Approved & therapeutic
Pegvisomant
Somavert
Pegvisomant is a pegylated growth hormone receptor antagonist approved in the US for acromegaly in patients who have had an inadequate response to surgery or radiation therapy, or for whom those therapies are not appropriate. It lowers insulin-like growth factor 1 while serum growth hormone actually rises during treatment. It is a licensed biologic supplied as a lyophilised powder for subcutaneous injection.
- Status
- Pegvisomant is approved by the U.S. FDA and has official prescribing information.
- Evidence
- Approved labeling. Official prescribing information exists, based on clinical trials in people.
- Half-life
- Approximately 60 to 138 hours (mean estimates) following either single or multiple doses, per human pharmacokinetics in label section 12.3.
- How it's taken
- Subcutaneous injection
- Mechanism
- Other
- Pathways
- GH axis
How Pegvisomant works
Pegvisomant is a modified growth hormone analog that binds selectively to growth hormone receptors on the cell surface and blocks the binding of endogenous growth hormone, preventing functional receptor dimerisation and interfering with growth hormone signal transduction. The result is reduced hepatic production of insulin-like growth factor 1. Because it acts at the receptor rather than on the pituitary, the adenoma itself is not treated, and serum growth hormone concentrations rise rather than fall: measured with research assays that do not cross-react with pegvisomant, growth hormone increased within two weeks of starting treatment, presumably from diminished IGF-1 negative feedback.
What research has looked at
- In the 12-week randomised, double-blind, placebo-controlled registration trial (112 patients), the primary efficacy endpoint was percent change in serum IGF-1 from baseline to week 12. IGF-1 fell by 27, 48 and 63 percent across the three ascending dose groups versus 4 percent with placebo (p<0.01 for each comparison).
- Normalisation of serum IGF-1 at week 12 was a secondary result and increased with dose; normalising IGF-1 is the treatment goal stated in the labeled indication. In the open-label extension, 100 of 108 patients with available data (92.6 percent) had a normal IGF-1 at some visit.
- Secondary endpoints in the same trial showed statistically significant improvement versus placebo only at the two higher doses studied, and only for ring size, soft-tissue swelling, excessive perspiration and fatigue. Arthralgia and headache changed minimally and were not significantly improved; the label reports these signs and symptoms without p-values.
- Provides a labeled option for patients whose acromegaly has responded inadequately to surgery or radiation therapy, or for whom those therapies are not appropriate. Use after failure of somatostatin analog therapy is common in clinical practice but is not part of the US labeled indication.
Evidence level: Approved labeling. Official prescribing information exists, based on clinical trials in people. These are areas studied or reported, not promised effects.
Reported side effects and risks
- Liver toxicity: asymptomatic, transient transaminase elevations up to 15 times the upper limit of normal were seen in under 2 percent of 147 subjects across two open-label trials, and ALT or AST above 10 times the upper limit of normal occurred in 2 patients (0.8 percent) in pre-approval studies. Postmarketing reports describe hepatic transaminases above 20 times the upper limit of normal with total bilirubin above twice the upper limit. Liver tests are required before starting and periodically during treatment.
- Hypoglycemia in patients with diabetes mellitus: growth hormone opposes insulin's effect on carbohydrate metabolism, so glucose tolerance may improve and doses of anti-diabetic drugs, including insulin and oral hypoglycemic agents, may need to be reduced to avoid hypoglycemia.
- Cross-reactivity with commercial growth hormone assays: pegvisomant is structurally similar to growth hormone and makes serum growth hormone measurements appear falsely elevated, so growth hormone is unusable for monitoring. Treatment is titrated on serum IGF-1 only.
- Lipohypertrophy at injection sites; injection sites should be rotated.
- Systemic hypersensitivity reactions, including reports on re-initiation of therapy after an interruption.
- Opioid interaction: in clinical studies, patients taking opioids often required higher pegvisomant doses than patients not on opioids to normalise IGF-1.
- Because the drug does not lower growth hormone secretion or shrink the pituitary adenoma, tumour size requires ongoing imaging surveillance. In postmarketing registry MRI data on 1,795 patients, 7.1 percent had an increase in lesion size, 17.3 percent a decrease, 4.5 percent both, and 71.1 percent no change.
- Common adverse reactions reported in more than 6 percent of patients in trials: infection, pain, nausea, diarrhea, abnormal liver tests, flu syndrome and injection site reactions. There is no boxed warning and the label's Contraindications section reads None; safety and effectiveness in pediatric patients have not been established.
Sources
- PubMed research on Pegvisomant · NIH · National Library of Medicine
- DrugBank record for Pegvisomant · DrugBank
- Active clinical trials for Pegvisomant · U.S. National Library of Medicine
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Pegvisomant FAQ
What is Pegvisomant?
Pegvisomant is a pegylated growth hormone receptor antagonist approved in the US for acromegaly in patients who have had an inadequate response to surgery or radiation therapy, or for whom those therapies are not appropriate. It lowers insulin-like growth factor 1 while serum growth hormone actually rises during treatment. It is a licensed biologic supplied as a lyophilised powder for subcutaneous injection.
How does Pegvisomant work?
Pegvisomant is a modified growth hormone analog that binds selectively to growth hormone receptors on the cell surface and blocks the binding of endogenous growth hormone, preventing functional receptor dimerisation and interfering with growth hormone signal transduction. The result is reduced hepatic production of insulin-like growth factor 1. Because it acts at the receptor rather than on the pituitary, the adenoma itself is not treated, and serum growth hormone concentrations rise rather than fall: measured with research assays that do not cross-react with pegvisomant, growth hormone increased within two weeks of starting treatment, presumably from diminished IGF-1 negative feedback.
Is Pegvisomant FDA approved?
Yes. Pegvisomant is approved by the U.S. FDA and has official prescribing information. Evidence level: approved labeling. Official prescribing information exists, based on clinical trials in people.
What is the half-life of Pegvisomant?
Reported half-life: Approximately 60 to 138 hours (mean estimates) following either single or multiple doses, per human pharmacokinetics in label section 12.3.
How is Pegvisomant taken?
Subcutaneous injection.
What side effects have been reported with Pegvisomant?
Reported in the sources: Liver toxicity: asymptomatic, transient transaminase elevations up to 15 times the upper limit of normal were seen in under 2 percent of 147 subjects across two open-label trials, and ALT or AST above 10 times the upper limit of normal occurred in 2 patients (0.8 percent) in pre-approval studies. Postmarketing reports describe hepatic transaminases above 20 times the upper limit of normal with total bilirubin above twice the upper limit. Liver tests are required before starting and periodically during treatment; Hypoglycemia in patients with diabetes mellitus: growth hormone opposes insulin's effect on carbohydrate metabolism, so glucose tolerance may improve and doses of anti-diabetic drugs, including insulin and oral hypoglycemic agents, may need to be reduced to avoid hypoglycemia; Cross-reactivity with commercial growth hormone assays: pegvisomant is structurally similar to growth hormone and makes serum growth hormone measurements appear falsely elevated, so growth hormone is unusable for monitoring. Treatment is titrated on serum IGF-1 only; Lipohypertrophy at injection sites; injection sites should be rotated; Systemic hypersensitivity reactions, including reports on re-initiation of therapy after an interruption; Opioid interaction: in clinical studies, patients taking opioids often required higher pegvisomant doses than patients not on opioids to normalise IGF-1; Because the drug does not lower growth hormone secretion or shrink the pituitary adenoma, tumour size requires ongoing imaging surveillance. In postmarketing registry MRI data on 1,795 patients, 7.1 percent had an increase in lesion size, 17.3 percent a decrease, 4.5 percent both, and 71.1 percent no change; Common adverse reactions reported in more than 6 percent of patients in trials: infection, pain, nausea, diarrhea, abnormal liver tests, flu syndrome and injection site reactions. There is no boxed warning and the label's Contraindications section reads None; safety and effectiveness in pediatric patients have not been established.
Educational summary compiled from the sources listed above. Not medical advice. Peptide Vault does not sell, source or recommend any compound. Talk to a qualified clinician before starting or changing anything.