Somapacitan 15mg/1.5ml solution for injection pre-filled disposable devices

Abstract Disclosure: A.B. Pinheiro: None. A.M. de Almeida: None. I.J. Aguiar: None. D.M. Ribeiro: None. C.L. Welter: None. G.N. Maffezoli: None. J. Juliasse: None. B.R. Lopes: None. A.S. Silva: None. A.S. Zapala: None. Background: Growth hormone deficiency (GHD) in pre-pubertal children is commonly treated with daily growth hormone (GH) injections. However, daily treatment can lead to low treatment adherence. Weekly long-acting growth hormone (Somapacitan) has been proposed as a potential alternative. This meta-analysis aims to compare the efficacy and safety of daily GH therapy versus weekly Somapacitan in children with GHD. Materials and Methods: PubMed, Embase, and Cochrane databases were searched for randomized controlled trials (RCTs) comparing daily GH with weekly Somapacitan for GHD in prepubertal children on December 02, 2024. Data were analyzed using a random-effects model, and Risk Ratio (RR) and Mean Differences (MD) with 95% confidence intervals (CI) were calculated. Heterogeneity was assessed using I² statistics. Statistical analysis was performed using R, version 4.4.2. Results: 3 RCTs involving 319 participants were included, of whom 212 (66.45%) received weekly Somapacitan. A statistically significant difference was observed in the Height Velocity Standard Deviation Score (HVSDS), with Somapacitan demonstrating a greater effect on height velocity compared to daily GH (MD -0.90; 95% CI -1.67 to -0.14; p = 0.021). Notably, the negative value of the MD indicates that Somapacitan improved height velocity more than GH, as reflected in the leftward shift on the graph. No significant differences were observed between the groups in changes in Insulin-like Growth Factor-I (IGF-I) (MD -0.53; 95% CI -1.45 to 0.40; p = 0.262), Height Standard Deviation Score (HSDS) (MD -0.11; 95% CI -0.24 to 0.02; p = 0.087), or total adverse events (RR 1.02; 95% CI 0.83 to 1.24; p = 0.878). Additionally, no significant differences were found in the rates of mild (RR 1.04; 95% CI 0.80 to 1.36; p = 0.748) or moderate adverse events (RR 1.37; 95% CI 0.81 to 2.32; p = 0.238). Conclusion: Results of this systematic review and meta-analysis suggest that Somapacitan had no significant effect on IGF-I, HSDS, or total adverse events. However, a significant improvement in height velocity was observed, with Somapacitan showing greater efficacy in increasing height velocity compared to daily GH treatment. Presentation: Saturday, July 12, 2025

Abstract licence: CC BY-NC-ND 4.0

Since direct comparisons of long-acting growth hormones (LAGHs) are lacking, analyses were performed to indirectly compare the efficacy and safety of somapacitan versus somatrogon and lonapegsomatropin in children with growth hormone deficiency (GHD). A systematic literature review (SLR) identified studies of once-weekly LAGHs for the treatment of pediatric GHD. Indirect comparisons (ICs) using a Bayesian hierarchical network meta-analysis and a random effects model were performed using daily growth hormone (GH) 0.034 mg/kg/day (base case) or 0.024–0.034 mg/kg/day (alternative analyses) as the common comparator to compare height outcomes to 52 weeks [annualized height velocity, height velocity standard deviation score (SDS), and height SDS]. Identified evidence did not allow IC of safety or longer-term efficacy outcomes so these were qualitatively described. The SLR identified two somapacitan trials, three somatrogon trials (one included in alternative analyses only), and one lonapegsomatropin trial comparing the LAGH with daily GH in treatment-naïve pre-pubertal children for IC. ICs revealed no differences at 52 weeks between somapacitan versus somatrogon and lonapegsomatropin, as well as daily GH, with respect to all growth outcomes considered in children with GHD. All three LAGHs had sustained efficacy and were generally well tolerated, with comparable efficacy and safety to daily GH, with the exception of observed injection site pain for somatrogon. No efficacy and safety differences were identified in comparisons of once weekly somapacitan versus somatrogon and lonapegsomatropin, as well as daily GH. All treatments were generally well tolerated, with the exception of observed injection site pain for somatrogon. It is valuable to compare similarly acting treatments to determine their relative benefits and risks. Direct comparisons of long-acting growth hormones (LAGHs) are lacking, so analyses were performed to indirectly compare the efficacy and safety of the LAGH somapacitan versus the LAGHs somatrogon and lonapegsomatropin in children with growth hormone deficiency. Studies of once-weekly LAGHs for the treatment of pediatric growth hormone deficiency were identified using a systematic literature review, then the data obtained were indirectly compared using standard statistical methods with daily growth hormone 0.034 mg/kg/day (base case) or 0.024–0.034 mg/kg/day (alternative analyses) as the common comparator. Height outcomes to 52 weeks (annualized height velocity, height velocity standard deviation score, and height standard deviation score) were compared between treatments. Sufficient information to allow indirect comparison of safety or longer-term efficacy outcomes were not found so these were qualitatively described. The systematic literature review identified two somapacitan trials, three somatrogon trials (one included in alternative analyses only) and one lonapegsomatropin trial comparing the LAGH with daily growth hormone in previously untreated pre-pubertal children for inclusion in the indirect comparison. Indirect comparisons identified no differences to 52 weeks between somapacitan versus somatrogon and lonapegsomatropin, as well as daily growth hormone, with respect to all growth outcomes considered in children with growth hormone deficiency. All three LAGHs had sustained efficacy and were generally well tolerated, with comparable efficacy and safety to daily growth hormone, with the possible exception of injection site pain with somatrogon.

Abstract licence: CC BY-NC 4.0

BackgoundThe purpose of this study is to compare the effect of long-acting growth hormone (LAGH) to daily GH on body mass index (BMI) in children with growth hormone deficiency (GHD).MethodsWe searched the PubMed database from its inception to July 2025 and identified three relevant randomized controlled trials lasting over 6 months, with extension phases providing longitudinal BMI data. Longitudinal BMI data were available for lonapegsomatropin, somatrogon, and somapacitan, but not for polyethylene glycol LAGH.ResultsA total of 585 patients were included in the present analysis, of which 346 were in the LAGH group, and 239 were in the daily rhGH group, derived from seven original articles and two abstracts/ePosters. At 12 months, there was a significant difference in BMI SD scores between LAGH and daily GH groups (Mean difference [MD] 0.66 SDS [95% confidence interval [CI] 0.04-1.29]). BMI SDS significantly increased in the LAGH group (MD + 0.41 SDS [95% CI 0.04-0.77] from 0 to 12 months), whereas it did not change in the daily GH group (MD -0.35 SDS [95% CI -0.76 to +0.07] from 0 to 12 months). Between 12 and 24 months, after switching from daily GH to LAGH (daily GH/LAGH), or pursuing LAGH (LAGH/LAGH) in the extension phases of the studies, BMI SDS significantly increased in the daily GH/LAGH switching group (MD + 0.75 SDS [95% CI 0.24-1.27] from 12 to 24 months), whereas it remained steady in the LAGH/LAGH group. Omitting one study at a time from the meta-analysis did not materially affect the results.ConclusionAn increase in body mass index SD score is associated with the first year of LAGH use.

Abstract licence: CC BY

Abstract Context Growth hormone (GH) replacement requires daily GH injections, which is burdensome for some adult patients with GH deficiency (AGHD). Objective To demonstrate efficacy and safety of somapacitan, a once-weekly reversible albumin-binding GH derivative, versus placebo in AGHD. Design Randomized, parallel-group, placebo-controlled (double-blind) and active-controlled (open-label) phase 3 trial, REAL 1 (NCT02229851). Setting Clinics in 17 countries. Patients Treatment-naïve patients with AGHD (n = 301 main study period, 272 extension period); 257 patients completed the trial. Interventions Patients were randomized 2:2:1 to once-weekly somapacitan, daily GH, or once-weekly placebo for 34 weeks (main period). During the 52-week extension period, patients continued treatment with somapacitan or daily GH. Main outcome measures Body composition measured using dual-energy x-ray absorptiometry (DXA). The primary endpoint was change in truncal fat percentage to week 34. Insulin-like growth factor 1 (IGF-I) standard deviation score (SDS) values were used to dose titrate. Results At 34 weeks, somapacitan significantly reduced truncal fat percentage (estimated difference: −1.53% [−2.68; −0.38]; P = 0.0090), demonstrating superiority compared with placebo, and it improved other body composition parameters (including visceral fat and lean body mass) and IGF-I SDS. At 86 weeks, improvements were maintained with both somapacitan and daily GH. Somapacitan was well tolerated, with similar adverse events (including injection-site reactions) compared with daily GH. Conclusions In AGHD patients, somapacitan administered once weekly demonstrated superiority over placebo, and the overall treatment effects and safety of somapacitan were in accordance with known effects and safety of GH replacement for up to 86 weeks of treatment. Somapacitan may provide an effective alternative to daily GH in AGHD. A short visual summary of our work is available (1).

Abstract licence: CC BY 4.0

Objective Somapacitan is a reversible albumin-binding growth hormone (GH) derivative, developed for once-weekly administration. This study aimed to evaluate the safety of once-weekly somapacitan vs once-daily Norditropin®. Local tolerability and treatment satisfaction were also assessed. Design 26-week randomized, controlled phase 3 safety and tolerability trial in six countries (Nbib2382939). Methods Male or female patients aged 18–79 years with adult GH deficiency (AGHD), treated with once-daily GH for ≥6 months, were randomized to once-weekly somapacitan (n = 61) or once-daily Norditropin (n = 31) administered subcutaneously by pen. Both treatments were dose titrated for 8 weeks to achieve insulin-like growth factor I (IGF-I) standard deviation score (SDS) levels within the normal range, and then administered at a fixed dose. Outcome measures were adverse events (AEs), including injection site reactions; occurrence of anti-somapacitan/anti-GH antibodies and change in treatment satisfaction, assessed using the Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9). Results Mean IGF-I SDS remained between 0 and 2 SDS throughout the trial in both groups. AEs were mostly mild or moderate and transient in nature. The most common AEs were nasopharyngitis, headache and fatigue in both groups. More than 1500 somapacitan injections were administered and no clinically significant injection site reactions were reported. No anti-somapacitan or anti-GH antibodies were detected. The TSQM-9 score for convenience increased significantly more with somapacitan vs Norditropin (P = 0.0171). Conclusions In this 26-week trial in patients with AGHD, somapacitan was well tolerated and no safety issues were identified. Once-weekly somapacitan was reported to be more convenient than once-daily Norditropin.

Abstract licence: CC BY 4.0

Abstract Context Somapacitan, a once-weekly reversible albumin-binding GH derivative, is evaluated in children with GH deficiency (GHD). Objective To demonstrate efficacy and safety of somapacitan vs daily GH. Methods REAL4 is a randomised, multinational, open-labeled, active-controlled parallel group phase 3 trial, comprising a 52-week main trial and 3-year extension (NCT03811535). Setting Eighty-six sites across 20 countries. Patients 200 treatment-naïve patients were randomized and exposed. Interventions Patients were randomized 2:1 to somapacitan (0.16 mg/kg/wk) or daily GH (Norditropin; 0.034 mg/kg/d), administered subcutaneously. Main outcome measures The primary endpoint was annualized height velocity (HV; cm/y) at week 52. Additional assessments included HV SD score (SDS), height SDS, bone age, IGF-I SDS, patient-reported outcomes, and safety measures. Results Estimated mean HV at week 52 was 11.2 and 11.7 cm/y for somapacitan and daily GH, respectively. Noninferiority was confirmed. Changes in HV SDS, height SDS, bone age, and IGF-I SDS from baseline to week 52 were similar between treatment groups. At week 52, mean IGF-I SDS values were similar between treatment groups and within normal range (–2 to +2). Safety of somapacitan was consistent with the well-known daily GH profile. Low proportions of injection-site reactions were reported for somapacitan (5.3%) and daily GH (5.9%). Both treatments similarly reduced disease burden from baseline to week 52, whereas a greater treatment burden reduction was observed for somapacitan. Conclusions Similar efficacy for somapacitan compared to daily GH was demonstrated over 52 weeks of treatment with comparable safety and mean IGF-I SDS levels in treatment-naïve children with GHD.

Abstract licence: CC BY-NC-ND 4.0

Abstract Context Daily growth hormone (GH) injections can be burdensome for patients and carers. Somapacitan is a long-acting, reversible albumin-binding GH derivative in development for once-weekly administration in patients with growth hormone deficiency (GHD). Objective The objective of this study is to evaluate the efficacy, safety, and tolerability of once-weekly somapacitan vs once-daily GH. Design REAL 3 is a multicenter, randomized, controlled, double-blind (somapacitan doses), phase 2 study with a 26-week main and 26-week extension phase (NCT02616562). Setting This study took place at 29 sites in 11 countries. Patients Fifty-nine GH treatment-naive prepubertal children with GHD were randomly assigned; 58 completed the trial. Interventions Interventions comprised 3 somapacitan doses (0.04 [n = 16], 0.08 [n = 15], or 0.16 mg/kg/wk [n = 14]) and daily GH (0.034 mg/kg/d [n = 14]), administered subcutaneously. Main Outcome Measures The primary end point was height velocity (HV) at week 26. Secondary efficacy end points included HV SD score (SDS) and insulin-like growth factor-I (IGF-I) SDS. Results At week 26, mean (SD) annualized HV for the somapacitan groups was 8.0 (2.0), 10.9 (1.9), and 12.9 (3.5) cm/year, respectively, vs 11.4 (3.3) cm/year for daily GH; estimated treatment difference (somapacitan 0.16 mg/kg/week—daily GH): 1.7 [95% CI –0.2 to 3.6] cm/year. HV was sustained at week 52, and significantly greater with somapacitan 0.16 mg/kg/week vs daily GH. Mean (SD) change from baseline in HV SDS at week 52 was 4.72 (2.79), 6.14 (3.36), and 8.60 (3.15) for the somapacitan groups, respectively, vs 7.41 (4.08) for daily GH. Model-derived mean (SD) IGF-I SDS for the somapacitan groups was −1.62 (0.86), −1.09 (0.78), and 0.31 (1.06), respectively, vs −0.40 (1.50) observed for daily GH. Safety and tolerability were consistent with the profile of daily GH. Conclusions In children with GHD, once-weekly somapacitan 0.16 mg/kg/week provided the closest efficacy match with similar safety and tolerability to daily GH after 26 and 52 weeks of treatment. A short visual summary of our work is available (1).

Abstract licence: CC BY 4.0