FDA Approved Growth Hormone Axis

Pegvisomant

also known as: Somavert, B2036-PEG

Pfizer's GH receptor antagonist (Somavert) — FDA-approved in 2003 for acromegaly; important to distinguish from GH agonists because it does the opposite (blocks GH action rather than supplementing it).

A PEGylated recombinant growth hormone analog engineered to bind the GH receptor's primary binding site with higher affinity than native GH while carrying amino acid substitutions at the secondary binding site that prevent functional receptor dimerization — making it a competitive GH receptor antagonist. FDA-approved as Somavert in 2003 for acromegaly in patients who have had inadequate response to surgery, radiation, or somatostatin analogs. Important to distinguish from GH agonists because it *suppresses* GH action and lowers IGF-1; confusing it with a GH-enhancing product is a common internet search error.

Mechanism of action

Competitive antagonism at the GH receptor. Native GH binds its receptor at two sites (binding site 1 with high affinity, binding site 2 with lower affinity) and the second interaction drives receptor dimerization and JAK2/STAT5 signaling. Pegvisomant carries a G120K substitution (and several other changes) that abolish binding site 2 while leaving binding site 1 intact — the drug therefore occupies the receptor and prevents productive dimerization by native GH, lowering IGF-1 generation. PEGylation extends half-life and reduces immunogenicity. Serum IGF-1 is the primary pharmacodynamic marker for titration.

Primary uses

Acromegaly (second- or third-line after surgery, radiation, or somatostatin analogs)

Typical dosing

10–40 mg/day once daily (subcutaneous)

Loading dose of 40 mg on day 1, then 10 mg/day titrated every 4–6 weeks based on serum IGF-1 to the middle of the age-adjusted normal range. Maximum 30 mg/day in the label, though higher doses have been used in practice for incomplete responders.

Regulatory status

FDA-approved March 2003 as Somavert (Pfizer) for the treatment of acromegaly in patients who have had inadequate response to surgery and/or radiation therapy and/or other medical therapies, or for whom these therapies are not appropriate. EMA approval 2002.

References

[fda-pi] Somavert (pegvisomant) Prescribing Information. Pfizer.
[pubmed] Trainer PJ, et al. "Treatment of Acromegaly with the Growth Hormone–Receptor Antagonist Pegvisomant." N Engl J Med, 2000;342:1171-1177.
[review] van der Lely AJ, et al. "Long-term safety of pegvisomant in patients with acromegaly: comprehensive review of 1288 subjects in ACROSTUDY." J Clin Endocrinol Metab, 2012;97:1589-1597.

Related peptides

Somatropin (HGH)

FDA-approved recombinant human growth hormone — the direct hormone replacement, with multiple clinical indications, prescription-only status, and specific federal criminal provisions against off-label distribution.

Lanreotide

The second-generation somatostatin analog (FDA-approved as Somatuline Depot, 2007 for acromegaly; 2014 for GEP-NETs; 2017 for carcinoid) — monthly deep-SC prefilled syringe. Functionally equivalent to octreotide LAR for most indications.

Octreotide

The first-generation somatostatin analog (FDA-approved as Sandostatin, 1988) — the pharmacological counterweight to growth-hormone excess. Used for acromegaly, carcinoid syndrome, and VIPoma; now available in injectable, LAR-depot, and oral (Mycapssa, 2020) formulations.

Disclaimer

This entry is for educational purposes only and does not constitute medical advice. Dosing information reflects published regulatory or research data and is not a recommendation. Many compounds described here are not approved for human use in the United States. Consult a licensed medical professional before considering any peptide therapy.