Somapacitan

At a glance

Category

Growth hormone

Status

approved drug

Made from

recombinant Produced in Escherichia coli by recombinant DNA technology, then chemically modified with the albumin-binding side chain 1.

Route

subcutaneous injection once weekly, into the upper arm, thigh, abdomen or buttock, rotating the site each week

Half-life

approximately 2 to 3 days in adults with growth hormone deficiency; about 34 hours in children with GHD at 0.16 mg/kg per week and 36-37 hours in children treated at 0.24 mg/kg per week. Reversible binding to endogenous albumin is what delays elimination and prolongs the duration of action 1

Onset

peak somapacitan concentration 4-24 hours after a dose in adults and 8-25 hours in children; steady state is reached after 1 to 2 weekly doses, and IGF-1 peaks 2 to 4 days after dosing 1

Molecular weight

23,305.10 g/mol including the albumin-binding moiety, of which the moiety itself accounts for 1,191.39 g/mol 1

Sequence

The 191-amino-acid human growth hormone sequence with a single L101C substitution, to which an albumin-binding side chain (an albumin binder plus a hydrophilic spacer) is attached at position 101

Mechanism of action

Somapacitan is human growth hormone with one amino acid changed and a small albumin-binding side chain bolted on. It binds the dimeric growth hormone receptor and triggers the same intracellular signalling as somatropin, producing effects that are partly direct and partly mediated by hepatic IGF-1 1. The pharmacology at the receptor is therefore ordinary growth hormone pharmacology; what has been engineered is how long the molecule survives in the circulation.

The half-life extension works by borrowing albumin's own longevity. The side chain binds reversibly and non-covalently to circulating albumin, so the drug is more than 99% protein-bound and is shielded from the renal filtration and proteolysis that clear a 22 kDa protein within hours 1. Because the binding is reversible, a small free fraction remains available to engage the GH receptor at any moment. Elimination proceeds through proteolytic cleavage of the linker between the peptide backbone and the albumin-binding side chain; roughly 81% of the dose leaves in urine and 13% in faeces, and no intact somapacitan is excreted 1.

This is one of three distinct solutions to the same problem, and the three are worth comparing directly. Somapacitan tethers the hormone to albumin. Lonapegsomatropin is a prodrug in which unmodified growth hormone is attached to a large PEG carrier by a linker that cleaves itself at a predictable rate, so the molecule that reaches the receptor is plain somatropin. Somatrogon is a fusion protein carrying three copies of the C-terminal peptide of the beta chain of human chorionic gonadotropin, a heavily glycosylated tail that hCG itself uses to outlast luteinising hormone. All three convert a daily injection into a weekly one; they differ in whether the circulating drug is the hormone itself, and in what else the patient is exposed to.

None of them restores physiological growth hormone secretion. Endogenous GH is pulsatile, with the largest pulses in slow-wave sleep. Daily somatropin already flattens that pattern; a weekly product replaces it with a single long peak and trough per week, with IGF-1 rising to a maximum 2 to 4 days after the dose and falling thereafter 1. The clinical trials measured growth and body composition, not the physiology of the exposure profile, so the long-term consequences of the weekly pattern are an open question rather than a settled one.

What the research shows

The registration evidence is good by the standards of the field: randomised, active-controlled phase 3 trials against daily somatropin in children and a placebo- and active-controlled trial in adults, with regulatory review in both the US and the EU. What the trials show is non-inferiority on surrogate endpoints over one year, not superiority, and not long-term outcomes. There is no fracture-style hard endpoint here, and no head-to-head comparison against the other two weekly products.

Research in humans

In the pivotal paediatric trial (NCT03811535, 200 treatment-naive children with GHD), once-weekly somapacitan 0.16 mg/kg produced an annualised height velocity of 11.2 cm/year at week 52 against 11.7 cm/year for daily somatropin, a treatment difference of -0.5 cm/year with a 95% confidence interval of -1.1 to 0.2 1; this is the REAL4 trial 4. A phase 3 basket study (NCT05330325) supported the higher 0.24 mg/kg per week dose in children born small for gestational age, with Noonan syndrome and with idiopathic short stature 1. In adults, a 35-week double-blind trial (NCT02229851) randomised treatment-naive patients to weekly somapacitan, weekly placebo or daily somatropin; truncal fat fell 1.06% on somapacitan against a 0.47% rise on placebo, a difference of -1.53% (95% CI -2.68 to -0.38, p=0.0090), while daily somatropin gave -2.23% in a comparison that was never formally tested 1. That is the REAL 1 trial 3.

Animal and lab research

Somapacitan was developed from a molecule whose target biology has been characterised in animals for decades, so the preclinical programme addressed the modification rather than the hormone. No long-term carcinogenicity study specific to somapacitan is described in the US label; the neoplasm warnings on the label are inherited from the somatropin class, in particular the increased risk of a second neoplasm in childhood cancer survivors treated with growth hormone and radiation to the head 1.

What it is used for

• Growth failure in children from 2.5 years of age (US) or 3 years (EU) due to inadequate secretion of endogenous growth hormone 12
• Short stature in children born small for gestational age with no catch-up growth by 2 years, growth failure associated with Noonan syndrome, and idiopathic short stature — all on the US label at the higher 0.24 mg/kg weekly dose 1
• Replacement of endogenous growth hormone in adults with growth hormone deficiency 12
• Non-medical use for body composition or athletic performance is not a licensed use, is not supported by any trial, and is explicitly prohibited in sport: somapacitan is named by name on the WADA Prohibited List 5

Dosing

• These are figures from the FDA-approved product information 1, for diagnosed growth hormone deficiency under specialist supervision. They are not a protocol and not advice.
• Adult dosing is titrated on clinical response and serum IGF-1, with the IGF-1 sample drawn 3 to 4 days after the previous dose — the timing matters because concentrations vary substantially across the week 1. The dose is increased by roughly 0.5 to 1.5 mg every 2 to 4 weeks, and reduced for adverse reactions or for IGF-1 above the age- and sex-specific normal range 1.
• Starting doses differ by group: 1 mg weekly in patients aged 65 and over, 2 mg weekly in women taking oral oestrogen (who have lower exposure at the same dose), and 1 mg weekly with a 4 mg maximum in adults with moderate hepatic impairment. Somapacitan is not recommended in severe hepatic impairment, or in children with moderate or severe hepatic impairment 1.
• A missed dose can be taken within 3 days of the scheduled day; beyond that the dose is skipped and the schedule resumed 1.
• The weekly milligram-per-kilogram figures are not comparable between the long-acting products. Somapacitan is dosed at 0.16 mg/kg per week in paediatric GHD, lonapegsomatropin at 0.24 mg/kg per week expressed in somatropin equivalents, and somatrogon at 0.66 mg/kg per week of a 40 kDa fusion protein. The numbers describe different molecules and cannot be converted into one another.
• Somapacitan is dosed in milligrams, not International Units. Grey-market growth hormone figures circulate in IU and do not transfer to this product.

Protocols

Schedules are reproduced as their source states them. Units, IU and milligrams explains why the figures are not interchangeable between products.

Reconstitution

Vial sizes

5 mg/1.5 ml (3.3 mg/ml) single-patient-use prefilled pen, 10 mg/1.5 ml (6.7 mg/ml) single-patient-use prefilled pen, 15 mg/1.5 ml (10 mg/ml) single-patient-use prefilled pen

Storage

Refrigerated at 2-8 °C in the original carton with the cap on, protected from light, both before and during use. Do not freeze; do not use if frozen. Once in use, the pen may be kept refrigerated for up to 6 weeks. Total time at room temperature (up to 25 °C) is limited to 72 hours regardless of whether the pen has been opened. Discard the pen if it has been kept above 30 °C.

Worked example

Not applicable. Somapacitan is supplied as a ready-to-use solution in a prefilled multidose pen; nothing is reconstituted, diluted or calculated. The dose is dialled on the pen in milligrams, in increments of 0.025 mg, 0.05 mg or 0.1 mg depending on the pen strength.

Safety

Side effects

• In adults, adverse reactions reported in more than 2% of treated patients: back pain, arthralgia, dyspepsia, sleep disorder, dizziness, tonsillitis, peripheral oedema, vomiting, adrenal insufficiency, hypertension, raised creatine phosphokinase, weight increase and anaemia 1
• In children: cough, diarrhoea, ear infection, headache, injection site reaction, nasopharyngitis, pain in extremity, pyrexia, respiratory tract infection and vomiting 1
• Fluid retention, which may be dose-dependent; the label directs reducing the dose as necessary 1
• Reduced insulin sensitivity, particularly at higher doses, so glucose is monitored periodically in everyone and more closely in those with or at risk of diabetes 1
• Intracranial hypertension. A fundoscopic examination is required before starting to exclude pre-existing papilloedema, and repeated periodically; if papilloedema occurs on treatment, somapacitan is stopped 1
• Hypoadrenalism may be unmasked or worsened, and patients on glucocorticoid replacement may need higher maintenance or stress doses 1
• Hypothyroidism may become evident or worsen; thyroid function is monitored periodically 1
• Slipped capital femoral epiphysis in children — a limp or persistent hip or knee pain should be evaluated — and progression of pre-existing scoliosis 1
• Pancreatitis, to be considered in anyone with persistent severe abdominal pain 1
• Lipohypertrophy and lipoatrophy where the product is injected repeatedly in the same place; the injection site is rotated weekly for this reason 1
• Serious systemic hypersensitivity reactions including anaphylaxis and angioedema have been reported with somatropin after marketing 1
• Anti-drug antibodies were detected in 12.1% of children with GHD and 14.5% of children born SGA during 52 weeks, in most cases at a single timepoint; none were detected in the adult trials 1

Do not use if

• Acute critical illness following open-heart surgery, abdominal surgery or multiple accidental trauma, or acute respiratory failure, because of the increased mortality reported with pharmacologic doses of growth hormone in this setting 1
• Active malignancy 1
• Hypersensitivity to somapacitan or any excipient 1
• Active proliferative or severe non-proliferative diabetic retinopathy 1
• Closed epiphyses, where the purpose is promoting longitudinal growth in a child 1
• Children with Prader-Willi syndrome who are severely obese, have a history of upper airway obstruction or sleep apnoea, or have severe respiratory impairment, because of reports of sudden death 1
• Not recommended in adults or children with severe hepatic impairment, or in children with moderate hepatic impairment 1

Interactions

Patients on glucocorticoid replacement for hypoadrenalism may need an increase in their maintenance or stress doses once somapacitan is started 1. Somapacitan may alter the clearance of drugs metabolised by cytochrome P450 enzymes, which should be monitored carefully 1. Women taking oral oestrogen have lower somapacitan exposure at the same dose and require larger doses, which is why the label sets a separate 2 mg starting dose for them 1. Insulin and other antihyperglycaemic agents may need dose adjustment because growth hormone decreases insulin sensitivity 1. Somatostatin analogues such as octreotide and lanreotide, and the GH receptor antagonist pegvisomant, act pharmacologically against the same axis.

Sources

• SOGROYA (somapacitan-beco) injection, for subcutaneous use — full prescribing informationDailyMed, Novo Nordisk Inc.
• Sogroya (somapacitan) — EPAR, medicine overview and product informationEuropean Medicines Agency
• Once-weekly Somapacitan is Effective and Well Tolerated in Adults with GH Deficiency: A Randomized Phase 3 TrialJournal of Clinical Endocrinology & Metabolism, 2020
• Weekly Somapacitan is Effective and Well Tolerated in Children With GH Deficiency: The Randomized Phase 3 REAL4 TrialJournal of Clinical Endocrinology & Metabolism, 2022
• The 2026 Prohibited List — World Anti-Doping Code International StandardWorld Anti-Doping Agency
• Drugs@FDA: BLA 761156 (SOGROYA) approval historyUS Food and Drug Administration

Related entries

• SomatropinRecombinant human growth hormone itself: a prescription medicine for growth hormone deficiency.
• SomatrogonWeekly growth hormone fused to three hCG C-terminal peptides, for growth hormone deficiency in children.
• LonapegsomatropinWeekly PEG prodrug of growth hormone: the linker cleaves itself and releases unmodified somatropin.
• hCGPlacental hormone acting on the LH receptor; licensed for fertility, used off-label alongside testosterone.