CurrentBlue Cross Blue Shield - IowaPolicy 05.04.17

Oral gonadotropin-releasing hormone antagonists (elagolix, relugolix) for endometriosis and uterine fibroids — coverage criteria

Medical policy governing coverage and medical necessity criteria for Orilissa (elagolix), Oriahnn (elagolix formulations), and Myfembree (relugolix/estradiol/norethindrone) for premenopausal women with endometriosis-related pain or heavy menstrual bleeding from uterine leiomyomas. Affects prescribers and pharmacy/prior authorization processes for Wellmark members.

Policy Summary

PayerBlue Cross Blue Shield - Iowa

PolicyOral GnRH antagonists (elagolix, relugolix) for endometriosis and uterine fibroids

Policy CodePolicy 05.04.17

Change TypeNo material change

Effective DateMar 18, 2025

Next Review DateJan 1, 2026

Key ActionSubmit prior authorization with required documentation including diagnosis, prior therapy trials/durations, pregnancy status, hepatic function, and osteoporosis/BMD status.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

24 momax cumulative duration (elagolix/relugolix)

6 momax Orilissa 200 mg duration

56/28dOrilissa 200 mg qty limit

28/28dOrilissa 150 mg / Myfembree qty

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Coverage and Medical Necessity Criteria

Initial Therapy — Orilissa

Covered when ALL of the following are met:

Orilissa initial

Dosing/Hepatic option 1: Request is for 150 mg once daily for a maximum of 24 months and the patient has mild (Child-Pugh class A) or no hepatic impairment.
Dosing/Hepatic option 2: Request is for 200 mg twice daily for a maximum of 6 months, the patient has mild (Child-Pugh class A) or no hepatic impairment, and the indication includes dyspareunia.
Dosing/Hepatic option 3: Request is for 150 mg once daily for a maximum of 6 months and the patient has moderate hepatic impairment (Child-Pugh class B).

Initial Therapy — Oriahnn (fibroids)

Covered when ALL of the following are met:

Oriahnn initial: Diagnosis of heavy menstrual bleeding due to uterine leiomyomas (fibroids); patient has not already received ≥24 months of treatment with elagolix- and/or relugolix-containing products OR has not already received ≥6 months of treatment with Orilissa 200 mg twice daily; patient is premenopausal; patient is not pregnant and does not have undiagnosed abnormal uterine bleeding; patient has tried and had an inadequate response or intolerance to a 3-month trial of BOTH tranexamic acid tablets AND a hormonal contraceptive (e.g., combined oral contraceptives, depot medroxyprogesterone, norethindrone acetate, etonogestrel implant, etc.), OR has a documented contraindication to these agents, OR is currently receiving the requested product through insurance and experiencing benefit (excludes samples or manufacturer assistance); patient does not have osteoporosis or any known hepatic impairment or disease; patient does not have current or history of high-risk arterial, venous thrombotic, or thromboembolic disorders and is not at increased risk for these events; patient does not have current or history of breast cancer or other hormonally-sensitive malignancy.

Initial Therapy — Myfembree (fibroids)

Covered when ALL of the following are met:

Myfembree initial (fibroids): Diagnosis of heavy menstrual bleeding due to uterine leiomyomas (fibroids); patient has not already received ≥24 months of treatment with elagolix- and/or relugolix-containing products OR has not already received ≥6 months of treatment with Orilissa 200 mg twice daily; patient is premenopausal; patient is not pregnant and does not have undiagnosed abnormal uterine bleeding; patient has tried and had an inadequate response or intolerance to a 3-month trial of BOTH tranexamic acid tablets AND a hormonal contraceptive (e.g., combined oral contraceptives, depot medroxyprogesterone, norethindrone acetate, etonogestrel implant, etc.), OR has a documented contraindication to these agents, OR is currently receiving the requested product through insurance and experiencing benefit (excludes samples or manufacturer assistance); patient does not have osteoporosis or any known hepatic impairment or disease; patient does not have current or history of high-risk arterial, venous thrombotic, or thromboembolic disorders and is not at increased risk for these events; patient does not have current or history of breast cancer or other hormonally-sensitive malignancy.

Initial Therapy — Myfembree (endometriosis)

Covered when ALL of the following are met:

Myfembree initial (endometriosis): Diagnosis of moderate to severe pain associated with endometriosis; patient has not already received ≥24 months of treatment with elagolix- and/or relugolix-containing products OR has not already received ≥6 months of treatment with Orilissa 200 mg twice daily; patient is premenopausal; patient is not pregnant; patient has tried and had an inadequate response or intolerance to a 3-month trial of at least one hormonal contraceptive (e.g., combined oral contraceptives, depot medroxyprogesterone, norethindrone acetate, etonogestrel implant, etc.); patient does not have osteoporosis or any known hepatic impairment or disease; patient has not received the maximum recommended treatment course of certain GnRH analogues (12 months of Lupron Depot or Lupaneta Pack OR 6 months of Synarel or Zoladex); patient does not have current or history of high-risk arterial, venous thrombotic, or thromboembolic disorders and is not at increased risk for these events; patient does not have current or history of breast cancer or other hormonally-sensitive malignancy.

Continuation Therapy

Covered when ALL of the following are met for continuation:

Orilissa continuation: Request is for continuation of 150 mg once daily dose; patient is not pregnant; patient does not have moderate hepatic impairment (Child-Pugh class B); patient has experienced a clinically significant improvement in endometriosis-associated pain; cumulative treatment duration has not exceeded a total of 24 months. Approval will be for up to 18 months.

Myfembree continuation (endometriosis): Patient meets all initial criteria for Myfembree; patient has experienced a clinically significant improvement in endometriosis-associated pain; cumulative treatment duration has not exceeded a total of 24 months. Approval will be for up to 18 months.

Myfembree/Oriahnn continuation (fibroids): Patient meets all initial criteria for the requested fibroid therapy; patient has experienced a noticeable clinical benefit since initiating therapy (e.g., measured by pictorial blood loss assessment chart, menstrual pictogram, pad count, self-perception, etc.); cumulative treatment duration has not exceeded a total of 24 months. Approval will be for up to 18 months. Note: members receiving samples or manufacturer assistance must meet initial criteria.

Patients with known osteoporosis are contraindicated for treatment with elagolix- or relugolix-containing products and will not be approved. The clinical rationale notes that these agents can cause a decrease in bone mineral density (BMD), that BMD loss increases with duration of use and may not be completely reversible, and therefore use is contraindicated in individuals with established osteoporosis.

This policy does not list specific procedure or billing codes within the coverage criteria text. Providers should report services using the appropriate coding systems — CPT, HCPCS (alpha-numeric level II), revenue, and ICD diagnostic codes — as applicable for the service rendered and the member's condition.

Do not approve therapy if the member has already received the maximum recommended prior treatment courses or cumulative exposure to GnRH analogues. Specifically, requests will be denied when cumulative prior exposure is ≥24 months of elagolix- and/or relugolix-containing products or ≥6 months of Orilissa 200 mg twice daily, and Myfembree will not be approved if the patient has already received maximum recommended courses of certain injectable or intranasal GnRH analogues (e.g., 12 months Lupron Depot or Lupaneta Pack, or 6 months Synarel or Zoladex).

Procedure and Billing Codes

Prior Authorization, Documentation, and Billing Actions

Prior Authorization

Prior Authorization Required

Prior Authorization Required — initial and continuation approvals are typically granted for up to 6 months (initial) and up to 18 months (continuation) depending on the product and indication. Requests must demonstrate the member meets the policy's clinical criteria, including prescriber specialty when required.

Initial approvals generally granted for up to 6 months.
Continuation approvals generally granted for up to 18 months where continuation criteria are met.
Prescriber requirement: initial requests for certain products must be prescribed by or in consultation with an obstetrician-gynecologist.

Step Therapy

Step Therapy Requirements

Step therapy: the member must have tried and had an inadequate response or intolerance to a 3-month trial of at least one hormonal contraceptive for endometriosis-related pain indications; for heavy menstrual bleeding due to fibroids, the member must have tried tranexamic acid AND a hormonal contraceptive (or have documentation of contraindication/intolerance to these therapies).

Clinical Background and Scope

Oral GnRH antagonists — elagolix (Orilissa, Oriahnn) and relugolix (Myfembree) — are indicated in premenopausal women for two primary clinical uses addressed by this policy: management of moderate to severe endometriosis-associated pain and treatment of heavy menstrual bleeding due to uterine leiomyomas (fibroids). Use is limited by risks to bone mineral density and hepatic considerations; therefore the policy imposes step-therapy, prior authorization, contraindication, and cumulative duration limits to align with product labeling and to mitigate long-term BMD loss.

Key Definitions and Limits

Maximum recommended treatment duration

Maximum cumulative duration for elagolix- or relugolix-containing products24 months cumulative lifetime maximum

Maximum duration for Orilissa 200 mg twice daily6 months maximum

Orilissa 150 mg dosing durationUp to 24 months for 150 mg once daily when appropriate

Contraindications and clinical limitations

Known osteoporosisContraindicated — elagolix- and relugolix-containing products will not be approved in patients with diagnosed osteoporosis

Severe hepatic impairmentAvoid use in patients with severe hepatic impairment (Child-Pugh class C); dosing/duration differ by hepatic function