Page data last changed: . Chemistry registry snapshot: . Registry refreshes and identity assessments are separate from scientific content review.
A GnRH decapeptide rebuilt with non-natural residues so it blocks the receptor instead of firing it.
Also known as: Firmagon · FE-200486
Part of the Foundational & therapeutic peptides cluster
Overview
Degarelix (Firmagon) is a synthetic decapeptide GnRH receptor antagonist approved by the FDA in 2008 for advanced prostate cancer. By blocking the pituitary receptor directly it lowers LH, FSH and testosterone within days without the testosterone flare of GnRH agonists: 96% of patients reached castrate testosterone by day 3 in the pivotal trial (Klotz et al., BJU International 2008). Its cardiovascular-safety advantage over leuprolide was not confirmed in the PRONOUNCE trial.
Source & context
Biological / chemical source: Synthetic decapeptide derivative of GnRH
Primary research or clinical context: Approved (FDA, 2008) for advanced hormone-dependent prostate cancer; a GnRH receptor antagonist given as a subcutaneous depot
What degarelix is
Degarelix is a synthetic analogue of the GnRH decapeptide with antagonistic action (IUPHAR ligand 5585). It was developed by Ferring under the code FE-200486 and approved by the FDA in 2008 for advanced prostate cancer (Secin, Urologic Oncology 2016). Several positions carry D-amino acids and non-natural side chains — the one-letter backbone AFASXXLKPA marks two as non-canonical — which resist enzymatic breakdown and let the drug form a slow-release depot under the skin. It is marketed as Firmagon.
Mechanism: antagonist, not agonist
GnRH agonists such as leuprolide suppress testosterone by over-stimulating and then desensitising the pituitary receptor, which causes an initial surge in LH and testosterone — the “flare” — before levels fall. Degarelix is a pituitary GnRH receptor antagonist: it blocks the receptor competitively, so gonadotropin release drops at once and testosterone follows within days with no surge (IUPHAR record; Steinberg, Clinical Therapeutics 2009). Animal studies showed the antagonism in the pituitary directly (Steinberg, 2009). The absence of flare is the pharmacological reason to choose an antagonist in men whose disease could worsen with a transient rise in testosterone.
Pivotal trial: CS21
The 12-month phase 3 trial randomised 610 men with prostate adenocarcinoma of any stage (median age 72, median testosterone 3.93 ng/mL, median PSA 19.0 ng/mL) to degarelix 240 mg subcutaneous starting dose followed by monthly 80 mg or 160 mg, or to intramuscular leuprolide 7.5 mg monthly. The primary endpoint, testosterone at or below 0.5 ng/mL at every monthly measurement from day 28 to day 364, was met by 97.2% (240/80 mg), 98.3% (240/160 mg) and 96.4% (leuprolide). By day 3, testosterone was at or below 0.5 ng/mL in 96.1% and 95.5% of the two degarelix groups (Klotz et al., BJU International 2008), demonstrating the rapid, flare-free suppression the antagonist was designed for.
| Arm | Testosterone ≤0.5 ng/mL at all monthly visits | Castrate by day 3 |
|---|---|---|
| Degarelix 240 mg → 80 mg monthly | 97.2% | 96.1% |
| Degarelix 240 mg → 160 mg monthly | 98.3% | 95.5% |
| Leuprolide 7.5 mg monthly | 96.4% | — (agonist flare) |
Cardiovascular safety: the PRONOUNCE result
Whether GnRH antagonists are safer for the heart than agonists was tested directly in PRONOUNCE, an international randomised open-label trial in men with prostate cancer and existing atherosclerotic cardiovascular disease. Enrolment stopped early at 545 of 900 planned patients because of slow accrual and fewer events than projected. Over 12 months a major adverse cardiovascular event occurred in 15 patients (5.5%) on degarelix and 11 (4.1%) on leuprolide — hazard ratio 1.28, 95% CI 0.59–2.79, P = 0.53 (Lopes et al., Circulation 2021). The trial was underpowered, but it did not show the cardiovascular advantage that earlier post-hoc analyses had suggested.
Oncological benefit and its critics
A 2016 critical review argued that the studies published after approval suffered from selection bias, heterogeneous populations, ad-hoc analyses of low statistical merit and selective presentation, and that none had shown an association with clinical benefit beyond testosterone suppression itself (Secin, Urologic Oncology 2016). Comparisons of agonists and antagonists on oncological outcomes reach similar conclusions (Salciccia et al., Urologia 2016). More recently, the randomised phase 2 ARNEO trial found that neoadjuvant degarelix plus apalutamide before radical prostatectomy improved pathological response compared with degarelix alone in high-risk disease, a hypothesis-generating result for phase 3 (Devos et al., European Urology 2023).
Pharmacokinetics and side effects
Degarelix is given as a subcutaneous depot — a 240 mg loading dose then monthly maintenance in the pivotal trial — from which the modified peptide is released slowly; that depot behaviour, not a long plasma half-life of the free peptide, sustains suppression between injections. Injection-site reactions are the characteristic adverse effect of the depot; the endocrine effects of castration (hot flushes, weight gain, loss of bone density, metabolic changes) are shared with all androgen-deprivation therapy. Liver-injury monitoring is described in the LiverTox record (2023). Detailed pharmacokinetic values are not stated in the abstracts reviewed.
Regulatory status as of September 2026
Degarelix is an approved prescription medicine in the United States (2008) and Europe for advanced hormone-dependent prostate cancer, with 170 registered studies including current phase 3 hormone-therapy optimisation trials and neoadjuvant combinations. It is a hospital and specialist drug with no grey-market presence.
Degarelix vs leuprolide, triptorelin and the GnRH family
Leuprolide, triptorelin, goserelin and buserelin are GnRH agonists; degarelix, cetrorelix and ganirelix are antagonists, the latter two used in fertility treatment rather than cancer. Degarelix achieves the same depth of testosterone suppression as leuprolide without the flare (Klotz et al., 2008), but the hoped-for cardiovascular advantage was not demonstrated in PRONOUNCE (Lopes et al., 2021), and independent reviewers have questioned whether any oncological benefit beyond suppression has been shown (Secin, 2016). The leuprolide and gonadorelin profiles cover the agonist side and the native hormone.
Sequence
One-letter sequence commonly cited for Degarelix (educational; isoforms and modifications may differ):
AFASXXLKPA
X = non-canonical or modified residue in the IUPHAR record. X marks a non-canonical residue — see the structure block below. (Plotted as alanine on the wheel.)
Residues plotted ~100° apart around an α-helix — clustering of one color reveals an amphipathic face.
Structure & chemistry
Molecular identity & reference confidence
Source-supported reference
Reference values are taken from the cited molecular record or curated profile. A database match is not independent laboratory verification; modifications, counter-ions, and formulations can change the measured mass.
- Molecular form
- Decapeptide analogue of GnRH; IUPHAR one-letter backbone AFASXXLKPA, where X marks non-canonical residues and several positions carry D-amino acids and modified side chains that resist enzymatic breakdown and form a subcutaneous depot
- Species
- Not established by this molecular identity audit
- Termini (N / C)
- Not specified / Not specified
Average reference mass
Reference policy updated: 2026-10-05
- IUPHAR/BPS source snapshot · 2026-10-01
- PubChem molecular record · 2026-10-01
- Molecular formula
- C82H103ClN18O16
- Average reference mass
- ≈ 1,632.3
- Receptors
- Pituitary gonadotropin-releasing hormone (GnRH) receptor — competitive antagonist; reduces LH and FSH release and therefore testosterone (IUPHAR record)
- Backbone
- Decapeptide analogue of GnRH; IUPHAR one-letter backbone AFASXXLKPA, where X marks non-canonical residues and several positions carry D-amino acids and modified side chains that resist enzymatic breakdown and form a subcutaneous depot
- Status
- Approved (FDA 2008; also EU) for advanced hormone-dependent prostate cancer (IUPHAR record; Secin, 2016)
- PubChem CID: 16136245
- IUPHAR ligand: 5585
- ChEMBL: CHEMBL415606
- DrugBank: DB06699
- CAS RN: 214766-78-6
- UNII: SX0XJI3A11
Chemistry values: curated profile, IUPHAR/BPS Guide to Pharmacology, PubChem · fetched 2026-10-01.
Clinical development snapshot
ClinicalTrials.gov lists 170 registered studies with “Degarelix” as an intervention (snapshot 2026-10-01). A registry footprint is not evidence of efficacy or approval.
| NCT | Title | Phase | Status | Updated |
|---|---|---|---|---|
| NCT01630967 | Efficacy Study of Switching to a Lutenizing Hormone-releasing Hormone (LHRH) Antagonist From a LHRH Agonist to | Phase 2 | withdrawn | 2026-10-01 |
| NCT04989946 | Androgen Deprivation, With or Without pTVG-AR, and With or Without T-Cell Checkpoint Blockade, in Patients Wit | Phase 2 | active not recruiting | 2026-09-30 |
| NCT05241860 | Testing Interruption of Hormonal Medications in Patients Responding Exceptionally to Therapy for Metastatic Pr | Phase 2 | active not recruiting | 2026-09-24 |
| NCT06379217 | NEPC Study: An Exploratory Safety and Efficacy Study With PSMA, SSTR2 and GRPR Targeted Radioligand Therapy in | Phase 1 | active not recruiting | 2026-09-22 |
| NCT03070886 | Antiandrogen Therapy and Radiation Therapy With or Without Docetaxel in Treating Patients With Prostate Cancer | Phase 3 | active not recruiting | 2026-09-14 |
| NCT07335796 | A Study of BMS986365 in Combination With Degarelix in People With Prostate Cancer | Phase 2 | active not recruiting | 2026-09-11 |
Degarelix — reconstitution calculator
Enter how much peptide is in the vial and how much diluent (e.g. bacteriostatic water) is added. The tool returns the resulting solution concentration — and, for any amount you type, the volume it corresponds to. This is educational arithmetic, not a dosing recommendation.
Reference form: Decapeptide analogue of GnRH; IUPHAR one-letter backbone AFASXXLKPA, where X marks non-canonical residues and several positions carry D-amino acids and modified side chains that resist enzymatic breakdown and form a subcutaneous depotAverage reference mass: 1,632.3 Da
Enter an amount to see the volume it corresponds to.
Educational concentration mathematics only. This tool does not recommend a dose, amount, or protocol, and nothing here is medical advice. Many peptides are not authorized by Health Canada for human use — see our reconstitution and bacteriostatic-water guides for context.
Change log
Dated observations from the data pipeline (registry flags, trial footprints, identifiers) and editorial reviews of this profile.
- EditorialProfile content reviewed and updated by the editorial team.
FAQ about Degarelix
What is Degarelix?+
Degarelix (Firmagon) is a synthetic decapeptide GnRH receptor antagonist approved by the FDA in 2008 for advanced prostate cancer. By blocking the pituitary receptor directly it lowers LH, FSH and testosterone within days without the testosterone flare of GnRH agonists: 96% of patients reached castrate testosterone by day 3 in the pivotal trial (Klotz et al., BJU International 2008). Its cardiovascular-safety advantage over leuprolide was not confirmed in the PRONOUNCE trial.
What Canadian product status is recorded for Degarelix?+
Canadian product status for Degarelix has not been verified in this profile. No verified record here does not mean no authorization exists. Status depends on the product, formulation and use; consult Health Canada's product records.
What is the typical length of Degarelix?+
Degarelix is commonly described as approximately 10 amino acids (GnRH antagonist).
What is degarelix?+
A synthetic decapeptide GnRH receptor antagonist (Firmagon) approved in 2008 for advanced prostate cancer. It lowers testosterone rapidly by blocking the pituitary receptor directly.
How does degarelix differ from leuprolide?+
Leuprolide is an agonist that causes an initial testosterone flare before suppression; degarelix is an antagonist with no flare — 96% of patients were castrate by day 3 in the pivotal trial (Klotz et al., 2008).
Is degarelix safer for the heart than leuprolide?+
PRONOUNCE did not show that: MACE occurred in 5.5% on degarelix and 4.1% on leuprolide over 12 months (HR 1.28, P = 0.53), in an underpowered trial (Lopes et al., 2021).
What is degarelix's mechanism of action?+
Competitive antagonism of the pituitary GnRH receptor, reducing LH and FSH release and therefore testicular testosterone production.
What are degarelix's side effects?+
Injection-site reactions from the depot, plus the effects of androgen deprivation shared with all such therapy (hot flushes, weight gain, bone loss).
Is degarelix approved?+
Yes — FDA 2008 and in Europe, for advanced hormone-dependent prostate cancer.
Further reading
- PK conceptsWhy Peptides Have Short Half-Lives (And How Engineers Fix It)Proteases, renal clearance, DPP-4, PEGylation, lipidation, cyclization—educational guide to peptide pharmacokinetics concepts.
- ManufacturingPeptide Synthesis Basics for Non-ChemistsPlain-language introduction to solid-phase peptide synthesis (SPPS), purification, and why custom peptides cost what they cost.
- SafetyPeptide Safety and Risks: A Balanced Educational OverviewAn objective, balanced overview of what research does and does not establish about peptide risks—unknowns, purity and contamination concerns, and why unapproved compounds carry uncertainty. Not reassurance and not medical advice.
Related peptides
References & further reading
- 1.Devos et al. (2023). ARNEO: A Randomized Phase II Trial of Neoadjuvant Degarelix with or Without Apalutamide Prior to Radical Prostatectomy for High-risk Prostate Cancer. Eur Urol
- 2.Klotz et al. (2008). The efficacy and safety of degarelix: a 12-month, comparative, randomized, open-label, parallel-group phase III study in patients with prostate cancer. BJU Int
- 3.Lopes et al. (2021). Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Prostate Cancer: The Primary Results of the PRONOUNCE Randomized Trial. Circulation
- 4.Frampton et al. (2009). Degarelix. Drugs
- 5.Clinton et al. (2017). Degarelix versus luteinizing hormone-releasing hormone agonists for the treatment of prostate cancer. Expert Opin Pharmacother
- 6.Ferrazzano et al. (2023). Investigation of the GnRH antagonist degarelix isomerization in biological matrices. Pharmacol Res Perspect
- 7.Carter et al. (2014). Degarelix: a review of its use in patients with prostate cancer. Drugs
- 8.Giesen et al. (2026). Final Results of the Randomised Phase 2 Trial of Neoadjuvant Degarelix with or Without Apalutamide Prior to Radical Prostatectomy for High-risk Prostate Cancer (ARNEO). Eur Urol Oncol
- 9.Secin (2016). Questionable oncologic benefits of degarelix. Urologic Oncology
- 10.Steinberg (2009). Degarelix: a gonadotropin-releasing hormone antagonist for the management of prostate cancer. Clinical Therapeutics
- 11.Salciccia et al. (2016). GnRH-agonist or antagonist in the treatment of prostate cancer: a comparison based on oncological results. Urologia
- 12.PubChem — Degarelix, CID 16136245