Degarelix

Mechanism

Degarelix is a synthetic linear decapeptide that acts as a competitive antagonist at the gonadotropin-releasing hormone (GnRH) receptor in the anterior pituitary. By binding to and blocking GnRH receptors, it prevents endogenous GnRH from stimulating the release of luteinising hormone (LH) and follicle-stimulating hormone (FSH). The result is an immediate, dose-dependent suppression of gonadotropin secretion, which in turn causes a rapid decrease in testicular testosterone production. Unlike GnRH agonists (which initially overstimulate the receptor before causing downregulation), degarelix does not produce an initial LH/testosterone surge — it blocks from the first dose. Testosterone falls to castration levels (≤0.5 ng/mL) typically within 3 days of the loading dose. The antagonism is reversible, and pituitary-gonadal function recovers after discontinuation.

Evidence base

Pivotal Phase III Trial (CS21)

The CS21 trial randomised 610 patients with prostate cancer to degarelix (240 mg loading, then 80 mg monthly) or leuprolide (7.5 mg monthly). Degarelix achieved non-inferiority for the primary endpoint (testosterone ≤0.5 ng/mL at all monthly measurements from Day 28 to Month 12). Critically, degarelix suppressed testosterone to castrate levels within 3 days in 96% of patients, with no testosterone surge, versus 0% at Day 3 for leuprolide (Klotz et al., BJU Int, 2008).

Long-Term Extension (CS21A)

The 5-year extension confirmed sustained testosterone suppression and PSA control. Subgroup analysis suggested patients with metastatic disease on degarelix had a lower risk of skeletal-related events and longer time to progression compared with leuprolide (Saad et al., 2012).

Cardiovascular Safety

A pooled analysis of five RCTs suggested degarelix was associated with fewer cardiovascular events and cardiovascular deaths compared with GnRH agonists (Albertsen et al., J Urol, 2014). The hypothesis that direct antagonism confers a cardiovascular advantage remains under investigation.

PSA and Alkaline Phosphatase

Degarelix produced more rapid PSA declines and greater reductions in alkaline phosphatase (a marker of bone metastasis activity) compared with leuprolide in the CS21 trial.

Protocols

Loading Dose (Initial)

• 240 mg subcutaneously, administered as two separate 120 mg injections at different sites.

Maintenance Dose

• 80 mg subcutaneously every 28 days (monthly), starting 4 weeks after the loading dose.

Administration Notes

• Inject slowly (the solution is viscous).
• Rotate injection sites.
• Monitor testosterone at Day 3, Month 1, and then every 3 months.

All dosing reflects the licensed UK SmPC. This is a POM; administration occurs under specialist oncology or urology supervision. This profile is for research and educational purposes only.

UK legal status

Degarelix is a prescription-only medicine (POM) in the UK under the Human Medicines Regulations 2012. It is licensed for the treatment of advanced hormone-dependent prostate cancer. The licensed product (Firmagon) holds a UK marketing authorisation regulated by the MHRA. Supply without a valid prescription is unlawful. It is not classified as a controlled substance under the Misuse of Drugs Act 1971.

Vendor notes

As a licensed POM, degarelix is dispensed by hospital pharmacies and specialist oncology services upon prescription. It is not available from research peptide vendors. Peptide Data does not list vendors for this compound.