FDA Approves ORGOVYX for Advanced Prostate Cancer

The U.S. Food and Drug Administration (FDA) approved ORGOVYX (relugolix) for the treatment of adult patients with advanced prostate cancer. The approved recommended dosage of ORGOVYX is an initial loading dose of 360 mg on the first day and continue treatment with a 120 mg dose taken orally once daily at approximately the same time each day with or without food.

In patients treated with GnRH receptor agonists and antagonists for prostate cancer, treatment is usually continued upon development of nonmetastatic or metastatic castration-resistant prostate cancer. Additional information regarding dosage and administration as well as warnings and precautions about QT/QTc interval prolongation, embryo-fetal toxicity, and suppression of the pituitary gonadal system can be found in the full prescribing information linked below.

Relugolix is a nonpeptide gonadotropin-releasing hormone (GnRH) receptor antagonist that competitively binds to pituitary GnRH receptors, thereby, reducing the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and consequently testosterone.

After administration of multiple 20 mg to 180 mg doses of relugolix once daily (0.17 to 1.5 times the recommended once daily dose), the AUCtau of relugolix increases approximately proportionally with dose and the Cmax increases greater than proportionally to dose. The accumulation of relugolix upon once daily administration is approximately 2-fold.

The mean (CV%) absolute bioavailability of relugolix is approximately 12% (62%). The median (range) Tmax of relugolix is 2.25 hours (0.5 to 5.0 hours).

Plasma protein binding of relugolix is 68 to 71%, primarily to albumin and to a lesser extent to α1-acid glycoprotein. The mean blood-to-plasma ratio is 0.78.

The mean effective half-life of relugolix is 25 hours and the mean (CV%) terminal elimination half-life is 60.8 (11%) hours. The mean (CV%) total clearance of relugolix is 29.4 (15%) L/h and the renal clearance is 8 L/h.

Relugolix is metabolized primarily by CYP3A and to a lesser extent by CYP2C8 in vitro.

After oral administration of a single 80-mg radiolabeled dose of relugolix, approximately 81% of the radioactivity was recovered in feces (4.2% as unchanged) and 4.1% in urine (2.2% as unchanged).

Relugolix reduced LH, FSH, and testosterone concentrations after oral administration of the recommended loading dose of 360 mg and a 120 mg dose once daily.