Firmagon is a GnRH antagonist and different from previously available GNRH stimulators in that it does not cause an initial stimulation of the hypothalamic-pituitary-gonadal axis (HPGA), leading to a surge in testosterone levels, and under certain circumstances, a flare-up of the tumor.
A Phase III, randomised, 12 month clinical trial (CS21) compared standard androgen deprivation with one of two doses of degarelix or the GnRH agonist, leuprolide. Both degarelix doses were at least as effective as leuprolide at suppressing testosterone to castration levels (≤0.5 ng/mL) from Day 28 to study end (Day 364). Testosterone levels were suppressed significantly faster with degarelix than with leuprolide, with degarelix uniformly achieving castration levels by Day 3 of treatment which was not seen in the leuprolide group. There were no testosterone surges with degarelix compared with surges in 81% of those who received leuprolide. Degarelix resulted in a faster reduction in PSA levels compared with leuprolide indicating faster control of the prostate cancer. Recent results also suggest that degarelix therapy may result in longer control of prostate cancer compared with leuprolide.
On 24 December 2008, the Food and Drug Administration (FDA) approved degarelix for the treatment of patients with advanced prostate cancer in the USA. It was subsequently approved by the European Commission at the recommendation of the European Medicines Agency (EMEA) on February 17, 2009 for use in adult male patients with advanced, hormone-dependent prostate cancer. Ferring Pharmaceuticals markets the drug under the name Firmagon.
Princivalle M, Broqua P, White R, et al (March 2007). Rapid suppression of plasma testosterone levels and tumor growth in the dunning rat model treated with degarelix, a new gonadotropin-releasing hormone antagonist. J. Pharmacol. Exp. Ther. 320: 1113-8.
Van Poppel H, Nilsson S (June 2008). Testosterone surge: rationale for gonadotropin-releasing hormone blockers? Urology 71: 1001-6.
Klotz L, Boccon-Gibod L, Shore ND, et al (December 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. 102: 1531-8.
Schröder FH, Boccon-Gibod L, Tombal B, et al (March 2009) Degarelix versus leuprolide in patients with prostate cancer: effect in metastatic patients as assessed by serum alkaline phosphatase. European Association of Urology (EAU) Annual congress 17–21 March 2009, Stockholm, Sweden. Abstract 40.
Gittelman M, Pommerville PJ, Persson BE, et al (November 2008). A 1-year, open label, randomized phase II dose finding study of degarelix for the treatment of prostate cancer in North America. J. Urol. 180: 1986-92.
Van Poppel H, Tombal B, de la Rosette JJ, et al (October 2008). Degarelix: a novel gonadotropin-releasing hormone (GnRH) receptor blocker–results from a 1-yr, multicentre, randomised, phase 2 dosage-finding study in the treatment of prostate cancer. Eur. Urol. 54: 805-13.
Ferenc G Rick, Norman L Block, and Andrew V Schall, yAn update on the use of degarelix in the treatment of advanced hormone-dependent prostate cancer. Onco Targets Ther. 2013; 6: 391402.