From the Guidelines
Orgovyx (relugolix) is a gonadotropin-releasing hormone (GnRH) receptor antagonist that works by directly blocking GnRH receptors in the pituitary gland, preventing the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and leading to rapid suppression of testosterone production by the testes. The mechanism of action of Orgovyx (relugolix) differs from traditional GnRH agonists, which initially cause a testosterone surge before suppression, as it binds competitively to GnRH receptors without causing this initial flare 1. This leads to a rapid decrease in testosterone levels, typically within days, making it a valuable treatment option for advanced prostate cancer where androgen deprivation is necessary.
Key Points
- Orgovyx (relugolix) is administered orally with a loading dose of 360 mg on the first day, followed by 120 mg daily maintenance dosing.
- The oral administration of Orgovyx offers an advantage over injectable GnRH modulators, improving convenience for patients requiring long-term androgen deprivation therapy.
- Common side effects of Orgovyx include hot flashes, fatigue, and potential cardiovascular effects, reflecting the physiological impact of testosterone suppression.
Clinical Considerations
The use of Orgovyx (relugolix) has been evaluated in clinical trials, including the HERO trial, which demonstrated its efficacy in achieving castration rates compared to leuprolide 1. The ESMO clinical practice guideline also recommends the use of relugolix in adult patients with advanced hormone-sensitive prostate cancer, citing its non-inferior and superior castration rate compared to leuprolide 1.
Evidence Summary
The most recent and highest quality study on the mechanism of action of Orgovyx (relugolix) is the 2023 update on treatment recommendations for prostate cancer from the ESMO clinical practice guideline 1. This study provides evidence on the efficacy and safety of relugolix in achieving rapid testosterone suppression and improving quality of life for patients with advanced prostate cancer.
From the FDA Drug Label
Relugolix is a nonpeptide 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. The mechanism of action (MOA) of Orgovyx (relugolix) is as a GnRH receptor antagonist that:
- Competitively binds to pituitary GnRH receptors
- Reduces the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH)
- Consequently reduces testosterone levels 2
From the Research
Mechanism of Action of Orgovyx (Relugolix)
The mechanism of action (MOA) of Orgovyx (relugolix) is as follows:
- Relugolix is an orally active nonpeptide gonadotropin-releasing hormone (GnRH) receptor antagonist 3, 4, 5, 6, 7
- It competitively binds to GnRH receptors, preventing the release of follicle-stimulating hormone and luteinizing hormone (LH) into the systemic circulation 4
- In men, relugolix suppresses testosterone production by inhibiting the release of LH, which is necessary for testosterone production 3, 5, 6, 7
- In women, the reduction in follicle-stimulating hormone concentrations prevents natural follicular development, suppressing ovarian production of estrogen, and together with reductions in LH concentrations, prevent ovulation, corpus luteum formation, and, thereby, the production of progesterone (P) 4
Key Features of Relugolix
- Relugolix leads to rapid inhibition of testicular production of testosterone and its rapid recovery upon discontinuation 5
- It achieves rapid and sustained castration without the testosterone surge associated with LHRH agonists 6, 7
- Relugolix also achieved rapid testosterone recovery, which may potentially reduce ADT-related adverse events and offer opportunities for combination and intermittent therapy strategies 7
- Data from the phase III HERO study demonstrate an improved cardiac safety profile for the GnRH antagonist relugolix compared with the LHRH agonist leuprolide, including a significantly reduced risk for a major adverse cardiovascular event 6, 7