Endocrine Abstracts

In patients with adult growth hormone deficiency (AGHD), the dose of growth hormone (GH) replacement is individualised based on clinical outcome, insulin-like growth factor-I (IGF-I) levels and adverse reactions. The aim of this analysis was to characterise dose–IGFI–response for somapacitan, a long-acting reversible albumin-binding GH derivative, and to derive expected IGF-I levels for various starting doses. Somapacitan dose–IGF-I–response analysis was conducted in 330 patients with AGHD across three phase 3 trials; GH treatment-naïve patients (NCT02229851), and patients previously treated with GH (NCT02382939, NCT03075644) were analysed using a population pharmacokinetic/pharmacodynamic (PK/PD) model. Dose titration was performed with starting doses of 1.5 mg/week, 1.0 mg/week, and 2.0 mg/week, respectively, for patients ≤ 60 years old, > 60 years old, and female patients taking oral oestrogen. The impact of demographic covariates (weight, sex, oral oestrogen, age and race [White/other, Asian Japanese, Asian non-Japanese]) upon PK/PD parameters was investigated. Individual PK/PD parameter estimates were used to derive average IGF-I standard deviation score (SDS) at the fixed dose level after titration, and for each individual across the 0.1–8.0 mg/week dose range. Age, sex and oral oestrogen use were the most influential covariates on somapacitan dose–IGF-I–response. Higher doses of somapacitan were required to reach similar IGF-I targets in female patients, particularly those taking oral oestrogen, compared with male patients. Lower doses were required to reach similar IGF-I targets in > 60 vs ≤ 60 year old patients. Race and body weight did not alter somapacitan dose–IGF-I–response. Mean fixed somapacitan dose after titration was 2.1 mg/week, 1.4 mg/week and 3.8 mg/week, respectively, for patients ≤ 60 years, > 60 years, and female patients taking oral oestrogen. Based on PK/PD analysis, investigated starting doses of 1.5, 1.0 or 2.0 mg/week would result in a mean IGF-I-SDS of −0.4, with approximately 1% and 10% of patients with IGF-I-SDS > 2 and <–2, respectively. Starting doses of 2.0, 1.5 or 4.0 mg/week, would result in a mean IGF-I-SDS of 0.1, with approximately 5% of patients with IGF-I SDS > 2, and 5% with IGF-I-SDS <–2. This approximates the distribution of IGF-I levels in the healthy population. In conclusion, this PK/PD analysis suggests that a starting dose of 1.5 mg/week (1.0–2.0 mg/week) of somapacitan is expected to produce an IGF-I SDS in the lower range of normal, and provides an insight into the theoretical impact of higher starting doses.