Drug Monograph

Drug Monograph Drug Name: Orgovyx™ (relugolix) Tablet Drug Class: Endocrine and Metabolic Agents: LHRH, GnRH Antagonists, Oral Prepared For: MO HealthNet Prepared By: Conduent New Criteria Revision of Existing Criteria Executive Summary The purpose of this monograph is to provide a review of new therapy to determine whether the reviewed drug should be made available on an open Purpose: access basis to prescribers, require a clinical edit or require prior authorization for use. Dosage Forms: Orgovyx is available as an oral tablet containing 120 mg of relugolix. Manufacturer: Distributed by: Myovant Sciences, Inc., Brisbane, CA 94005. The efficacy of Orgovyx was demonstrated in a randomized, open-label, parallel group, multinational, phase 3 trial in 930 participants confirmed diagnosis of adenocarcinoma of the prostate. Patients were randomized 2:1 to receive one of the following for 48 weeks: 120 mg Orgovyx orally, once daily or leuprolide injections every 3 months. The primary endpoint assessed was sustained testosterone suppression to castrate levels (<50 Summary of ng/dL) through 48 weeks. Orgovyx met the primary efficacy endpoint, with Findings: 96.7% (95% CI: 94.9%, 97.9%) maintaining castration through 48 weeks compared with 88.8% (95% CI: 84.6%, 91.8%) of men receiving leuprolide. It did not achieve statistical superiority with regard to castration resistance-free survival compared with leuprolide. All other key secondary endpoints showed superiority of Orgovyx over leuprolide (p<0.001). Status Clinical Edit PA Required Recommendation: Open Access PDL Type of PA Appropriate Indications Non-Preferred Criteria: No PA Required Preferred 2021 Conduent Business Services, LLC All Rights Reserved. Purpose The purpose of this monograph is to provide a review of new therapy to determine whether the reviewed drug should be considered a prior authorization drug, a clinical edit drug or an open access drug. While prescription expenditures are increasing at double-digit rates, payers are evaluating ways to control these costs by influencing prescriber behavior and guide appropriate medication usage. This review will assist in the achievement of qualitative and economic goals related to health care resource utilization. Restricting the use of certain medications can reduce costs by requiring documentation of appropriate indications for use, and where appropriate, encourage the use of less expensive agents within a drug class. Introduction (1,2) Prostate cancer is the most common type of cancer in men, besides skin cancer. Approximately 1 in 9 men will be diagnosed with prostate cancer in their lifetime, and about 1 in 41 men will die of this type of cancer. Prostate cancer is more likely to develop in men ≥65 years and of African- American ethnicity. The average age of diagnosis is about 66 years old. There are approximately 3 million men in the U.S. with prostate cancer and about 30,000 are expected to receive androgen deprivation therapy (ADT) as a treatment. Suppressing testosterone levels is one of the primary approaches to systemic treatment of castration-sensitive metastatic prostate cancer and some patients with high-risk localized prostate cancer, which may also include chemotherapy. Medications used to suppress testosterone are GnRH agonists or GnRH antagonists, which vary widely in dosage and duration of action of the formulations. Dosage Form (3) Orgovyx is available as an oral tablet containing 120 mg of relugolix. Manufacturer (3) Distributed by: Myovant Sciences, Inc., Brisbane, CA 94005. Indication(s) (3) Orgovyx is a gonadotropin-releasing hormone (GnRH) receptor antagonist indicated for the treatment of adult patients with advanced prostate cancer. Clinical Efficacy (3,4,5) (mechanism of action/pharmacology, comparative efficacy) Orgovyx is a nonpeptide GnRH receptor antagonist. It competitively binds to pituitary GnRH receptors, thereby reducing luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion, and consequently testosterone. Pharmacokinetics: Absorption Bioavailability 12%, tmax=2.25 hours Metabolism Hepatic (CYP3A, CYP2C8) Excretion Feces (81%), Urine (4.1%) Half-life (terminal elimination) 60.8 hours 2021 Conduent Business Services, LLC All Rights Reserved / Page 2 Clinical Trials Experience STUDY 1 DESIGN Randomized , open-label, parallel group, multinational, phase 3 trial (HERO; (n=930) NCT 03085095) INCLUSION Has histologically or cytologically confirmed diagnosis of CRITERIA adenocarcinoma of the prostate Is a candidate for at least 1 year of continuous androgen deprivation therapy for the management of androgen-sensitive advanced prostate cancer with 1 of the following clinical disease state presentations: o Evidence of biochemical (PSA) or clinical relapse following local primary intervention with curative intent, such as surgery, radiation therapy, cryotherapy, or high-frequency ultrasound and not a candidate for salvage treatment by surgery or o Newly diagnosed androgen-sensitive metastatic disease or o Advanced localized disease unlikely to be cured by local primary intervention with either surgery or radiation with curative intent Has a serum testosterone at the Screening visit of ≥150 ng/dL Has a serum PSA concentration at the Screening visit of >2.0 ng/ml, or when applicable, post radical prostatectomy of >0.2 ng/ml or post radiotherapy, cryotherapy, or high frequency ultrasound >2.0 ng/ml above the post interventional nadir Has an Eastern Cooperative Oncology Group performance status of 0 or 1 at initial screening and at baseline EXCLUSION Patient is likely to require chemotherapy or surgical therapy for CRITERIA symptomatic disease management within 2 months of initiating androgen deprivation therapy Previously received GnRH analog or other form of androgen deprivation therapy (estrogen or antiandrogen) for >18 months total duration. If androgen deprivation therapy was received for ≤18 months total duration, then that therapy must have been completed at least 3 months prior to baseline. If the dosing interval of the depot is longer than 3 months, then the prior androgen deprivation therapy must have been completed at least as long as the dosing interval of the depot Previous systemic cytotoxic treatment for prostate for prostate cancer Metastases to brain per prior clinical evaluation Participants with myocardial infarction, unstable ischemic heart disease, cerebrovascular events, or any significant cardiac condition within the prior 6 months Active conduction system abnormalities Uncontrolled hypertension TREATMENT Patients were randomized 2:1 to receive one of the following for 48 REGIMEN weeks: 120 mg relugolix orally, once daily (n=622) Leuprolide injections every 3 months (n=308) RESULTS The primary endpoint assessed was sustained testosterone suppression to castrate levels (<50 ng/dL) through 48 weeks. 2021 Conduent Business Services, LLC All Rights Reserved / Page 3 Relugolix Leuprolide Mean (n=622) (n=308) Difference Percent of men that maintained castration 96.7 88.8 7.9% through 48 weeks 95% Confidence 94.9, 97.9 84.6, 91.8 4.1, 11.8 Interval Secondary endpoints include: confirmed PSA response rate, profound castration rate, FSH level, castration resistance-free survival (RFS) in patients with and without metastases, testosterone recovery time, and time to PSA progression, among others. Orgovyx did not achieve statistical superiority with regard to castration RFS compared with leuprolide. All other key secondary endpoints showed superiority of Orgovyx over leuprolide (p<0.001). SAFETY Discussed in the Adverse Effects section below. Contraindications (3,4) None (3,4) Warnings and Precautions QT/QTc Interval Prolongation: Androgen deprivation therapy may prolong the QT interval. Embryo-Fetal Toxicity: Orgovyx can cause fetal harm. Advise males with female partners of reproductive potential to use effective contraception. Adverse Effects (3,4) Most common, ≥ 10% Orgovyx Leuprolide Acetate (n =622) % (n=308) % Hot flush 54 52 Glucose increased 44 54 Triglycerides increased 35 36 Musculoskeletal pain 30 29 Hemoglobin decreased 28 29 Alanine aminotransferase (ALT) 27 28 increased Fatigue 26 24 Aspartate aminotransferase (AST) 18 19 increased Constipation 12 10 Diarrhea 12 7 Serious adverse reactions occurring 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 2021 Conduent Business Services, LLC All Rights Reserved / Page 4 (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%). The incidence of major adverse cardiovascular events (MACE) was 2.7% in the Orgovyx arm and 6.2% in the leuprolide arm. Drug Interactions (3,4) P-gp Inhibitors: Avoid co-administration. If unavoidable, take Orgovyx first, separate dosing by at least 6 hours, and monitor patients more frequently for adverse reactions. Combined P-gp and Strong CYP3A Inducers: Avoid co-administration. If unavoidable, increase the Orgovyx dose to 240 mg once daily. Dosage and Administration (3,4) Loading dose of 360 mg on Day 1 120 mg taken once daily, at approximately the same time each day Can be taken with or without food. Do not crush or chew tablets, swallow whole. Cost Generic Name Brand Name Manufacturer Dose Cost**/ Month Relugolix Orgovyx Myovant 360 mg on day 1, $2,313 Sciences then 120 mg daily Leuprolide Lupron Depot AbbVie 22.5 mg IM every 3 $1,767.47

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