Orgovyx

ORGOVYX- relugolix tablet, film coated
Myovant Sciences, Inc.

1 INDICATIONS AND USAGE

ORGOVYX is indicated for the treatment of adult patients with advanced prostate cancer.

2 DOSAGE AND ADMINISTRATION

2.1 Recommended Dosage

Initiate treatment of ORGOVYX with a 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.

ORGOVYX can be taken with or without food [see Clinical Pharmacology (12.3)]. Instruct patients to swallow tablets whole and not to crush or chew tablets.

Advise patients to take a missed dose of ORGOVYX as soon as they remember. If the dose was missed by more than 12 hours, patients should not take the missed dose and resume with the next scheduled dose.

If treatment with ORGOVYX is interrupted for greater than 7 days, restart ORGOVYX with a loading dose of 360 mg on the first day, and continue with a dose of 120 mg once daily.

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.

2.2 Dose Modification for Use with P-gp Inhibitors

Avoid co-administration of ORGOVYX with oral P-gp inhibitors. If co-administration is unavoidable, take ORGOVYX first and separate dosing by at least 6 hours [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)]. Treatment with ORGOVYX may be interrupted for up to two weeks if a short course of treatment with a P-gp inhibitor is required.

2.3 Dose Modification for Use with Combined P-gp and Strong CYP3A Inducers

Avoid co-administration of ORGOVYX with combined P-gp and strong CYP3A inducers. If co-administration is unavoidable, increase the ORGOVYX dose to 240 mg once daily. After discontinuation of the combined P-gp and strong CYP3A inducer, resume the recommended ORGOVYX dose of 120 mg once daily [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)].

3 DOSAGE FORMS AND STRENGTHS

Tablets: 120 mg, light red, almond-shaped, film-coated, and debossed with “R” on one side and “120” on the other side.

4 CONTRAINDICATIONS

​ ORGOVYX is contraindicated in patients with severe hypersensitivity to relugolix or to any of the product components.

5 WARNINGS AND PRECAUTIONS

5.1 QT/QTc Interval Prolongation

Androgen deprivation therapy, such as ORGOVYX may prolong the QT/QTc interval. Providers should consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients with congenital long QT syndrome, congestive heart failure, or frequent electrolyte abnormalities and in patients taking drugs known to prolong the QT interval. Electrolyte abnormalities should be corrected. Consider periodic monitoring of electrocardiograms and electrolytes [see Clinical Pharmacology (12.2)].

5.2 Hypersensitivity Reactions

​ ORGOVYX is contraindicated in patients with severe hypersensitivity to relugolix or any of the product components [see Contraindications (4)]. Hypersensitivity reactions, including pharyngeal edema and other serious cases of angioedema, have been reported in postmarketing in patients treated with ORGOVYX.

In the HERO study, patients treated with relugolix reported angioedema (0.2%) [see Clinical Trials Experience (6.1)].

Advise patients who experience any symptoms of hypersensitivity to temporarily discontinue ORGOVYX and promptly seek medical care.

Discontinue ORGOVYX for severe hypersensitivity reactions and manage as clinically indicated.

5.3 Embryo-Fetal Toxicity

The safety and efficacy of ORGOVYX have not been established in females. Based on findings in animals and mechanism of action, ORGOVYX can cause fetal harm and loss of pregnancy when administered to a pregnant female. In an animal reproduction study, oral administration of relugolix to pregnant rabbits during the period of organogenesis caused embryo-fetal lethality at maternal exposures that were 0.3 times the human exposure at the recommended dose of 120 mg daily based on area under the curve (AUC). Advise males with female partners of reproductive potential to use effective contraception during treatment and for 2 weeks after the last dose of ORGOVYX [see Use in Specific Populations (8.1, 8.3) and Clinical Pharmacology (12.1)].

5.4 Laboratory Testing

Therapy with ORGOVYX results in suppression of the pituitary gonadal system. Results of diagnostic tests of the pituitary gonadotropic and gonadal functions conducted during and after ORGOVYX may be affected. The therapeutic effect of ORGOVYX should be monitored by measuring serum concentrations of prostate specific antigen (PSA) periodically. If PSA increases, serum concentrations of testosterone should be measured.

6 ADVERSE REACTIONS

The following clinically significant adverse reactions are described elsewhere in the labeling:

• QT/QTc Interval Prolongation [see Warnings and Precautions (5.1)].

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety of ORGOVYX was evaluated in HERO, a randomized (2:1), open-label, clinical study in patients with advanced prostate cancer [see Clinical Studies (14)]. Patients received orally administered ORGOVYX as a loading dose of 360 mg on the first day followed by 120 mg taken orally once daily (n = 622) or received leuprolide acetate administered by depot injection at doses of 22.5 mg (n = 264) or 11.25 mg (n = 44) per local guidelines every 12 weeks (n = 308). Leuprolide acetate 11.25 mg is a dosage regimen that is not recommended for this indication in the US. Among patients who received ORGOVYX, 91% were exposed for at least 48 weeks. Ninety-nine (16%) patients received concomitant radiotherapy and 17 (3%) patients received concomitant enzalutamide with ORGOVYX.

Serious adverse reactions occurred in 12% of patients receiving ORGOVYX. Serious adverse reactions in ≥ 0.5% of patients included myocardial infarction (0.8%), acute kidney injury (0.6%), arrhythmia (0.6%), hemorrhage (0.6%), and urinary tract infection (0.5%). Fatal adverse reactions occurred in 0.8% of patients receiving ORGOVYX including metastatic lung cancer (0.3%), myocardial infarction (0.3%), and acute kidney injury (0.2%). Fatal and non-fatal myocardial infarction and stroke were reported in 2.7% of patients receiving ORGOVYX.

Permanent discontinuation of ORGOVYX due to an adverse reaction occurred in 3.5% of patients. Adverse reactions which resulted in permanent discontinuation of ORGOVYX in ≥ 0.3 % of patients included atrioventricular block (0.3%), cardiac failure (0.3%), hemorrhage (0.3%), increased transaminases (0.3%), abdominal pain (0.3%), and pneumonia (0.3%).

Dosage interruptions of ORGOVYX due to an adverse reaction occurred in 2.7% of patients. Adverse reactions which required dosage interruption in ≥ 0.3% of patients included fracture (0.3%).

The most common adverse reactions (≥ 10%) and laboratory abnormalities (≥ 15%), were hot flush (54%), glucose increased (44%), triglycerides increased (35%), musculoskeletal pain (30%), hemoglobin decreased (28%), alanine aminotransferase increased (ALT) (27%), fatigue (26%), aspartate aminotransferase increased (AST) (18%), constipation (12%), and diarrhea (12%).

Table 1 summarizes the adverse reactions in HERO.

Table 1: Adverse Reactions ( ≥ 10%) of Patients with Advanced Prostate Cancer Who Received ORGOVYX in HERO

Adverse Reaction	ORGOVYX N = 622		Leuprolide Acetate N = 308
	All Grades (%)	Grade 3-4 (%)	All Grades (%)	Grade 3-4 (%)
* Includes arthralgia, back pain, pain in extremity, musculoskeletal pain, myalgia, bone pain, neck pain, arthritis, musculoskeletal stiffness, non-cardiac chest pain, musculoskeletal chest pain, spinal pain, and musculoskeletal discomfort. † Includes fatigue and asthenia. ‡ Includes diarrhea and colitis.
Vascular disorders
Hot flush	54	0.6	52	0
Musculoskeletal and connective tissue disorders
Musculoskeletal pain *	30	1.1	29	1.6
General
Fatigue †	26	0.3	24	0
Gastrointestinal disorders
Diarrhea ‡	12	0.2	7	0
Constipation	12	0	10	0

Clinically relevant adverse reactions in < 10% of patients who received ORGOVYX included increased weight, insomnia, gynecomastia, hyperhidrosis, depression, decreased libido, and angioedema.

Table 2 summarizes the laboratory abnormalities in HERO.

Table 2: Select Laboratory Abnormalities ( ≥ 15%) That Worsened from Baseline in Patients with Advanced Prostate Cancer Who Received ORGOVYX in HERO

	ORGOVYX *		Leuprolide Acetate *
Laboratory Test	All Grades (%)	Grade 3-4 (%)	All Grades (%)	Grade 3-4 (%)
* The denominator used to calculate the rate varied from 611 to 619 in the ORGOVYX arm and from 301 to 306 in the leuprolide arm based on the number of patients with a baseline value and at least one post-treatment value.
Chemistry
Glucose increased	44	2.9	54	6
Triglycerides increased	35	2	36	0.7
ALT increased	27	0.3	28	0
AST increased	18	0	19	0.3
Hematology
Hemoglobin decreased	28	0.5	29	0.7