Somatrogon 60mg/1.2ml solution for injection pre-filled disposable devices

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 Long-acting growth hormone (LAGH) has the potential to improve adherence and outcomes over daily somatropin in growth hormone deficiency (GHD). Whereas daily somatropin products are molecularly identical, LAGHs are molecularly distinct; additional moieties or mechanisms that prolong LAGH action confer unique pharmacodynamic/pharmacokinetic properties that could affect efficacy and safety. Only one LAGH available in the United States and Europe (lonapegsomatropin) delivers unmodified somatropin. With no head-to-head clinical trials of LAGHs available, this systematic literature review and network meta-analysis were conducted to compare the relative efficacy and safety of LAGHs in pediatric GHD. Five trials were eligible for inclusion in a Bayesian network meta-analysis; 3 contributed to the base case network, including 3 LAGHs (lonapegsomatropin, somapacitan, and somatrogon) and daily somatropin. Treatment with lonapegsomatropin was associated with statistically significantly higher annualized height velocity and change from baseline in height SD score (SDS) at week 52 compared to daily somatropin and somapacitan; no other significant differences in these outcomes were found. The change from baseline in average insulin-like growth factor-1 (IGF-1) SDS at week 52 was significantly higher for somatrogon vs all comparators and for lonapegsomatropin vs daily somatropin and somapacitan; average IGF-1 SDS was within normal range in all trials. No significant differences were seen in progression in bone age-to-chronological age ratio or serious adverse events (SAEs). Sensitivity analyses were consistent with the base case. In this network meta-analysis, lonapegsomatropin was the only LAGH associated with better growth outcomes. No significant differences were detected regarding SAEs; other safety outcomes could not be analyzed.

Abstract licence: CC BY

Growth hormone (GH) is crucial for childhood growth and body composition. In pediatric GH deficiency (pGHD), the pituitary gland fails to produce sufficient GH, which affects linear growth in childhood. pGHD is conventionally treated with daily recombinant human GH (rhGH); however, because GH therapy lasts throughout childhood, adherence to daily rhGH treatment can be low, resulting in suboptimal effectiveness. Somatrogon is a long-acting GH analog designed to address the challenges associated with daily GH therapy for pGHD. Somatrogon administered once per week is a potential alternative to daily GH therapy. The use of somatrogon is supported by phase II and III clinical trials demonstrating that once-weekly injections are noninferior to once-daily somatropin injections in terms of efficacy, safety, and tolerability and have the advantage of reduced treatment burden. This review summarizes the clinical trials of somatrogon and discusses the therapeutic profile and effects of treating pGHD with reduced injection frequency.

Abstract licence: CC BY-NC 4.0

From the perspective of clinical pediatric endocrinology, progress in molecular biology over the past few decades has improved our understanding of growth physiology. This progress was particularly conspicuous in the early era of Sanger-based sequencing and has continued into the current era of next-generation sequencing. The first half of this review summarizes the current understanding about growth. The latter half discusses the development of long-acting GH (LAGH), an important, recent topic in pediatric endocrinology, with a focus on the Japanese market. LAGH is administered weekly over several years in some developed countries as treatment for GH deficiency (GHD). In Japan, somatrogon and somapacitan are available, and lonapegsomatropin has completed a clinical trial. As per recent meta-analyses, these three products were not inferior to conventional, daily GH therapy for short-term growth in pediatric GHD. Although LAGH is promising, some concerns remain. Well-designed clinical research is needed to expand the indications for LAGH to other conditions, such as idiopathic short stature. Finally, future research on orally administered agents may open new avenues for the treatment of short stature.

Abstract licence: CC BY-NC-ND

Abstract Context Somatrogon is a long-acting recombinant human growth hormone (rhGH) in development for once-weekly treatment of children with growth hormone deficiency (GHD). Objective We aimed to compare the efficacy and safety of once-weekly somatrogon with once-daily somatropin in prepubertal children with GHD. Methods In this 12-month, open-label, randomized, active-controlled, parallel-group, phase 3 study, participants were randomized 1:1 to receive once-weekly somatrogon (0.66 mg/kg/week) or once-daily somatropin (0.24 mg/kg/week) for 12 months. A total of 228 prepubertal children (boys aged 3-11 years, girls aged 3-10 years) with GHD, impaired height and height velocity (HV), and no prior rhGH treatment were randomized and 224 received ≥1 dose of study treatment (somatrogon: 109; somatropin: 115). The primary endpoint was annualized HV at month 12. Results HV at month 12 was 10.10 cm/year for somatrogon-treated subjects and 9.78 cm/year for somatropin-treated subjects, with a treatment difference (somatrogon-somatropin) of 0.33 (95% CI: −0.24, 0.89). The lower bound of the 2-sided 95% CI was higher than the prespecified noninferiority margin (−1.8 cm/year), demonstrating noninferiority of once-weekly somatrogon vs daily somatropin. HV at month 6 and change in height standard deviation score at months 6 and 12 were similar between both treatment groups. Both treatments were well tolerated, with a similar percentage of subjects experiencing mild to moderate treatment-emergent adverse events in both groups (somatrogon: 78.9%, somatropin: 79.1%). Conclusion The efficacy of once-weekly somatrogon was noninferior to once-daily somatropin, with similar safety and tolerability profiles. (ClinicalTrials.gov no. NCT02968004).

Abstract licence: CC BY-NC-ND 4.0

Abstract Objectives Somatrogon is a long-acting recombinant human growth hormone (GH) employed as a once-weekly treatment for children with GH deficiency (GHD). A 12-month, phase 2 study of once-weekly somatrogon vs. once-daily GH (Genotropin®) was initiated, after which participants could enroll into an open-label extension (OLE) evaluating the safety and efficacy of long-term somatrogon treatment. Methods There were five study periods, Periods I and II were 6 months each while Periods III, IV, and V were 12 months each. In the main study (Periods I and II), 53 prepubertal children with GHD were randomized to once-weekly somatrogon (0.25, 0.48, or 0.66 mg/kg/week) or once-daily Genotropin (0.034 mg/kg/day); 48 continued into the OLE, consisting of Period III (original somatrogon dose; Genotropin recipients randomized to one of three somatrogon doses), Period IV (somatrogon 0.66 mg/kg/week), and Period V (prefilled somatrogon pen [0.66 mg/kg/week]). Results At the end of Period III, the mean ± SD annual height velocity (HV) for 0.25, 0.48, and 0.66 mg/kg/week somatrogon groups was 7.73 ± 1.89, 7.54 ± 1.28, and 8.81 ± 1.12 cm/year, respectively; HV was sustained during Periods IV/V. Height SD scores (SDS) showed progressive improvement throughout the OLE, regardless of initial cohort assignment, approaching the normal range (−0.69 ± SD 0.87) at the end of Period V Year 1. Mild or moderate treatment-emergent adverse events were reported in 81.3% of participants, most unrelated to study drug. Conclusions Up to 5 years of once-weekly somatrogon was well tolerated and resulted in sustained improvement in height SDS and delta height SDS in prepubertal short children with GHD.

Abstract licence: CC BY 4.0

Abstract Objective Treatment of pediatric growth hormone deficiency (pGHD) with daily injection of recombinant human growth hormone (somatropin) aims to increase height velocity and improve health-related quality of life (HRQoL). The Quality of Life in Short Stature Youth (QoLISSY) questionnaire was administered in a phase 3 clinical trial that evaluated efficacy and safety of once-weekly somatrogon versus once-daily somatropin in children with pGHD (ClinicalTrials.gov no NCT02968004). Methods Treatment-naïve prepubertal children with pGHD received once-weekly somatrogon or once-daily somatropin for 12 months. The QoLISSY core module (physical/social/emotional subscales) was administered at baseline and 12 months after treatment initiation. QoLISSY-Parent was completed by parents/caregivers of children <7 years old and some parents/caregivers of children ≥7 years old; children ≥7 years old self-completed QoLISSY-Child. Results Baseline characteristics were similar between treatment groups (N = 117). Among children <7 years old, QoLISSY-Parent total and subscale scores showed similarly improved HRQoL at 12 months relative to baseline in both treatment groups. Self-reported QoLISSY-Child total and subscale scores in children ≥7 years old indicated HRQoL improvements at 12 months that were numerically better with somatrogon than somatropin (similar results with QoLISSY-Parent in this age group). At both time points, children reported better HRQoL than perceived by their parents/caregivers. Conclusion Treatment for 12 months with once-weekly somatrogon or once-daily somatropin resulted in comparable improvements in HRQoL among children with pGHD. Lower HRQoL perceived by parents/caregivers possibly reflect children’s tendency to emphasize adaptation. These results suggest that evaluation of HRQoL could help support treatment decisions in children with pGHD treated with growth hormone. PLAIN LANGUAGE SUMMARY Pediatric growth hormone deficiency is a condition that causes slow growth. Children with this condition have height that is lower than normal unless the condition is treated. The slow growth and short height may have bad effects on the emotional and social well-being of these children. Treatment usually consists of a growth hormone that is administered by daily injection under the skin over a period of years. However, children and their parents may not like these daily injections and often stop treatment. A newer treatment is available that can be injected once weekly. This newer treatment increases growth the same as daily injections. We looked at whether 12 months of treatment given once a week has the same positive effects on the physical, social, and emotional health of children as the daily treatment. Children and their parents answered questions that asked how being short affects the physical, social, and emotional parts of their life. These questions were asked before starting treatment and 12 months after starting treatment. In children younger than 7 years old, improvements at 12 months in their physical, social, and emotional health were similar between the treatments. In children 7 years old or older, those who received the once-weekly injections had slightly better improvements than those who received the daily injections. These results can help parents and doctors make decisions about treating children with pediatric growth hormone deficiency.

Abstract licence: CC BY-NC-ND 4.0