Degarelix

Degarelix is a synthetic ten-amino-acid peptide developed by Ferring as FE200486 and marketed as Firmagon. Unlike leuprolide or goserelin, which first stimulate the pituitary before suppressing it, degarelix blocks the Gn RH receptor from the first dose. US approval was in 2008.

Reversible competitive pituitary blockade promptly lowers LH and FSH, followed by castrate testosterone concentrations within days. Because there is no initial testosterone surge, the antiandrogen flare-cover strategy used with agonists is not needed for that mechanism.

Withholding androgen signaling limits hormone-sensitive prostate-cancer activity. In CS21, degarelix was noninferior to leuprolide for maintaining castrate testosterone over 12 months and lowered testosterone and PSA more rapidly in the early weeks. Rapid flare-free suppression is its main differentiating clinical feature.

FDA approved Firmagon in 2008 for advanced prostate cancer. Subcutaneous treatment starts with a loading dose followed by maintenance every 28 days. Fast suppression can be useful in symptomatic or high-burden hormone-sensitive disease.

Common effects include painful, red or swollen injection sites, especially with loading; hot flashes, weight gain, fatigue and liver-enzyme elevations. QT prolongation requires caution with electrolyte abnormalities or other QT-prolonging drugs. Hypersensitivity and reduced bone density from prolonged androgen deprivation are additional concerns.