Degarelix (DB06699): A Comprehensive Monograph on a Third-Generation GnRH Antagonist

I. Executive Summary

Degarelix is a third-generation, synthetic decapeptide gonadotropin-releasing hormone (GnRH) antagonist used as a cornerstone therapy in the management of advanced, hormone-dependent prostate cancer.[1] Classified as a small molecule, its therapeutic effect is derived from a direct and competitive blockade of GnRH receptors located in the pituitary gland.[1] This mechanism of action immediately halts the downstream signaling cascade responsible for the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), leading to a rapid and profound suppression of testicular testosterone production.[1]

A key clinical advantage of Degarelix, which distinguishes it from the more traditional GnRH agonist class of drugs (e.g., leuprolide), is the complete absence of an initial testosterone surge upon administration.[2] This surge, characteristic of agonists, can precipitate a "clinical flare" of symptoms in patients with advanced disease. By avoiding this phenomenon, Degarelix provides a faster and more predictable reduction in both testosterone and prostate-specific antigen (PSA) levels, making it a particularly valuable option for patients requiring urgent disease control.[7]

The safety profile of Degarelix is well-characterized, with the most common adverse events being directly related to its mode of administration and its intended hormonal effects. These include injection site reactions (pain, erythema, swelling), hot flashes, and weight gain.[1] Of significant clinical importance, androgen deprivation therapy as a class, including Degarelix, is associated with a risk of prolonging the QT interval on an electrocardiogram, necessitating caution in patients with pre-existing cardiac conditions or those on concomitant QT-prolonging medications.[2]