Abstract
Disclosure: B.S. Miller: Consulting Fee; Self; Abbvie, Bristol-Myers Squibb, Novo Nordisk, Pfizer, Inc., EMD Serono, Endo Pharmaceuticals. Grant Recipient; Self; Alexion Pharmaceuticals, Inc., Abbvie, Amgen Inc, Novo Nordisk, Pfizer, Inc. J. Blair: Advisory Board Member; Self; Novo Nordisk. Speaker; Self; Novo Nordisk, Ipsen. Other; Self; Novo Nordisk. M. Hojby: Employee; Self; Novo Nordisk. Stock Owner; Self; Novo Nordisk. A.K. Maniatis: Research Investigator; Self; Novo Nordisk, Pfizer, Inc. J. Mori: Advisory Board Member; Self; Novo Nordisk. Speaker; Self; Novo Nordisk, Pfizer, Inc. V. Boettcher: Advisory Board Member; Self; Merck. Speaker; Self; Novo Nordisk, Merck. Other; Self; Ferring Pharmaceuticals, Lilly USA, LLC, Merck, Novo Nordisk. H. Kim: None. R. Beck Bang: Employee; Self; Novo Nordisk. Stock Owner; Self; Novo Nordisk. M. Polak: Advisory Board Member; Self; Ipsen, Novo Nordisk, Pfizer, Inc. Grant Recipient; Self; Ipsen, Novo Nordisk, Pfizer, Inc., Sandoz, Merck, Sanofi. Speaker; Self; Novo Nordisk, Ipsen. R. Horikawa: Advisory Board Member; Self; Novo Nordisk, Pfizer, Inc. Grant Recipient; Self; Sandoz. Speaker; Self; Novo Nordisk, Pfizer, Inc. Growth hormone (GH) has a short half-life that necessitates daily subcutaneous (s.c.) injections for replacement therapy in children with GH deficiency (GHD). Although essential to achieve desired clinical outcomes, daily injections are often burdensome for both patients and their caregivers. Somapacitan (Novo Nordisk A/S) is a long-acting reversible albumin-binding human GH derivative in development for once-weekly s.c. administration in children with GHD, with the aim to overcome the treatment burden of daily injections. REAL4 is an ongoing multi-national, randomized, open labelled phase 3 trial consisting of a 52-week main phase followed by a single-group three-year extension period (NCT03811535). During the main phase, 132 patients received once-weekly 0.16 mg/kg/week somapacitan and 68 received daily GH (0.034 mg/kg/day Norditropin(®), Novo Nordisk). After 52-weeks of treatment, patients in the daily GH group were switched to 0.16 mg/kg/week somapacitan (switch group) while patients receiving somapacitan continued treatment (soma/soma group). 104-week results are presented here. One hundred and ninety-four patients (67 and 127 for switch and soma/soma groups, respectively) completed 104 weeks of treatment. A small, numerical difference was observed at week 52 for mean height velocity (HV) between treatments and this minor difference was sustained from week 52 to 104 (8.7 vs. 8.4 cm/year for the switch and soma/soma groups, respectively). Underlying growth characteristics in year 1 persisted in year 2 for both groups, including when switching to somapacitan, indicating the treatment arm per se did not influence any difference in growth, but rather the baseline characteristics for each group was the cause of the difference. Other height-related endpoints supported these findings, for example a continuous trend towards increased Height SDS was observed in both groups (change from baseline to week 104 of 1.97 and 1.75 for the switch and soma/soma groups, respectively). Pharmacokinetic/pharmacodynamic modelling suggests similar mean average IGF-I SDS levels over the weekly dosing interval within normal range (-2 to +2 SDS) for both groups (0.754 and 0.725 for the switch and soma/soma groups, respectively) in year 2. Somapacitan was well tolerated, with no safety or local tolerability issues identified. There were no clinically relevant findings with respect to changes in glucose metabolism and no neutralizing anti-somapacitan antibodies detected. A low proportion of children reported injection-site reactions in the second year (2.9% and 2.3% in the switch and soma/soma groups, respectively) with no injection site pain reported in either group. In conclusion, once-weekly somapacitan showed sustained efficacy over 2 years and after one year following switch from daily GH treatment with a safety and tolerability profile similar to the well-known profile for daily GH. Presentation: Saturday, June 17, 2023