Pegvisomant

A PEGylated 191-residue analog of human growth hormone that blocks the growth hormone receptor, FDA approved since 2003 as Somavert for acromegaly, lowering IGF-1 rather than growth hormone itself through once-daily subcutaneous injection.

Also referenced as: Somavert, B2036-PEG, B2036

Also appears in: Hormone

COA Public product evidence No certificate records are bound to a tracked Pegvisomant product page A record counts here only when a vendor publishes a certificate against one of its own tracked Pegvisomant product pages. Other certificates naming this compound may still exist — search the wider certificate database. →

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What is Pegvisomant?

Pegvisomant is a recombinant, PEGylated analog of human growth hormone that acts as a growth hormone receptor antagonist. It is a 191-residue protein, the same length as native growth hormone, so it is a protein therapeutic rather than a short peptide. The protein backbone, developed under the code B2036, differs from human growth hormone at nine positions (His18Asp, Ala21Asn, Gly120Lys, Arg167Asn, Lys168Ala, Asp171Ser, Lys172Arg, Glu174Ser, Ile179Thr), is expressed in E. coli with two internal disulfide bonds, and is then covalently modified with polyethylene glycol chains of roughly 5 kDa each. The EU assessment describes four to five PEG groups per molecule as the predominant species; the FDA label puts the 22 kDa protein’s predominant PEGylated molecular weights near 42, 47, and 52 kDa, which correspond to four, five, and six chains.

It reaches the clinic as Somavert, approved by the FDA on March 25, 2003 under application 021106 (filed as an NDA, deemed a BLA in March 2020) for acromegaly in patients who have had an inadequate response to surgery or radiation therapy, or for whom those therapies are not appropriate; the label states the goal of treatment is a normal IGF-1. The EU authorization dates to November 12, 2002, and the product is marketed by Pfizer through its Pharmacia & Upjohn subsidiary. It appears in peptide discussions almost entirely as the pharmacological opposite of the growth hormone secretagogues: where those compounds aim to raise growth hormone and IGF-1, pegvisomant is the one agent built to shut growth hormone signaling off. It is not a feature of the research-vendor market in any meaningful way, and a lyophilized vial labeled “pegvisomant” would have to be a recombinant protein product, not a synthetic peptide.

How it works

Growth hormone signals by binding one receptor molecule at site 1 and then recruiting a second receptor molecule at site 2, and it is the resulting receptor dimer that activates downstream JAK2/STAT5 signaling and hepatic IGF-1 production. Pegvisomant exploits that two-step binding:

• Site 2 blockade via Gly120Lys — substituting lysine for glycine at position 120 sterically disrupts the second receptor contact, so the molecule occupies a receptor without triggering functional dimerization and signaling. The remaining eight substitutions, derived from alanine-scanning work on growth hormone, alter site 1 binding so that the antagonist competes effectively with endogenous hormone for the receptor (Kopchick et al., Endocrine Reviews, 2002, 23(5):623–646)
• PEGylation for half-life, at a cost in affinity — the unmodified B2036 protein is cleared quickly; attaching PEG chains extends the circulating half-life to several days (mean estimates of 60 to 138 hours in the FDA label and 74 to 172 hours in the EU summary of product characteristics), which is what makes once-daily injection workable. PEGylation also reduces receptor binding relative to the unmodified antagonist, so the dose required is higher, but the EU scientific assessment notes that the PEGylated form is more potent overall because of its prolonged circulation (Kopchick et al., Endocrine Reviews, 2002; EMA Somavert scientific discussion)
• Dose-dependent IGF-1 suppression without lowering growth hormone — in the pivotal 12-week trial of 112 patients, serum IGF-1 fell 26.7%, 50.1%, and 62.5% from baseline at 10, 15, and 20 mg daily versus 4.0% on placebo, and IGF-1 normalized in 54%, 81%, and 89% of patients respectively versus 10% on placebo; ring size, soft-tissue swelling, sweating, and fatigue improved at the two higher doses (Trainer et al., New England Journal of Medicine, 2000, 342(16):1171–1177)
• Serum growth hormone rises, not falls — because the pituitary tumor keeps secreting and the IGF-1 feedback loop is interrupted, growth hormone concentrations increase within about two weeks of starting treatment, and pegvisomant itself cross-reacts with commercial growth hormone immunoassays. Efficacy is therefore judged on IGF-1 alone, a point the FDA label makes explicit in directing that dose be titrated to IGF-1 and never to growth hormone concentrations or to signs and symptoms

Research status

Pegvisomant has one of the longest human evidence records of any growth hormone axis drug, concentrated in a single rare disease.

Pivotal and long-term trials. The randomized, double-blind, placebo-controlled trial by Trainer et al. (NEJM, 2000) established dose-dependent IGF-1 normalization over 12 weeks. The open-label follow-on by van der Lely et al. (Lancet, 2001, 358(9295):1754–1759) treated 160 patients for a mean of 425 days: among those treated 12 months or longer, 87 of 90 (97%) achieved a normal IGF-1, anti-growth-hormone antibodies appeared in 16.9% without tachyphylaxis, two patients had progressive tumor growth, and two were withdrawn for elevated aminotransferases. Mean pituitary tumor volume did not change significantly in the 131 patients with serial MRI. The label’s own extension data put 100 of 108 subjects with IGF-1 data (92.6%) at a normal IGF-1 at some visit over a mean exposure of 42.6 weeks.

ACROSTUDY (post-marketing surveillance, 2004–2017). The global registry is the main source of real-world data. The 2012 interim report on 1,288 patients found 63.2% with normal IGF-1 at five years on a mean dose of 18 mg/day, AST or ALT above three times the upper limit of normal in 2.5% with no liver failure, injection-site reactions in 2.2%, and increased tumor size on central MRI reading in 3.2% (van der Lely et al., Journal of Clinical Endocrinology & Metabolism, 2012, 97(5):1589–1597). The 2018 interim analysis of 2,090 patients reported IGF-1 normalization rising from 53% at year one to 73% at year ten as mean dose climbed from 12.8 to 18.9 mg/day, with a tumor-size increase on local MRI reading in 6.8% (Buchfelder et al., European Journal of Endocrinology, 2018, 179(6):419–427). The final analysis of 2,221 patients with a median 9.3 years on drug reported 75.4% IGF-1 normalization at year ten, treatment-related adverse events in 16.5%, discontinuation for them in 1.3%, abnormal AST or ALT in 3.2%, and pituitary tumor enlargement in 7.1% (Fleseriu et al., European Journal of Endocrinology, 2021, 185(4):525–538). A 2026 monotherapy-only analysis of 1,464 patients found 62.3% with normal IGF-1 at last observation on a median 15 mg/day, with lipohypertrophy and transaminase increases each in 1.2%, tumor growth on site MRI in 7.2%, and none of the 31 deaths attributed to treatment (Yuen et al., Pituitary, 2026, 29(3):71).

Combination regimens. Weekly pegvisomant layered onto a monthly long-acting somatostatin analog normalized IGF-1 in 18 of 19 patients who completed a 42-week, 26-patient dose-finding study, but mild liver enzyme elevations occurred in 10 of 26 (38%), a markedly higher rate than monotherapy (Feenstra et al., Lancet, 2005, 365(9471):1644–1646). The liver signal has a pharmacogenetic component: in 36 Spanish patients, carriers of the UGT1A1*28 Gilbert’s syndrome allele had liver test abnormalities at 43% versus 7% in wild-type patients (Bernabeu et al., Journal of Clinical Endocrinology & Metabolism, 2010, 95(5):2147–2154).

Beyond acromegaly. The record outside acromegaly is thin and largely negative or unresolved. A Pfizer Phase 1 trial of pegvisomant with the IGF-1 receptor antibody figitumumab in advanced solid tumors (NCT00976508) was terminated in 2011 after enrolling 24 patients, for slow recruitment and business reasons rather than safety. Small mechanistic studies have used it as a tool to switch off growth hormone action in healthy volunteers, fasting physiology, and prediabetes, none of which produced a therapeutic program. As of November 2026 the only registered activity is at the NIH: an NICHD Phase 3 open-label study in 12 children with growth hormone excess (NCT03882034) completed in September 2025 with no results posted, and an NIDDK Phase 2 study of 30 mg daily in severe insulin resistance from insulin receptor mutations or partial lipodystrophy (NCT05470504) is recruiting toward a 2028 completion. There is no registered program in body composition, anti-aging, or performance contexts.

Regulatory record. The most recent FDA action on application 021106 is an efficacy-labeling supplement with clinical data (S-074) approved July 27, 2023; the current label is dated 7/2023 and was reposted to DailyMed in December 2025. Drugs@FDA lists no submissions in 2024, 2025, or 2026, lists no second application for pegvisomant, and the label states that safety and effectiveness in pediatric patients have not been established. In the EU the product information was last updated in February 2025.

Common dosage forms

• Approved product — lyophilized powder in single-dose vials of 10, 15, 20, 25, and 30 mg, each packaged with a 1 mL prefilled diluent syringe of sterile water and a 27-gauge safety needle, in one-day or 30-day kits. The format is once-daily subcutaneous injection after reconstitution. Vials are stored refrigerated and may be held at room temperature for a single period of up to 30 days.
• No pen or autoinjector — despite how it is sometimes described, the U.S. and EU products are vial-and-syringe kits only; neither the FDA label nor the EU product information lists a pen presentation.
• Research supply — pegvisomant is not a standard offering in the research-peptide channel. Any material sold under the name would need to be a recombinant, PEGylated protein, which is not something a peptide synthesis supply chain produces.

Key considerations

• It is a protein and an antagonist. It is the only approved drug that blocks the growth hormone receptor directly, and its entire approved purpose is to lower IGF-1 in acromegaly. At 191 residues it is a protein, not a short peptide, and it should not be grouped with growth hormone secretagogues like CJC-1295 or ipamorelin, which do the opposite.
• Liver enzyme elevations are the signature safety signal. The label carries a Liver Toxicity warning that calls for baseline and periodic liver tests with discontinuation thresholds; transaminase elevations above three times the upper limit of normal occurred in roughly 2.5% to 3.2% of ACROSTUDY patients, with no liver failure reported. The rate rises sharply when pegvisomant is combined with somatostatin analogs (38% in the Feenstra series) and in carriers of the UGT1A1*28 polymorphism. Elevations have generally been reversible on withdrawal.
• Injection-site lipohypertrophy and tumor surveillance. Lipohypertrophy at injection sites is a labeled warning (1.2% of monotherapy patients in the final ACROSTUDY cohort; one case in the pivotal program) and has been managed by rotating sites. Because the drug does not act on the pituitary tumor, growth hormone output continues and the label’s patient counseling directs that these tumors be watched by MRI; tumor enlargement was reported in 3% to 7% of ACROSTUDY patients, overlapping with the natural history of post-surgical adenomas.
• Growth hormone assays become uninterpretable. Serum growth hormone rises during treatment and pegvisomant cross-reacts with growth hormone immunoassays, so any evaluation that relies on measured growth hormone is unreliable during exposure. The label also warns of hypoglycemia in patients with diabetes as IGF-1 falls, since growth hormone normally opposes insulin.
• No approval outside acromegaly, no established pediatric use, and no biosimilar. The FDA Approved status reflects Somavert’s March 2003 approval for acromegaly. That approval has not been extended to pediatric gigantism, and the completed NICHD study has not reported. Drugs@FDA lists a single application for the molecule, so Somavert remains the only U.S. product. Claims that pegvisomant is useful for fat loss or insulin sensitivity rest on small mechanistic studies and one recruiting NIH trial, not on any outcome data.