Somapacitan 10mg/1.5ml solution for injection pre-filled disposable devices

Growth hormone treatment has effectively restored normal growth in children with growth hormone deficiency (GHD); however, it poses challenges in compliance with a daily growth hormone injection regimen, leading to low adherence and persistence rates. Once-weekly Somapacitan is a potential alternative for treating children with GHD. This study aimed to evaluate the efficacy, safety, and adherence of once-weekly subcutaneous Somapacitan compared to daily growth hormone injection in prepubertal children with GHD. A search for the published records was carried out on 17 October 2023 utilizing the searching feature available on PubMed, Embase, and Scopus. Primary study outcomes included (1) efficacy, measured by height velocity (HV), standard deviation score (SDs), height SDs, insulin-like growth factor-SDs (IGF-I SDs), and bone age vs. chronological age ratio (BA vs. CA); (2) safety, assessed through adverse events and injection site reactions; and (3) adherence, determined by the percentage of the sample completing treatments. Secondary outcomes evaluated disease burden scores, divided into three subgroup domains: emotional well-being, physical functional, and social well-being scores. We retrieved 6 studies that were eligible for the systematic review (417 versus 186 for intervention and control, respectively). Only 2 of the total included studies were eligible for pooled analysis (175 versus 82 for intervention and control, respectively). The efficacy profile of Somapacitan was similar to daily growth hormones, indicated by HV (mean difference (MD = 0.04; p = 0.96), HV SDs (MD = −0.71; p = 0.09), height SDs (MD = 0.11; p = 0.69), IGF-I SDs (MD = 0.06; p = 0.70), and CA vs. BA (MD = 0.67; p = 0.70)), demonstrated similar and non-inferior outcomes. Treatment adherence is 3 times higher in the Somapacitan group as compared to control (OR = 3.02; p = 0.03) with adherence rates reaching 95% and 88% for Somapacitan and Norditropin®, respectively. The disease burden measurement is similar in Somapacitan and daily growth hormones (MD = −0.62; p = 0.83), as indicated by the Growth Hormone Deficiency–Child Impact Measure. In almost all outcomes, the level of confidence is strong. The confidence level in the data is generally strong, but for CA vs. BA and the subgroup of severe adverse events with heterogeneity >50%, the confidence level is moderate. Although the efficacy and safety profiles of Somapacitan were found to be similar to those of daily growth hormones, a reduced frequency of once-weekly Somapacitan injections led to increased adherence. PROSPERO registration: CRD42023473209.

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The purpose of this study is to compare the relative efficacy and safety of long-acting growth hormone (LAGH) as a growth hormone replacement therapy in prepubertal children with growth hormone deficiency (GHD). We searched the PubMed, Embase, CNKI, and Wanfang databases from inception to July 2023 and identified eleven relevant studies. PEG-LAGH showed better effect on height velocity (mean difference [MD]: - 0.031, 95% credibility interval [CrI]: - 0.278, 0.215) than somatrogon (MD: 0.105, 95% CrI: - 0.419, 0.636), somapacitan (MD: 0.802, 95% CrI: - 0.451, 2.068) and lonapegsomatropin (MD: 1.335, 95% CrI: - 0.3, 2.989) when compared with daily growth hormone (DGH). Furthermore, in terms of height standard deviation score, PEG-LAGH demonstrated better improvement (MD: - 0.15, 95% CrI: - 1.1, 0.66) than somatrogon (MD: - 0.055, 95% CrI: - 1.3, 0.51) and somapacitan (MD: 0.22, 95% CrI: - 0.91, 1.3). PEG-LAGH (risk ratio [RR]: 1.00, 95% CrI: 0.82, 1.2) reduced the risk of adverse events compared with other LAGH (somatrogon, RR: 1.1, 95% CrI: 0.98, 1.2; somapacitan, RR: 1.1, 95% CrI: 0.96, 1.4; lonapegsomatropin, RR, 1.1, 95% CrI: 0.91, 1.3) and was comparable with DGH. This is the first study to indirectly compare the LAGH thorough a network meta-analysis and provide evidence of the optimal efficacy of various LAGH specifically PEG-LAGH and acceptable safety profile in prepubertal children with GHD.

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Objective To comprehensively compare the efficacy and safety of long-acting human growth hormone (LAGH) preparations with conventional short-acting daily growth hormone (SA-GH) in children with isolated growth hormone deficiency (GHD), and explore potential differences across four distinct LAGH platforms through subgroup analyses. Methods A systematic review and meta-analysis of randomized controlled trials (RCTs) published up to September 2025 was conducted. Five electronic databases [PubMed, Cochrane Library, Web of Science, WanFang Data, and China National Knowledge Infrastructure (CNKI)] were systematically searched without language restrictions. Eligible studies included patients aged <18 years with confirmed GHD (peak GH <10 ng·mL −1 ) and compared any approved once-weekly LAGH preparation with daily SA-GH. Primary outcomes were changes from baseline in height velocity standard deviation score (HV-SDS) and height standard deviation score (Ht-SDS); secondary outcomes included insulin-like growth factor-1 (IGF-1) SDS and adverse events (AEs). Subgroup analyses were performed based on LAGH platform (PEG-LAGH, somatrogon, somapacitan, lonapegsomatropin) and treatment duration. Results A total of 16 RCTs involving 2,435 children (median follow-up: 52 weeks) were included. Overall, compared with SA-GH, LAGH resulted in a modest but statistically significant improvement in first-year Ht-SDS (mean difference [MD]: 0.08; 95% credible interval [CrI]: 0.04–0.11). Numerically, LAGH showed superior HV-SDS compared with SA-GH (MD: 0.85; 95% CrI: −0.39 to 2.09), an effect entirely driven by the PEG-LAGH subgroup (MD: 4.35; 95% CrI: 3.78–4.92). IGF-1 SDS was consistently higher in the LAGH group (MD: 0.51; 95% CrI: 0.21–0.80). AE rates did not differ significantly between groups (LAGH: 31%–46% vs. SA-GH: 35%–50%); the PEG-LAGH subgroup exhibited the lowest AE incidence (31.1%). Conclusions Among children with isolated GHD, LAGH represents the preferred platform, offering both superior first-year height velocity and acceptable safety. In contrast, newer prodrug or albumin-binding LAGH formulations provide injection convenience but lack superior growth efficacy.

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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.

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Randomised, double-blind, crossover trial to confirm bioequivalence of somapacitan, a long-acting growth hormone (GH), in 5 mg/1.5 mL and 10 mg/1.5 mL strengths in equimolar doses. Healthy participants were randomised (1:1:1) to subcutaneous somapacitan treatment in one dosing period with 5 mg/1.5 mL and two periods with 10 mg/1.5 mL. Eligibility criteria included age 18–45 years and body mass index 18.5–24.9 kg/m2. Exclusion criteria included history of GH deficiency, previous GH treatment, weight > 100.0 kg and participation in any clinical trial of an investigational medicinal product within 45 days or five times the half-life of the previous investigational product before screening. Area under the curve from time 0 until last quantifiable observation (AUC0–t), maximum serum concentration (Cmax), time to Cmax and terminal half-life of somapacitan and safety were assessed. In total, 33 participants were randomised. For AUC0–t, estimated treatment ratio (ETR) (5 mg/1.5 mL versus 10 mg/1.5 mL) was 0.95 (90% confidence interval [CI] 0.89–1.01). Point estimate and 90% CIs were within the acceptance range (0.80–1.25). For Cmax, ETR was 0.77 (90% CI 0.68–0.89). Point estimate and 90% CIs were outside the acceptance range (0.80–1.25). Mean insulin-like growth factor-I (IGF-I) and IGF-I standard deviation score concentration–time curves for each strength were almost identical. No new safety issues were identified. Bioequivalence criterion for somapacitan 5 mg/1.5 mL and 10 mg/1.5 mL was met for AUC0–t but not for Cmax. The two strengths had equivalent IGF-I responses. ClinicalTrials.gov, NCT03905850 (3 April 2019). Somapacitan is a long-acting growth hormone used to treat people with growth hormone deficiency. Somapacitan is injected under the skin with an injection pen. The dose is based on a person’s body weight and how they respond to treatment. We compared two strengths of injection pen, containing either 5 or 10 mg of somapacitan per 1.5 mL. For both strengths, participants were given the same dose. We wanted to understand whether the body absorbs these different strengths into the bloodstream in the same way. We also measured levels of insulin-like growth factor-I (IGF-I), a hormone formed when growth hormone is present in the blood, to see the effect of different strengths of somapacitan on the body. In our study, 33 healthy adults received one round of injection using the somapacitan 5 mg pen and two rounds using the somapacitan 10 mg pen, all at least 3 weeks apart. We found no differences in the amount of somapacitan being absorbed into the bloodstream, nor how fast it was absorbed. The peak amount of somapacitan in the bloodstream was higher in people using the 10 mg pen. There were no differences in IGF-I levels following use of either injection pen. Overall, our results show both strengths of somapacitan lead to similar responses in the body. Having different strength options could allow doctors to adjust the dose of somapacitan more easily, depending on a patient’s response to treatment.

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CONTEXT: Growth hormone deficiency (GHD) in children is currently treated with daily injections of GH, which can be burdensome for patients and their parents/guardians. Somapacitan is a GH derivative in development for once-weekly treatment of GHD. OBJECTIVE: This work aimed to assess the efficacy and safety of somapacitan, and associated disease/treatment burden, after 4 years of treatment and 1 year after switching to somapacitan from daily GH. METHODS: This long-term safety extension of a multicenter, controlled phase 2 trial (NCT02616562) took place at 29 sites in 11 countries. Patients were prepubertal, GH-naive children with GHD. Fifty patients completed 4 years of treatment. Patients in the pooled group received somapacitan (0.04, 0.08, 0.16 mg/kg/week) for 1 year, followed by the highest dose (0.16 mg/kg/week) for 3 years. Patients in the switched group received daily GH 0.034 mg/kg/day for 3 years, then somapacitan 0.16 mg/kg/week for 1 year. Main outcome measures were height velocity (HV), change from baseline in HV SD score (SDS), change from baseline in height SDS, disease burden, and treatment burden for patients and parents/guardians. RESULTS: Changes from baseline in HV and HV SDS were similar and as expected in both groups. Observer-reported outcomes showed that patients and parents/guardians seem to have experienced a reduced treatment burden when switching from daily GH to somapacitan. Most parents/guardians (81.8%) strongly/very strongly preferred somapacitan over daily GH. CONCLUSIONS: Somapacitan showed similar efficacy and safety in patients who continued somapacitan treatment and those who switched from daily GH to somapacitan. Once-weekly injections may lead to a reduced treatment burden relative to once-daily injections. A plain-language summary of this work is available.

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CONTEXT: Somapacitan is a long-acting GH derivative for treatment of GH deficiency (GHD). OBJECTIVE: Evaluate the efficacy and tolerability of somapacitan in children with GHD after 2 years of treatment and after the switch from daily GH. DESIGN: A randomized, multinational, open-labelled, controlled parallel group phase 3 trial, comprising a 52-week main phase and 3-year safety extension (NCT03811535). SETTING: Eighty-five sites across 20 countries. PATIENTS: A total of 200 treatment-naïve prepubertal patients were randomized and exposed; 194 completed the 2-year period. INTERVENTIONS: Patients were randomized 2:1 to somapacitan (0.16 mg/kg/wk) or daily GH (0.034 mg/kg/d) during the first year, after which all patients received somapacitan 0.16 mg/kg/wk. MAIN OUTCOME MEASURES: Height velocity (HV; cm/year) at week 104. Additional assessments included HV SD score (SDS), height SDS, IGF-I SDS, and observer-reported outcomes. RESULTS: HV was sustained in both groups between 52 and 104 weeks. At week 104, mean (SD) for HV between weeks 52 and 104 was 8.4 (1.5) cm/year after continuous somapacitan treatment and 8.7 (1.8) cm/year after 1 year of somapacitan treatment following switch from daily GH. Secondary height-related endpoints also supported sustained growth. Mean IGF-I SDS during year 2 was similar between groups and within normal range (-2 to +2). Somapacitan was well tolerated, with no safety or tolerability issues identified. GH patient preference questionnaire results show that most patients and their caregivers (90%) who switched treatment at year 2 preferred once-weekly somapacitan over daily GH treatment. CONCLUSIONS: Somapacitan in children with GHD showed sustained efficacy and tolerability for 2 years, and after switching from daily GH. Patients/caregivers switching from daily GH expressed a preference for somapacitan. CLINICAL TRIAL REGISTRATION: NCT03811535.

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OBJECTIVE: Somapacitan is a long-acting growth hormone (GH) derivative developed for the treatment of GH deficiency (GHD). This study evaluates the efficacy and tolerability of somapacitan in Japanese children with GHD after 104 weeks of treatment and after switch from daily GH. DESIGN: Subanalysis on Japanese patients from a randomised, open-labelled, controlled parallel-group phase 3 trial (REAL4, NCT03811535). PATIENTS AND MEASUREMENTS: Thirty treatment-naïve patients were randomised 2:1 to somapacitan (0.16 mg/kg/week) or daily GH (0.034 mg/kg/day) up to Week 52, after which all patients received somapacitan. Height velocity (HV; cm/year) at Weeks 52 and 104 were the primary measurements. Additional assessments included HV SD score (SDS), height SDS, bone age, insulin-like growth factor-I (IGF-I) SDS, and observer-reported outcomes. RESULTS: At Week 52, observed mean HV was similar between treatment groups (10.3 vs. 9.8 cm/year for somapacitan and daily GH, respectively). Similar HVs between groups were also observed at Week 104: 7.4 cm/year after continuous somapacitan treatment (soma/soma) and 7.9 cm/year after 1-year somapacitan treatment following switch from daily GH (switch). Other height-related endpoints supported continuous growth. IGF-I SDS increased in both groups with mean IGF-I SDS within -2 and +2 during the study. Somapacitan was well tolerated, one mild injection site reaction was reported, with no reports of injection site pain. Patient preference questionnaires showed that most patients and their caregivers (90.9%) who switched treatment at Week 52 preferred once-weekly somapacitan over daily GH treatment. CONCLUSIONS: Somapacitan showed sustained efficacy in Japanese children with GHD over 104 weeks and for 52 weeks after switching from daily GH. Somapacitan was well tolerated and preferred over daily GH.

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Abstract: Growth hormone (GH) replacement therapy for growth hormone deficiency (GHD) in children and adults has for over 25 years, until recently, been administered as daily injections. This daily treatment regimen often incurs a burden to patients and caregivers, leading to high rates of non-adherence and, consequently, decreased treatment efficacy outcomes. To address this shortcoming, long-acting growth hormones (LAGHs) have been developed with the aim of reducing the burden of daily injections, thereby potentially improving treatment adherence and outcomes. Somapacitan (Sogroya ® ) (Novo Nordisk, Bagsværd, Denmark) is a LAGH currently approved for the treatment of adult and childhood GHD (AGHD and CGHD, respectively) in several countries. Other LAGHs, such as somatrogon (Ngenla ® ) (Pfizer, New York, United States) and lonapegsomatropin/TransCon GH (Skytrofa ® ) (Ascendis Pharma, Copenhagen, Denmark), are also currently approved and available for the treatment of CGHD in several countries. In this review, we will consider the method of protraction, pharmacokinetics (PK) and pharmacodynamics (PD), efficacy, and safety results of somapacitan in adult and pediatric trials and how these characteristics differ from those of the other aforementioned LAGHs. Additionally, the administration of somapacitan and timing of measurement of serum insulin-like growth factor-I (IGF-I) levels are summarized. Information on administration, advice on missed doses, and clinical guidelines are discussed, as well as identifying which patients are suitable for somapacitan therapy, and how to monitor and adjust dosing whilst on therapy. Keywords: (3– 6): growth hormone, long-acting growth hormone, adult growth hormone deficiency, pediatric growth hormone deficiency, adherence

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