Somapacitan
Somapacitan, a peptide. A 191-amino-acid human growth hormone analogue carrying a single substitution to which an albumin-binding… Subcutaneous half-life 2 d.
A 191-amino-acid human growth hormone analogue carrying a single substitution to which an albumin-binding fatty-acid side chain is attached; reversible non-covalent binding to circulating albumin is what stretches the dosing interval to weekly. Sogroya label verbatim: "The reversible binding to endogenous albumin delays elimination of somapacitan and thereby prolongs the in vivo half-life and duration of action." Downstream it signals through the growth hormone receptor to drive hepatic IGF-1. NO RECEPTOR AFFINITY IS AUTHORED: PMID:32053994 is the right paper and somapacitan is its subject, but its binding result is qualitative — "Receptor binding isotherms were characterized by a high and a low affinity interaction site with or without HSA" — with no Kd, which is the ixekizumab defect shape R2 names.
THE ITC CONSTANTS ARE RETRIEVED AND DELIBERATELY NOT STORED. Full text PMC7072805 (PMID:32053994) verbatim: "binding between somapacitan and GHBP in the absence of albumin could be characterized by two sets of binding sites with a KD1 of 9.1 nM (high affinity binding site) and a KD2 of 103.9 nM (low affinity binding site)". IN THE ABSENCE OF ALBUMIN IS THE PROBLEM, and it is fatal for this compound specifically: somapacitan is an ALBUMIN-BINDING GH derivative, so the albumin-free affinity is not the affinity anything in plasma has. The same paper says albumin-bound somapacitan binds the receptor with about FIVEFOLD LOWER affinity. Two sites also cannot be one ec50. Storing 9.1 nM would overstate potency at the one condition that never obtains in a patient. THE MASS COMES FROM THE LABEL BECAUSE PUBCHEM IS WRONG FOR THIS DRUG. A PubChem name lookup for `somapacitan` returns CID 129894493, C54H95N13O20S2, 1310.5 (re-queried 2026-09-26) — a 191-residue protein conjugate cannot weigh 1310 Da, and that entry is the albumin-binding side-chain/linker fragment, not the molecule. Storing it would be a silent ~18-fold molar error, the lithium defect shape in R10. The label states the real mass verbatim: "The molecular formula (including the albumin-binding moiety) is C 1038 H 1609 N 273 O 319 S 9 and the molecular weight is 23305.10 g/mol, of which the albumin-binding moiety is 1191.39 g/mol." No salt form; the label adds only that "Hydrochloric acid and sodium hydroxide may be added to adjust the pH." DOSES, label verbatim: "Initiate SOGROYA with a dosage of 1.5 mg once weekly for treatment naive patients and patients switching from daily growth hormone", titrated "every 2 to 4 weeks by approximately 0.5 mg to 1.5 mg", and "The maximum recommended dosage for adult GHD is 8 mg once weekly." Paediatric dosing is weight-based (0.16 mg/kg/week for GHD, 0.24 for SGA, NS and ISS) and is not represented in a fixed-mg row. WHY NO VOLUME WAS DERIVED FROM A Cmax, since single-dose Cmax figures do exist: PMID:28656605 reports "maximum concentration ranged from 21.8 ng/mL (0.02 mg/kg dose) to 458.4 ng/mL (0.16 mg/kg dose)" in children, genuinely single-dose, and the R9 accumulation trap does NOT apply here — the label says steady state arrives in 1 to 2 weeks and PMID:29671202 reports "little or no accumulation of somapacitan". The blocker is R15 instead: an eightfold dose gives a twentyfold Cmax, and the label confirms "a non-linear dose-exposure relationship with a greater than dose proportional increase in exposure", so dose/Cmax is not a volume anyone measured. ANALYTE CAUTION for any future exposure number from PMID:34601071: that study's PK is total somapacitan-related radioactivity, and it states "The total exposure of intact somapacitan accounted for 59% of the total exposure of all somapacitan-related material".
Pharmacokinetics
- Subcutaneous — t½ 2.0 d · F 100% · Vd 14.6 L
Sources: PMID:28656605, PMID:29671202, PMID:32053994, PMID:34601071