HERO STUDY DESIGN

The efficacy and safety of ORGOVYX were evaluated in a multinational, phase 3, randomized, open-label, parallel-group study^1,2

Schematic design of the HERO study evaluating ORGOVYX and leuprolide

SC=subcutaneous.

*Two patients in each arm did not receive the study treatment and were not included.

^†The dosage of leuprolide was 11.25 mg in Japan and Taiwan, per local guidelines, and is not recommended for this indication in the United States.

ENDPOINTS^1,2

Primary endpoint:

Sustained testosterone suppression rate (defined as the cumulative probability of testosterone suppression to <50 ng/dL while on study treatment from Day 29 through Week 48)

Key secondary endpoints include:

Testosterone suppression rates on Day 4 and Day 15 (defined as testosterone concentrations <50 ng/dL)
PSA response rate on Day 15 (>50% decrease from baseline), confirmed on Day 29
Profound testosterone suppression rate on Day 15 (defined as testosterone concentrations <20 ng/dL)

Testosterone recovery substudy:

Cumulative probability of testosterone recovery to 280 ng/dL at the 90-day follow-up in 184 patients who completed 48 weeks of treatment and who did not receive subsequent androgen deprivation therapy for at least 90 days after discontinuation^‡

PSA=prostate-specific antigen.

^‡This endpoint was analyzed for exploratory purposes without formal testing.

PATIENT ENROLLMENT

HERO enrolled patients across different clinical disease presentations of advanced prostate cancer¹

Key enrollment criteria

Key inclusion criteria^1,2

Men ≥18 years of age with confirmed adenocarcinoma of the prostate
Requiring at least 1 year of continuous androgen deprivation therapy with 1 of the following clinical disease presentations:
- Evidence of biochemical (PSA) or clinical relapse following local primary intervention with curative intent
- Newly diagnosed androgen-sensitive metastatic disease
- Advanced localized disease unlikely to be cured by local primary intervention with curative intent
Serum testosterone ≥150 ng/dL
Serum PSA >2.0 ng/mL^§
ECOG score 0/1

Key exclusion criteria^2,3

Patients likely to require chemotherapy or surgical therapy for symptomatic disease management within 2 months of initiating androgen deprivation therapy
Previously received GnRH analog or other form of androgen deprivation therapy for >18 months total duration
- If androgen deprivation therapy was received for ≤18 months total duration, then patients must have completed treatment ≥3 months prior to baseline, or at least as long as the dosing interval of the depot formulation received
Significant cardiovascular risk conditions
- Myocardial infarction or thromboembolic events within 6 months
- Arrhythmias
- Uncontrolled hypertension

ECOG=Eastern Cooperative Oncology Group; GnRH=gonadotropin-releasing hormone.

^§When applicable, post radical prostatectomy of >0.2 ng/mL or post radiotherapy, cryotherapy, or high-frequency ultrasound >2.0 ng/mL above the postinterventional nadir.

PATIENT POPULATION

Baseline characteristics were balanced between treatment arms²

CARDIOVASCULAR RISK FACTORS AT BASELINE²

80% of men had cardiovascular or cerebrovascular risk factors such as diabetes and hypertension
67% had lifestyle risk factors such as a history of smoking or obesity
14% had a history of myocardial infarction or stroke

See Key Enrollment Criteria above for exclusion criteria about cardiovascular risk conditions.

Select baseline characteristics

Table showing the baseline characteristics for the men participating in the ORGOVYX HERO study

^||Biochemical relapse was defined by a rising PSA level.

^¶ECOG performance status ranges from 0 to 5, with higher scores reflecting greater disability.

^#One patient in the leuprolide group had a surgical vascular procedure on his leg and was given an ECOG score of 3 at screening because of the use of crutches. By the baseline Day 1 visit, the patient no longer used crutches, and his ECOG score had improved to 0.

**Patients with multiple risk factors were counted only once.

^††Included current/past tobacco smoking, heavy alcohol use, and a BMI >30 kg/m².

^‡‡Included hypertension; dyslipidemia; diabetes; a history of myocardial infarction or cardiovascular disease; a history of stroke, transient ischemic attack, or cerebral hemorrhage; peripheral arterial disease; atrial fibrillation and other arrhythmias; heart valve disease; chronic obstructive pulmonary disease; chronic kidney disease; chronic liver disease; carotid artery stenosis or occlusion; venous thromboembolic events; and heart failure.

^§§Search criteria included "myocardial infarction" (broad standardized MedDRA query), "central nervous system hemorrhages and cerebrovascular conditions" (broad standardized MedDRA query).

MedDRA=Medical Dictionary for Regulatory Activities; SD=standard deviation.

Sustained Testosterone Suppression to <50 ng/dL

ORGOVYX achieved sustained testosterone suppression in 97% of men¹

97% of men achieved and maintained testosterone suppression to <50 ng/dL from Day 29 through Week 48 with ORGOVYX
- 89% of men treated with leuprolide sustained testosterone suppression from Day 29 through Week 48

MAJOR EFFICACY OUTCOME MEASURE: SUSTAINED TESTOSTERONE SUPPRESSION RATE (TESTOSTERONE LEVELS <50 ng/dL FROM DAY 29 THROUGH WEEK 48)¹

Bar chart showing sustained testosterone suppression rate of ORGOVYX and leuprolide from Day 29 to Week 48

CI=confidence interval.

^aKaplan-Meier estimates within each group.

^bThe testosterone suppression rate of the subgroup of patients receiving leuprolide 22.5 mg (n=264) was 88.0% (95% CI: 83.4-91.4).

THINK ORAL ORGOVYX FOR ANDROGEN DEPRIVATION THERAPY

Rapid Testosterone Suppression

ORGOVYX suppressed testosterone with no initial surge and sustained suppression throughout the study^1,2

On Day 4: 56% of men treated with ORGOVYX achieved testosterone suppression to <50 ng/dL^c
- 0% of men treated with leuprolide had testosterone levels <50 ng/dL on Day 4

MEAN TESTOSTERONE CONCENTRATIONS FROM BASELINE THROUGH WEEK 48²

Line chart showing change from baseline in mean testosterone concentrations with ORGOVYX and leuprolide through Week 49

Adapted with permission from the New England Journal of Medicine.

On Day 15: 99% of men treated with ORGOVYX achieved testosterone suppression to <50 ng/dL^c
- 12% of men treated with leuprolide had testosterone levels <50 ng/dL on Day 15

^cKaplan-Meier estimates within each group.

CONSIDER ORAL ORGOVYX FOR PATIENTS WHO NEED RAPID TESTOSTERONE SUPPRESSION

PROFOUND testosterone suppression to <20 ng/dL

ORGOVYX achieved profound testosterone suppression, defined as testosterone concentrations <20 ng/dL¹

On Day 15: 78% of men treated with ORGOVYX achieved profound testosterone suppression to <20 ng/dL^d
- 1% of men treated with leuprolide had testosterone levels <20 ng/dL on Day 15
On Day 29: 95% of men treated with ORGOVYX achieved profound testosterone suppression to <20 ng/dL^d
- 57% of men treated with leuprolide had testosterone levels <20 ng/dL on Day 29

PERCENTAGE OF MEN WITH TESTOSTERONE CONCENTRATIONS <20 ng/dL

Bar chart showing testosterone suppression >20 ng/dL with ORGOVYX and leuprolide on Days 4, 8, 15, and 29

^dKaplan-Meier estimates within each group.

CONSIDER ORGOVYX FOR EFFECTIVE AND
PROFOUND TESTOSTERONE SUPPRESSION TO <20 ng/dL

PSA REDUCTION

ORGOVYX lowered PSA levels after 2 weeks and maintained PSA suppression through 48 weeks¹

ORGOVYX DEMONSTRATED PSA REDUCTIONS FROM BASELINE AVERAGE OF 104.2 ng/mL²

Downward arrows depicting ORGOVYX PSA reduction at 2 weeks, 4 weeks, and at 3 months through 48 weeks

PSA results should be interpreted with caution because of the heterogeneity of the patient population studied. No evidence has shown that the rapidity of PSA decline is related to a clinical benefit.¹

TESTOSTERONE RECOVERY

ORGOVYX testosterone recovery 90 days after discontinuation^1,2,4

Testosterone recovery was evaluated in a substudy of 184 patients who completed 48 weeks of treatment^e
90 days after treatment discontinuation, 55% of 137 men treated with ORGOVYX had their testosterone return to above the lower limit of the normal range (>280 ng/dL) or baseline values^f
- 3% of 47 men treated with leuprolide had their testosterone return to above the lower limit of the normal range (>280 ng/dL) or baseline values 90 days after discontinuation

^eThis endpoint was analyzed for exploratory purposes without formal testing. The data from the leuprolide arm were not included in the US Prescribing Information for ORGOVYX.

^fKaplan-Meier estimates within each group.

TESTOSTERONE CONCENTRATIONS IN TESTOSTERONE RECOVERY SUBSTUDY (N=184)²

Line chart showing testosterone recovery with ORGOVYX and leuprolide from end of treatment through 90 days

Adapted with permission from the New England Journal of Medicine.

CONSIDER TESTOSTERONE RECOVERY WHEN PRESCRIBING ANDROGEN DEPRIVATION THERAPY

IMPORTANT SAFETY INFORMATION & INDICATION

Warnings and Precautions

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.

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. Advise males with female partners of reproductive potential to use effective contraception during treatment and for 2 weeks after the last dose of ORGOVYX

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.

Adverse Reactions

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.

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

Drug Interactions

Co-administration of ORGOVYX with a P-gp inhibitor increases the area under the curve (AUC) and maximum concentration (C_max) of ORGOVYX, which may increase the risk of adverse reactions associated with ORGOVYX. Avoid co-administration of ORGOVYX with oral P-gp inhibitors. If co-administration is unavoidable, take ORGOVYX first, separate dosing by at least 6 hours, and monitor patients more frequently for adverse reactions. Treatment with ORGOVYX may be interrupted for up to 2 weeks for a short course of treatment with certain P-gp inhibitors. If treatment with ORGOVYX is interrupted for more than 7 days, resume administration of ORGOVYX with a 360 mg loading dose on the first day, followed by 120 mg once daily.

Co-administration of ORGOVYX with a combined P-gp and strong CYP3A inducer decreases the AUC and C_max of ORGOVYX, which may reduce the effects of ORGOVYX. 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.

INDICATION

ORGOVYX is a gonadotropin-releasing hormone (GnRH) receptor antagonist indicated for the treatment of adult patients with advanced prostate cancer.

Please see full Prescribing Information for ORGOVYX.