Somatrogon
Growth hormone fused to a hormone tail so one injection lasts a week, for children with GH deficiency
Somatrogon is human growth hormone joined to copies of a short C-terminal peptide from hCG, which slows its clearance enough for weekly dosing. Pfizer's Ngenla was approved in the US on June 27, 2023 for children 3 and older with growth failure from growth hormone deficiency.
What is it?
Somatrogon replaces 365 daily injections a year with 52 weekly ones. It is human growth hormone fused to copies of the C-terminal peptide of hCG, whose sugar-coated tails shield it from filtration by the kidneys; the label gives an effective half-life of 37.7 hours.
The dose came from the phase 2 MOD-4023 study, in which IGF-I rose with dose without exceeding +2 SDS and 0.66 mg/kg a week came closest to daily growth hormone. In the pivotal trial, 228 prepubertal children with growth hormone deficiency grew 10.10 cm a year on that dose against 9.78 on daily somatropin, meeting non-inferiority.
Longer follow-up holds up. In the pivotal trial's extension, children kept growing about 8 cm a year in years one and two, and those switched from daily somatropin did as well as those treated from the start; up to a quarter needed a dose cut for high IGF-I. The original phase 2 cohort, followed for nine years, moved from a height SDS of -4.0 to -0.2, and a Japanese extension reported similar gains over four years.
Real-world reports add two points. One cohort found weight gain: BMI z-scores rose faster on weekly somatrogon than on daily treatment in the first six months. And reports to the FDA and WHO databases cluster on injection-site reactions, device problems and IGF-I abnormalities, mostly within the first month.
Comparisons outside trials point the same way. Matched against 155 children on daily somatropin in the KIGS registry, children from the phase 3 study grew at similar rates over three years. Injection pain is the commonest complaint: in 19 children who reported it, switching to somapacitan cut pain scores from 6.5 to 1.6, though in an unblinded, single-arm study.
In adults the picture is less settled: a 2026 trial in 198 adults normalised IGF-I but missed its primary trunk-fat endpoint, though lean mass improved, and the US label covers only children 3 and older.
Its warnings are growth hormone's own: intracranial hypertension, fluid retention, glucose intolerance and diabetes, slipped capital femoral epiphysis and worsening scoliosis, with contraindications in acute critical illness, active cancer and closed growth plates.
Somatrogon is one of three weekly growth hormones, alongside somapacitan, which binds albumin, and lonapegsomatropin, which releases unmodified somatropin from a carrier.
Mechanism of Action
Somatrogon acts as growth hormone does; its hCG-derived tails keep it circulating for days.
Growth hormone receptor
Binds the GH receptor like somatropin, activating JAK2/STAT5 signalling and IGF-I production (dataset mechanism).
CTP tails
Copies of hCG's O-glycosylated C-terminal peptide shield the protein from kidney filtration and breakdown (dataset mechanism).
Weekly profile
Effective half-life 37.7 hours (Ngenla label 12.3).
Published Research
The trials behind somatrogon, read from their PubMed abstracts: the dose-finding and pivotal paediatric trials with their three-, four- and nine-year follow-ups, real-world and pharmacovigilance reports, and the adult trial. Dosing from the Ngenla label read October 1, 2026.
Weekly against daily in children
In 228 prepubertal children with GHD, height velocity at 12 months was 10.10 cm a year on somatrogon 0.66 mg/kg weekly and 9.78 on daily somatropin, meeting non-inferiority.
Phase 3 extension: three years
In the open-label extension of the pivotal trial, height velocity was 8.11 and 7.91 cm a year in years 1 and 2 and height SDS rose to -0.95; children switched from daily somatropin grew as well as those on somatrogon throughout. Up to a quarter had IGF-I SDS above 2 twice running, meeting the criterion for a dose cut.
Finding the dose
In the phase 2 MOD-4023 study, IGF-I rose with dose without exceeding +2 SDS, all cohorts showed catch-up growth, 0.66 mg/kg a week came closest to daily growth hormone, and there were no serious adverse events.
Nine years in the phase 2 cohort
In the phase 2 cohort's open-label follow-up, height SDS rose from -4.0 at baseline to -0.2 by year 8 with height velocity above 5 cm a year; adverse events fell from 52.1% in year 1 to 23.8% by year 9, and anti-drug antibodies appeared without neutralising activity or effect on growth.
Four years in Japanese children
In an open-label extension of up to 4 years, height SDS kept rising on weekly somatrogon, including in children switched from daily somatropin; adverse events were mostly mild or moderate and none led to discontinuation.
Real world: weight gain
In treatment-naive children with isolated growth hormone deficiency, height gains on weekly somatrogon matched daily growth hormone, but BMI z-score rose significantly in the first 6 months on somatrogon and stayed higher at 12 months, a finding the authors say needs confirmation.
What reports to regulators show
Across 1,001 FAERS and 863 VigiAccess reports, mostly in children, the recurring signals were injection-site reactions, device problems and IGF-I abnormalities; of 168 FAERS cases with onset data, 79.8% began within 30 days.
Adults with GHD
In 198 treated adults, somatrogon normalised IGF-I but did not reduce trunk fat mass more than placebo at 26 weeks (-0.37 against 0.03 kg, p = 0.08, the primary endpoint); lean body mass improved.
Against matched children on daily GH
The 155 children of the phase 3 somatrogon study were matched with 155 children on daily somatropin in the KIGS registry by region, sex, age, peak GH and height; mean height velocity was similar through years 1 to 3.
Injection pain: switching to somapacitan
Nineteen children who reported injection-site pain on somatrogon switched to somapacitan; pain scores fell from 6.5 to 1.6 on a 10-point scale, and all preferred to stay on somapacitan, in a single-arm study rated after the switch.
Dosing Data
Dosed by label, once weekly on the same day, adjusted to growth response; children switching from daily growth hormone start the next day.
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Side Effects & Contraindications
Reported Side Effects
Warnings from the Ngenla label (version 14).
Contraindications & Cautions
From the label.
Legal Status
Approved in the US for children.
Frequently Asked Questions
?How does it last a week?
Its added hCG-derived peptide tails slow clearance; the label gives an effective half-life of 37.7 hours.
?Is it approved for adults?
Not in the US: the label covers children, and a 2026 adult trial missed its primary endpoint.
?How does it differ from somapacitan?
Both are weekly; somapacitan binds albumin through a fatty side chain, somatrogon carries peptide tails.
?Who is it approved for?
In the US, children 3 and older with growth failure due to inadequate growth hormone secretion.
?Does it work as well as daily injections?
In the pivotal trial, children grew 10.10 cm a year on weekly somatrogon against 9.78 on daily somatropin, meeting non-inferiority.
?What happens over many years?
The phase 2 cohort, followed for nine years, moved from a height SDS of -4.0 to -0.2, with adverse events becoming less frequent over time.
?Can IGF-I go too high?
Yes: in the pivotal extension up to a quarter of children had IGF-I SDS above 2 twice running, meeting the criterion for a dose reduction.
?Does it cause weight gain?
One real-world cohort found BMI z-scores rose faster on somatrogon than on daily growth hormone in the first six months; the authors say this needs confirmation.
?Do injections hurt?
Injection-site pain and redness were the commonest treatment-related effects in the pivotal extension, and children who reported pain had much lower scores after switching to somapacitan in a small study.
References
- [fda-pi] Ngenla (somatrogon-ghla) injection US prescribing information (DailyMed version 14, effective August 14, 2026); read October 1, 2026.
- [pubmed] Deal CL, et al. "Efficacy and Safety of Weekly Somatrogon vs Daily Somatropin in Children With Growth Hormone Deficiency: A Phase 3 Study." J Clin Endocrinol Metab, 2022;107(7):e2717-e2728. PMID: 35405011.
- [pubmed] Zelinska N, et al. "Long-Acting C-Terminal Peptide-Modified hGH (MOD-4023): Results of a Safety and Dose-Finding Study in GHD Children." J Clin Endocrinol Metab, 2017;102(5):1578-1587. PMID: 28323965.
- [pubmed] Fleseriu M, et al. "Efficacy and safety of once-weekly somatrogon in adults with growth hormone deficiency: a randomized phase 3 study." Pituitary, 2026;29(2). PMID: 41879875.
- [pubmed] Horikawa R, et al. "Efficacy and safety of once-weekly somatrogon following up to 4 years of treatment in Japanese children with growth hormone deficiency: results from an open-label extension of a phase 3 study." Endocr J, 2026;73(1):21-32. PMID: 41183961.
- [clinical-trial] Stawerska R, et al. "Extension of the Phase 3 Trial of Somatrogon in Children with Growth Hormone Deficiency: 3 Years of Safety and Efficacy." Horm Res Paediatr, 2026:1-13. PMID: 42224388.
- [clinical-trial] Mauras N, et al. "Open-Label 9-Year Follow-Up Extension Phase 2 Study of Once-Weekly Somatrogon in Children With Growth Hormone Deficiency." J Clin Endocrinol Metab, 2026. PMID: 42372104.
- [pubmed] Moutafi M, et al. "Real world performance of once weekly somatrogon on naive patients with isolated growth hormone deficiency: Mind the weight gain." Growth Horm IGF Res, 2026;85:101714. PMID: 42308661.
- [pubmed] Cai M, et al. "Pharmacovigilance evaluation of somatrogon-associated adverse events in real-world databases." Endocr Connect, 2026;15(6). PMID: 42307062.
- [pubmed] Deal CL, et al. "Weekly somatrogon vs daily somatropin: a propensity score-matched analysis of growth outcomes from clinical data vs KIGS." J Endocr Soc, 2026;10(9):bvag186. PMID: 42662043.
- [pubmed] Iwayama H, et al. "Injection-site pain after switching from somatrogon to somapacitan in children reporting pain or discomfort during once-weekly growth hormone therapy: a prospective single-arm switch study." Front Endocrinol (Lausanne), 2026;17:1849487. PMID: 42741127.
Sources & Citations
Dosing and warnings from the Ngenla label (DailyMed version 14, effective August 14, 2026, read October 1, 2026); approval from Drugs@FDA; studies from PubMed abstracts.
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