Pegvisomant (Somavert®): A Comprehensive Monograph on its Pharmacology, Clinical Efficacy, and Therapeutic Role in Acromegaly

Executive Summary

Pegvisomant represents a first-in-class therapeutic agent for the management of acromegaly, a condition driven by excessive growth hormone (GH). Classified as a biotech drug, Pegvisomant is a pegylated, recombinant protein engineered to function as a highly selective growth hormone receptor (GHR) antagonist.[1] Its therapeutic approach is unique among acromegaly treatments. Instead of inhibiting the secretion of GH from the pituitary gland, Pegvisomant acts peripherally to block the binding of endogenous GH to its receptors on cell surfaces. This targeted antagonism prevents GH signal transduction, leading to a marked reduction in the synthesis and serum levels of Insulin-like Growth Factor-1 (IGF-1), the principal mediator of the pathophysiological effects of acromegaly.[1]

The medication has established efficacy as a second- or third-line therapy for adult patients who have had an inadequate response to surgery, radiation, or treatment with somatostatin analogs, or for whom those therapies are not appropriate.[2] Clinical monitoring and dose titration for Pegvisomant are based exclusively on normalizing serum IGF-1 levels, as circulating GH levels paradoxically rise during treatment and are not a valid measure of efficacy.[4] Key safety considerations necessitate diligent monitoring of liver function due to a risk of transaminase elevation and regular pituitary imaging to assess tumor volume, although the risk of tumor growth is low.[8] Overall, Pegvisomant is a powerful and specialized pharmacotherapy that offers a distinct and highly effective mechanism for controlling the biochemical markers and clinical manifestations of acromegaly.

Molecular Profile and Pharmaceutical Development

Discovery and Development History