22 mg hGH/kg/wk). Among patients with dose reduction, a decrease of lonapegsomatropin of 0.02 mg hGH/kg corresponded to a consistent drop in average IGF-1 SDS across all Tanner Stages (overall, 0.16 SDS; Stages 1-2, 0.21 SDS; Stage 3, 0.16 SDS; Stages 4-5, 0.21 SDS). Participants across all subgroups experienced continued growth as expected over time. Conclusions: This analysis showed that it was possible to maintain consistent height SDS improvements in children and adolescents in Tanner Stages 3-5 without an increase in the mean lonapegsomatropin dose. Lonapegsomatropin dose reductions resulted in predictable linear IGF-1 decreases across Tanner Stages.

Presentation: Thursday, June 15, 2023