CurrentmhnPolicy CP.PHAR.529

Clinical Policy: Relugolix (Orgovyx), Relugolix/Estradiol/Norethinedrone (Myfembree)

Pharmacy clinical policy describing medical necessity criteria, initial and continuation approval requirements, dosing limits, prescribing specialty requirements, duration limits, contraindications, and alternatives for Orgovyx and Myfembree across Commercial, HIM, and Medicaid lines of business.

Policy Summary

Payermhn

PolicyClinical Policy: Relugolix (Orgovyx), Relugolix/Estradiol/Norethinedrone (Myfembree)

Policy CodePolicy CP.PHAR.529

Change TypeClarified/Updated criteria and contraindications; added IL step therapy bypass

Effective DateJun 1, 2021

Next Review Date

Key ActionProvider must submit documentation (office notes, labs, or other clinical information) supporting that member has met all approval criteria.

POLICY UPDATE CHANGES

Added step therapy bypass for IL HIM per IL HB 5395.

Updated Appendix C to include hypersensitivity contraindication for Orgovyx per updated prescribing information (2Q2024).

Criteria added for endometriosis pain and alignment changes for prescribers and duration limits (RT4 08.29.22).

3Covered Indications

24 monthsMax Myfembree duration

120 mgStd Orgovyx dose

360 mg

Coverage Summary

Policy Number CP.PHAR.529, Effective Date 2021-06-01. Coverage stance: covered with criteria for relugolix-containing products Orgovyx and Myfembree across Commercial, HIM, and Medicaid. Covered indications include: Orgovyx for treatment of adult patients with advanced prostate cancer, and Myfembree in premenopausal women for management of heavy menstrual bleeding associated with uterine leiomyomas (fibroids) and for moderate to severe pain associated with endometriosis. The policy describes medical necessity criteria, initial and continuation approval requirements, dosing and duration limits, prescribing specialty requirements, contraindications, and alternatives for both products across the listed lines of business.

Key thresholds

Age requirement≥ 18 years

Orgovyx loading dose limit≤ 360 mg (3 tablets) on first day

Orgovyx maintenance dose limits≤ 120 mg (1 tablet) per day; ≤ 240 mg (2 tablets) per day if coadministered with rifampin and unavoidable

Myfembree daily dose limit≤ 40 mg relugolix (1 tablet) per day

Myfembree total duration limit≤ 24 cumulative months

Trial requirement for HMB step therapy3-month trial of combination estrogen-progestin contraceptive (note: step therapy bypass for Illinois HIM effective 1/1/2026 per IL HB 5395)

Trial requirement for endometriosis pain3-month trial within the last year of an NSAID or a progestin (oral or depot), unless contraindicated

Initial Therapy Criteria

Continuation Therapy Criteria

Diagnoses / Indications Not Authorized

Provider Actions & Prior Authorization

Prior Authorization

Prior authorization requirement

Orgovyx and Myfembree require prior authorization. Approval is granted only when the request meets the listed initial or continuation criteria for the requested indication. Approval durations are up to 12 months for initial and continued therapy; total Myfembree therapy should not exceed 24 cumulative months.

Documentation Required

Submit supporting documentation

Submit supporting clinical documentation such as office chart notes, laboratory results, or other relevant clinical information demonstrating that the member meets all approval criteria (diagnosis, prescriber specialty, prior therapy trials, dose limits, and duration limitations).

Applicable Codes

No specific procedure/drug codes listed in policy textmixed

No codes listed

Clinical Evidence & References

Evidence and references include: Prescribing information (Myfembree) — July 2024; Prescribing information (Orgovyx) — October 2024; and NCCN sources including the Drugs & Biologics Compendium and Prostate Cancer Version 1.2025. The policy notes the Myfembree prescribing information includes a 24-month bone loss risk limitation on use.

Background

Relugolix is a GnRH receptor antagonist. Orgovyx (relugolix) is FDA-approved for treatment of adult patients with advanced prostate cancer. Myfembree (relugolix/estradiol/norethindrone) is FDA-approved in premenopausal women for management of heavy menstrual bleeding due to uterine fibroids and for moderate to severe endometriosis-associated pain. Use of Myfembree should be limited to 24 months because of the risk of continued bone loss which may not be reversible.

Revision History

08.29.22material_change

RT4 08.29.22: Criteria added for endometriosis-associated pain indication for Myfembree and alignment changes including prescriber options and addition of a 24-month total therapy limit.

2Q2024revised

2Q2024 annual review: Appendix C updated to add a hypersensitivity contraindication for Orgovyx per updated prescribing information; no significant clinical policy statement changes.

06.25.25clarifiedLatest

Added step therapy bypass for Illinois HIM per IL HB 5395 effective 1/1/2026; clarifies that step therapy requirements do not apply for Illinois HIM requests as of 1/1/2026.

Step Therapy

Step therapy for Myfembree

For Myfembree requests for heavy menstrual bleeding or endometriosis pain, the policy requires failure of a 3-month trial of specified therapies before approval: a 3-month trial of a combination estrogen–progestin contraceptive agent for heavy menstrual bleeding, and a 3-month trial within the last year of either an NSAID or an oral/depot progestin for endometriosis pain. For Illinois HIM requests, these step therapy requirements do not apply as of 1/1/2026 per IL HB 5395.

Heavy menstrual bleeding: 3-month trial of combination estrogen–progestin contraceptive required
Endometriosis pain: 3-month trial within the last year of an NSAID or oral/depot progestin required
Illinois HIM: step therapy bypass effective 1/1/2026 per IL HB 5395