Debio 4228

Overview

Debio 4228 is an investigational, long-acting release (LAR) formulation project from Debiopharm intended to improve the convenience of cancer treatments using the company’s DEBIO SPHERE LAR delivery platform. Public materials identify Debio 4228 as a sustained‑release approach rather than a new molecular entity. Debiopharm has not posted human clinical results specific to Debio 4228. In contrast, the active moiety named for this program—degarelix—is a well‑established gonadotropin‑releasing hormone (GnRH) receptor antagonist already approved for advanced prostate cancer and supported by multiple phase II/III trials. Any efficacy and safety results below refer to degarelix as studied/marketed to date, not specifically to the Debio 4228 formulation. Debio 4228‑specific clinical data were not found as of October 7, 2025. (debiopharm.com)

Mechanism of action

Degarelix is a competitive GnRH receptor antagonist that blocks pituitary GnRH receptors, rapidly suppressing luteinizing hormone (LH) and follicle‑stimulating hormone (FSH), which leads to fast and sustained reductions in serum testosterone without the initial testosterone “flare” seen with GnRH agonists. Preclinical and early pharmacology work demonstrated potent, long‑acting suppression of the pituitary–gonadal axis after subcutaneous administration. (pubmed.ncbi.nlm.nih.gov)

Efficacy (degarelix clinical program)

• Phase III, 12‑month randomized trial (CS21, n=610): Degarelix (240 mg loading, then 80 or 160 mg monthly) was non‑inferior to leuprolide (7.5 mg monthly) for maintaining castrate testosterone (≤0.5 ng/mL) from day 28 through 1 year (97.2% and 98.3% with degarelix 240/80 and 240/160 vs 96.4% with leuprolide). Degarelix achieved castrate testosterone by day 3 in ~96% of patients versus none with leuprolide at that time point; PSA declines were faster at days 14 and 28 with degarelix. (bjui-journals.onlinelibrary.wiley.com)

• CS21 secondary analyses and extension:

• Secondary analysis suggested longer time to PSA biochemical recurrence with degarelix versus leuprolide in patients with baseline PSA >20 ng/mL (p=0.04), generating a hypothesis for improved PSA control in higher‑risk subsets. (repub.eur.nl)

• Extension/crossover analyses reported a lower risk of PSA progression‑free survival events with degarelix during year 1 versus leuprolide, with supportive signals after switching from leuprolide to degarelix; these findings are exploratory and need confirmation. (ascopubs.org)

• Phase II (North America, n=127): Rapid and sustained testosterone suppression with monthly maintenance (60 or 80 mg) for 1 year; 88% had testosterone ≤0.5 ng/mL at 1 month; PSA decreased by 96% at 1 year; no testosterone surge observed. (pubmed.ncbi.nlm.nih.gov)

Note: These results describe degarelix as currently used/approved and may not predict performance of any new sustained‑release formulation under the Debio 4228 program.

Safety (degarelix clinical program)

• Common adverse reactions: injection‑site reactions (pain, erythema, swelling), hot flashes, and elevations in transaminases/GGT. Injection‑site reactions occurred far more often with subcutaneous degarelix than with intramuscular leuprolide in CS21 (40% vs <1%). Hypersensitivity reactions (including anaphylaxis/angioedema) have been reported post‑marketing. QT prolongation is a class effect of androgen‑deprivation therapy. (bjui-journals.onlinelibrary.wiley.com)

• Cardiovascular outcomes: Recent meta‑analyses suggest GnRH antagonists such as degarelix are associated with a lower incidence of major adverse cardiovascular events compared with GnRH agonists, though individual endpoints (e.g., MI, stroke) often did not reach significance and heterogeneity exists; further confirmatory studies are needed. (pubmed.ncbi.nlm.nih.gov)

• Hepatic profile: Clinically significant liver injury is uncommon; adverse effects are typically consistent with hypogonadism and injection‑site reactions. (ncbi.nlm.nih.gov)

Safety statements above are based on the marketed degarelix product labeling and clinical experience; Debio 4228‑specific safety has not been reported publicly. (medinfo.ferringconnect.us)

Dosing context for currently approved degarelix (not Debio 4228)

Approved regimens for advanced prostate cancer use a 240 mg loading dose (two 120 mg injections), then 80 mg every 28 days subcutaneously. These details are provided for context on the active moiety and do not describe Debio 4228. (drugs.com)

Further reading

• Debiopharm pipeline description of Debio 4228 (formulation program). (debiopharm.com)
• Phase III CS21 primary results (degarelix vs leuprolide). (bjui-journals.onlinelibrary.wiley.com)
• Secondary analysis of biochemical recurrence (CS21). (repub.eur.nl)
• Long‑term/extension and conference reports on PSA progression‑free survival. (ascopubs.org)
• Phase II dose‑finding (1‑year, North America). (pubmed.ncbi.nlm.nih.gov)
• Cardiovascular risk meta‑analyses contrasting antagonists vs agonists. (pubmed.ncbi.nlm.nih.gov)
• Pharmacology and preclinical profile of degarelix. (pubmed.ncbi.nlm.nih.gov)
• FDA‑aligned safety/dosing information for the marketed degarelix product. (medinfo.ferringconnect.us)

If Debio 4228 clinical trial readouts are released in the future, efficacy and safety sections should be updated to reflect formulation‑specific results.

Last updated: Oct 2025