Effective Date

Date of Origin   

04-01-2025           

Myfembree®

(relugolix, estradiol hemihydrate, norethindrone acetate)

Tablet

Management of heavy menstrual bleeding associated with uterine leiomyomas (fibroids) in premenopausal patients

Management of moderate to severe pain associated with endometriosis in premenopausal patients

Limitations of Use: Use of Myfembree should be limited to 24 months due to the risk of continued bone loss which may not be reversible.

3

Oriahnn®

(elagolix, estradiol, norethindrone acetate)

Capsule

Management of heavy menstrual bleeding associated with uterine leiomyomas (fibroids) in premenopausal patients

Limitations of Use: Use of Oriahnn should be limited to 24 months due to the risk of continued bone loss, which may not be reversible.

2

Orilissa®

(elagolix)

Tablet

Management of moderate to severe pain associated with endometriosis

Limitations of Use: Limit the duration of use based on the dose and coexisting condition (refer to labeling for additional details).

1

Endometriosis

Endometriosis is an estrogen-dependent, benign, inflammatory disease that affects patients during their premenarcheal, reproductive, and postmenopausal hormonal stages. While endometriosis is a common and nonmalignant process, ectopic endometrial tissue and resultant inflammation can cause dysmenorrhea, dyspareunia, chronic pain, and infertility. Symptoms can range from minimal to severely debilitating. While definitive diagnosis of endometriosis requires tissue biopsy and histologic confirmation, the combination of symptoms, signs, and imaging findings can be used to make a presumptive, nonsurgical diagnosis of endometriosis.(4,5)

The first-line options for the treatment of mild and moderate pain associated with endometriosis include non-steroidal anti-inflammatory drugs (NSAIDs) and hormonal contraceptives as combined (oral, vaginal ring or transdermal), oral progestin-only, levonorgestrel-releasing intrauterine system, or an etonogestrel-releasing subdermal implant. These therapies have low risk with few side effects and provide symptom relief for many patients. For those who have severe pain or continue to experience symptoms on hormonal contraceptive therapy, the use of gonadotropin-releasing hormone (GnRH) antagonists is recommended as second-line (e.g., if hormonal contraceptives or progestins have been ineffective). Patients who do not respond to medical treatment may move on to laparoscopy or hysterectomy for treatment.(5,12)

Uterine Leiomyomas

Uterine Leiomyomas, also known as myomata or fibroids, are the most common gynecologic benign tumors. Uterine leiomyomas are classified based on their location in the uterine wall and are referred to as submucous, intramural, and subserosal. Uterine leiomyomas are monoclonal tumors that arise from the muscular layer of the uterus and consist of large amounts of collagen, fibronectin, and proteoglycan. Leiomyomas can become enlarged causing significant distortion of the uterine surface or cavity.(6,7)

Many patients with uterine leiomyomas are asymptomatic, but symptomatic patients may experience significant symptoms that interfere with daily living. The clinical characteristics can be broken down into three categories:(6)

• Heavy or abnormal uterine bleeding (the most common symptom)
• Pelvic pressure and pain
• Reproductive dysfunction (i.e., infertility, miscarriages, preterm labor)

Uterine leiomyomas are generally diagnosed via pelvic examination and pelvic ultrasound. Other imagining, such as saline-infused sonogram, MRI, and hysteroscopy, are used if further evaluation of the leiomyomas is needed.(8,9)

Hysterectomy is the only definitive treatment and eliminates the possibility of recurrence for patients who do not desire future childbearing or do not wish to retain their uterus. The American College of Gynecology and Obstetrics indicates the following are alternative options to hysterectomy:(9)

• Hormonal contraceptives (combined hormonal contraceptive pills, progestin-only pills, levonorgestrel releasing IUDs) are widely used for control of abnormal menstruation and are often first line therapy, however, they only offer short term relief and direct data to support their effectiveness is limited
• NSAIDs are associated with modest improvement in menstrual bleeding
• Tranexamic acid, an antifibrinolytic medication that prevents fibrin degradation, is an effective treatment for heavy menstrual bleeding, but limited data is associated with a statistically significant decrease in abnormal uterine bleeding
• Gonadotropin releasing hormone antagonists, with hormonal add-back therapy, are recommended for treatment of heavy menstrual bleeding associated with uterine leiomyomas for up to two years
• Gonadotropin releasing hormone agonists, with or without hormonal add-back therapy are recommended for the short-term treatment of abnormal uterine bleeding and uterine enlargement associated with leiomyomas and as a bridge to other treatment strategies
• Uterine artery embolization, laparoscopic radiofrequency ablation, or myomectomy are alternatives for patients who desire uterine preservation and are counseled about the limited available data on reproductive outcomes

Efficacy

Myfembree(3)

The efficacy and safety of Myfembree in patients with heavy menstrual bleeding associated with uterine fibroids were evaluated in two replicate, 24-week, multinational, randomized, double-blind, placebo-controlled studies in a total of 768 premenopausal patients with heavy menstrual bleeding associated with uterine fibroids in Study L1 (NCT03049735) and Study L2 (NCT03103087). For study inclusion, patients had to have uterine fibroids confirmed by ultrasound examination, and menstrual blood loss (MBL) volume of greater than or equal to 80 mL per cycle for two menstrual cycles or greater than or equal to 160 mL during one cycle to be included in the studies. Patients with hemoglobin less than 8.0 g/dL were excluded from the study. Iron therapy was required for patients with hemoglobin greater than or equal to 8 g/dL and less than or equal to 10 g/dL. Patients were allowed, but not required, to take calcium and vitamin D during the study. Treatment was initiated within the first seven days after the onset of menses.

The primary endpoint of both studies was the proportion of patients in the Myfembree group compared with patients in the placebo group, who achieved menstrual blood loss volume of less than 80 mL and at least a 50% reduction from baseline MBL volume over the last 35 days of treatment. Key secondary endpoints were related to amenorrhea, MBL volume, and change in hemoglobin. In both Study L1 and Study L2, a statistically higher proportion of patients treated with Myfembree achieved the primary endpoint of both an MBL volume of less than 80 mL and at least a 50% reduction from baseline in MBL volume over the last 35 days of treatment compared with placebo. In Studies L1 and L2, 50.0% and 50.4% of patients treated with Myfembree, respectively, achieved amenorrhea compared to 6.2% and 3.1% treated with placebo, respectively, over the last 35 days of treatment. The mean MBL volumes in Studies L1 and L2 at baseline were 243.8 mL and 246.7 mL in the Myfembree group and 223.2 mL and 211.8 mL in the placebo group, respectively. The mean reduction in MBL volume from baseline to Week 24 in the Myfembree group was 82.0% in Study L1 and 84.3% in Study L2, compared with placebo which was 19.1% and 15.1%, respectively. A hemoglobin response was defined as a hemoglobin increase greater than 2 g/dL from baseline to Week 24 in the subgroup of patients with anemia at baseline (hemoglobin less than or equal to 10.5 g/dL). A statistically higher proportion treated with Myfembree compared with placebo had greater than 2 g/dL improvement in hemoglobin levels.

The efficacy of Myfembree in premenopausal patients with moderate to severe pain associated with endometriosis was assessed in two 24-week, multinational, randomized, double-blind, placebo-controlled studies; Study S1 (NCT03204318) and Study S2 (NCT03204331). Study S1 included at total of 424 patients and Study S2 a total of 405. For study inclusion, patients had to have endometriosis confirmed by direct visualization during surgery and/or histology in addition to pain associated with endometriosis during a placebo run-in period. Dysmenorrhea (DYS) and non-menstrual pelvic pain (NMPP) were assessed daily using an 11-point numerical rating scale (NRS) ranging from 0 ("no pain") to 10 ("pain as bad as you can imagine"). The co-primary endpoints of studies S1 and S2 were dysmenorrhea and non-menstrual pelvic pain response. Participants in Study S1 showed a 47.6% difference from placebo in dysmenorrhea response and a 18.9% difference in non-menstrual pelvic pain response at week 24, and Study S2 showed differences of 44.6% and 23.4%, respectively.

Orilissa(1,11)

The efficacy of Orilissa 150 mg once daily and 200 mg twice daily for the management of moderate to severe pain associated with endometriosis was demonstrated in two multinational double-blind, placebo-controlled trials in 1686 premenopausal patients (Study EM-1 [NCT01620528] and Study EM-2 [NCT01931670]). Each placebo-controlled trial assessed the reduction in moderate to severe endometriosis-associated pain over 6 months of treatment. Each element is scored from 0 (absent) to 3 (severe) for a maximum total score of 15. Subjects were required to have non-menstrual pelvic pain for at least four days in the preceding 35 days, a bone mineral density (BMD) greater then -1.5, and the diagnosis of endometriosis was surgically confirmed. Patients were excluded if they had clinically significant gynecologic conditions (e.g., persistent or complex ovarian cyst(s), cancer, pelvic inflammatory disease), a history of osteoporosis, or other metabolic bone disease.

The co-primary efficacy endpoints were (1) the proportion of subjects whose dysmenorrhea responded to treatment at Month 3 and (2) the proportion of subjects whose pelvic pain not related to menses (also known as non-menstrual pelvic pain) responded to treatment at Month 3. A higher proportion of patients treated with Orilissa 150 mg once daily or 200 mg twice daily were responders for dysmenorrhea and non-menstrual pelvic pain compared to placebo in a dose-dependent manner at Month 3.

Patients in these studies also provided a daily self-assessment of their endometriosis pain using a numeric rating scale (NRS) that asked subjects to rate their endometriosis pain at its worst over the last 24 hours on a scale from 0 (no pain) to 10 (worst pain ever). In Study EM-1, baseline NRS scores were 5.7 for Orilissa 150 mg once daily, 5.5 for Orilissa 200 mg twice daily and 5.6 for placebo. In Study EM-2, baseline NRS scores were 5.7 for Orilissa 150 mg once daily, 5.3 for Orilissa 200 mg twice daily and 5.6 for placebo. Patients taking Orilissa 150 mg once daily and 200 mg twice daily reported a statistically (p<0.001) significant reduction from baseline in NRS scores compared to placebo at Month 3 in both Studies EM-1 and EM-2 (Study EM-1: 0.7 points for Orilissa 150 mg once daily and 1.3 points for Orilissa 200 mg twice daily; Study EM-2: 0.6 points for Orilissa 150 mg once daily and 1.2 points for Orilissa 200 mg twice daily). In addition, both Orilissa treatment groups showed statistically significantly greater mean decreases from baseline compared to placebo in dysmenorrhea and non-menstrual pelvic pain scores at Month 6.

Oriahnn(2,10)

The efficacy of Oriahnn in the management of heavy menstrual bleeding (HMB) associated with uterine fibroids was demonstrated in two randomized, double-blind, placebo-controlled studies (Study UF-1 [NCT02654054] and Study UF-2 [NCT02691494]) in which 790 premenopausal patients with heavy menstrual bleeding received Oriahnn (elagolix 300 mg, estradiol 1 mg, and norethindrone acetate 0.5 mg in the morning and elagolix 300 mg in the evening) or placebo for 6 months. Patients were eligible if they were premenopausal females, had ultrasound confirmed diagnosis of uterine fibroids with heavy bleeding. Heavy menstrual bleeding at baseline was defined as having at least two menstrual cycles with greater than 80 mL of menstrual blood loss (MBL) as assessed by alkaline hematin (AH) method (an objective, validated measure to quantify MBL volume on sanitary products). Eligible patients were required to complete a washout period if previously treated with hormonal/antihormonal therapies. Patients were excluded if they had persistent or complex ovarian cyst(s), cancer, pelvic inflammatory disease, history of osteoporosis, or a bone mineral density (BMD) T score of -1.5 or less.

The primary endpoint in both studies was the proportion of responders, defined as patients who achieved both 1) MBL volume less than 80 mL at the Final Month and 2) 50% or greater reduction in MBL volume from baseline to the final month. A higher proportion of Oriahnn-treated patients were responders compared to placebo-treated patients.

In Study UF-1, mean baseline MBL was 238 mL for Oriahnn and 255 mL for placebo. In Study UF-2, mean baseline MBL was 228 mL for Oriahnn and 254 mL for placebo. Patients taking Oriahnn had a mean reduction of MBL volume from Baseline to Final Month in both Studies UF-1 and UF-2 compared to patients taking placebo (Study UF-1: -177 mL for Oriahnn and 1 mL for placebo; Study UF-2: -169 mL for Oriahnn and -4 mL for placebo). In Studies UF-1 and UF-2, a greater proportion (57% and 61%, respectively) of patients receiving Oriahnn experienced suppression of bleeding, defined as no bleeding (but spotting allowed), at Final Month, compared to 4% and 5%, respectively, of patients receiving placebo. In Studies UF-1 and UF-2, a greater proportion of Oriahnn-treated patients who were anemic with baseline Hgb less than or equal to 0.5 g/dL achieved an increase greater than 2 g/dL in Hgb from Baseline to Month 6 compared to placebo-treated patients. Over 90% of patients with baseline Hgb less than or equal to 10.5 g/dL took supplemental iron.

Safety

Myfembree has the following boxed warnings:(3)

• Estrogen and progestin combinations, including Myfembree, increase the risk of thrombotic or thromboembolic disorders including pulmonary embolism (PE), deep vein thrombosis (DVT), stroke and myocardial infarction (MI), especially in patients at increased risk for these events.
• Myfembree is contraindicated in patients with current or a history of thrombotic or thromboembolic disorders and in patients at increased risk for these events, including patients over 35 years of age who smoke or patients with uncontrolled hypertension.

Myfembree is contraindicated in patients:(3)

• With a high risk of arterial, venous thrombotic, or thromboembolic disorders. Examples include patients over 35 years of age who smoke, and patients who are known to have:
  • current or history of deep vein thrombosis or pulmonary embolism
  • vascular disease (e.g., cerebrovascular disease, coronary artery disease, peripheral vascular disease)
  • thrombogenic valvular or thrombogenic rhythm diseases of the heart (for example, subacute bacterial endocarditis with valvular disease, or atrial fibrillation)
  • inherited or acquired hypercoagulopathies
  • uncontrolled hypertension
  • headaches with focal neurological symptoms or migraine headaches with aura if over 35 years of age

• Who are pregnant. Exposure to Myfembree early in pregnancy may increase the risk of early pregnancy loss
• With known osteoporosis, because of the risk of further bone loss
• With current or history of breast cancer or other hormone-sensitive malignancies, and with increased risk for hormone-sensitive malignancies
• With known hepatic impairment or disease
• With undiagnosed abnormal uterine bleeding
• With known anaphylactic reaction, angioedema, or hypersensitivity to Myfembree or any of its components. Anaphylactoid reactions have been reported.

Orilissa has the following contraindications:(1)

• Pregnancy
• Known osteoporosis
• Severe hepatic impairment
• Organic anion transporting polypeptide (OATP) 1B1 inhibitors that significantly increase elagolix plasma concentrations
• Hypersensitivity reactions

Oriahnn has the following boxed warnings:(2)

• Estrogen and progestin combinations, including Oriahnn, increase the risk of thrombotic or thromboembolic disorders including pulmonary embolism, deep vein thrombosis, stroke and myocardial infarction, especially in patients at increased risk for these events.
• Oriahnn is contraindicated in patients with current or a history of thrombotic or thromboembolic disorders and in patients at increased risk for these events, including patients over 35 years of age who smoke and patients with uncontrolled hypertension.

Oriahnn is contraindicated in patients:(2)

• With a high risk of arterial, venous thrombotic, or thromboembolic disorders. Examples include patients over 35 years of age who smoke, and patients who are known to have: 
  • current or history of deep vein thrombosis or pulmonary embolism 
  • vascular disease (e.g., cerebrovascular disease, coronary artery disease, peripheral vascular disease) 
  • thrombogenic valvular or thrombogenic rhythm diseases of the heart (for example, subacute bacterial endocarditis with valvular disease, or atrial fibrillation)
  • inherited or acquired hypercoagulopathies 
  • uncontrolled hypertension
  • headaches with focal neurological symptoms or have migraine headaches with aura if over age 35
• Who are pregnant. Exposure to Oriahnn early in pregnancy may increase the risk of early pregnancy loss
• With known osteoporosis because of the risk of further bone loss
• With current or history of breast cancer or other hormonally-sensitive malignancies, and with increased risk for hormonally-sensitive malignancies
• With known hepatic impairment or disease
• With undiagnosed abnormal uterine bleeding
• With known anaphylactic reaction, angioedema, or hypersensitivity to Oriahnn or any of its components
• Taking inhibitors of organic anion transporting polypeptide (OATP)1B1 (a hepatic uptake transporter) that are known or expected to significantly increase elagolix plasma concentrations

Elagolix causes a dose-dependent decrease in bone mineral density (BMD). BMD is greater with increasing duration of use and may not be completely reversible after stopping treatment. The impact of these BMD decreases on long-term bone health and future fracture risk are unknown. Consider assessment of BMD in patients with a history of a low-trauma fracture or other risk factors for osteoporosis or bone loss, and do not use in patients with known osteoporosis.(1)

1

Orilissa prescribing information. AbbVie Inc. June 2023.

2

Oriahnn prescribing information. AbbVie Inc. June 2023.

3

Myfembree prescribing information. Myovant Sciences, Inc. April 2024.

4

Vercellini P, Viganò P, Somigliana E, Fedele L. Endometriosis: pathogenesis and treatment. Nat Rev Endocrinol 2014; 10:261.

5

American College of Obstetricians and Gynecologists. ACOG practice bulletin no. 114: management of endometriosis. Obstet Gynecol 2010; 116:223. Reaffirmed 2018.

6

Sabry, M., & Al-Hendy, A. (2012). Medical treatment of uterine leiomyoma. Reproductive sciences (Thousand Oaks, Calif.), 19(4), 339–353. https://doi.org/10.1177/1933719111432867.

7

Munro MG, Critchley HO, Fraser IS, FIGO Menstrual Disorders Working Group. The FIGO classification of causes of abnormal uterine bleeding in the reproductive years. Fertil Steril 2011; 95:2204.

8

American College of Obstetricians and Gynecologists. ACOG practice bulletin no. 128: diagnosis of abnormal uterine bleeding in reproductive-aged women. Obstet Gynecol. 2012;120(1):197-206. Reaffirmed 2016. doi:10.1097/AOG.0b013e318262e320.

9

 American College of Obstetricians and Gynecologists Committee on Practice Bulletins–Gynecology. Management of Symptomatic Uterine Leiomyomas: ACOG Practice Bulletin, Number 228. Obstet Gynecol. 2021;137(6):e100-e115. 

10

Schlaff WD, Ackerman RT, Al-Hendy A, et al. Elagolix for Heavy Menstrual Bleeding in Women with Uterine Fibroids. N Engl J Med 2020; 382:328-340.

11

Taylor HS, Giudice LC, Lessey BA, et al. Treatment of Endometriosis-Associated Pain with Elagolix, an Oral GnRH Antagonist. N Engl J Med 2017; 377:28.

12

Becker CM, Bokor A, et al. ESHRE Endometriosis Guideline Group. ESHRE guideline: endometriosis. Hum Reprod Open. 2022 Feb 26;2022(2):hoac009. doi: 10.1093/hropen/hoac009. 

Orilissa

elagolix sodium tab

150 MG ; 200 MG

M ; N ; O ; Y

N

Oriahnn

elagolix-estrad-noreth

300-1-0.5 & 300 MG

M ; N ; O ; Y

N

Myfembree

relugolix-estradiol-norethindrone acetate tab

40-1-0.5 MG

M ; N ; O ; Y

N

Myfembree

Relugolix-Estradiol-Norethindrone Acetate Tab

40-1-0.5 MG

30

Tablets

30

DAYS

Oriahnn

Elagolix-Estrad-Noreth 300-1-0.5MG & Elagolix 300MG Cap Pack

300-1-0.5 & 300 MG

56

Capsules

28

DAYS

Orilissa

Elagolix Sodium Tab 150 MG (Base Equiv)

150 MG

30

Tablets

30

DAYS

Orilissa

Elagolix Sodium Tab 200 MG (Base Equiv)

200 MG

60

Tablets

30

DAYS

Myfembree

relugolix-estradiol-norethindrone acetate tab

40-1-0.5 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Oriahnn

elagolix-estrad-noreth

300-1-0.5 & 300 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Orilissa

elagolix sodium tab

150 MG ; 200 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Myfembree

Relugolix-Estradiol-Norethindrone Acetate Tab

40-1-0.5 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Oriahnn

Elagolix-Estrad-Noreth 300-1-0.5MG & Elagolix 300MG Cap Pack

300-1-0.5 & 300 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Orilissa

Elagolix Sodium Tab 150 MG (Base Equiv)

150 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Orilissa

Elagolix Sodium Tab 200 MG (Base Equiv)

200 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Myfembree

Initial Evaluation

Target Agent(s) will be approved when ALL of the following are met:

1. ONE of the following:
   1. The patient has a diagnosis of heavy menstrual bleeding associated with uterine leiomyomas (fibroids) and BOTH of the following:
      1. The patient’s diagnosis of uterine fibroids was confirmed via imaging (e.g., ultrasound) AND
      2. The patient has NOT had a hysterectomy OR
   2. The patient has a diagnosis of moderate to severe pain associated with endometriosis AND
2. The patient is premenopausal (e.g., less than 12 months since last menstrual period) AND
3. The patient’s bone health has been assessed AND allows for initiating therapy with the requested agent AND
4. ONE of the following:
   1. The patient has tried and had an inadequate response to ONE prerequisite agent (e.g., hormonal contraceptive, NSAID, COX-II inhibitor) used in the treatment of the requested indication OR
   2. The patient has an intolerance or hypersensitivity to ONE prerequisite agent (e.g., hormonal contraceptive, NSAID, COX-II inhibitor) used in the treatment of the requested indication OR
   3. The patient has an FDA labeled contraindication to ALL prerequisite therapies (hormonal contraceptives [i.e., oral, topical patches, implants, injections, IUD], NSAIDs, COX-II inhibitors) used in the treatment of the requested indication AND
5. The patient will NOT be using the requested agent in combination with another GnRH antagonist agent targeted in this program (e.g., elagolix, relugolix) for the requested indication AND
6. The patient does NOT have any FDA labeled contraindications to the requested agent AND
7. ONE of the following:
   1. The patient is initiating therapy with the requested agent OR
   2. The patient is not initiating therapy with the requested agent and BOTH of the following:
      1. There is support confirming the number of months the patient has been on therapy AND
      2. The total duration of treatment with the requested agent has NOT exceeded 24 months per lifetime

Length of Approval: up to 6 months, with a lifetime maximum of 24 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

*Step therapy requirement may not apply if a prior health plan paid for the medication - documentation of a paid claim may be required.

Renewal Evaluation

Target Agent(s) will be approved when ALL of the following are met:

1. The patient has been previously approved for the requested agent through the plan’s Prior Authorization process [Note: patients not previously approved for the requested agent will require initial evaluation review] AND
2. The patient is premenopausal (e.g., less than 12 months since last menstrual period) AND
3. The patient has had clinical benefit with the requested agent AND
4. The patient’s bone health has been assessed AND allows for continued therapy with the requested agent AND
5. The patient has NOT had a fragility fracture since starting therapy with the requested agent AND
6. The patient will NOT be using the requested agent in combination with another GnRH antagonist agent targeted in this program (e.g., elagolix, relugolix) for the requested indication AND
7. The patient does NOT have any FDA labeled contraindications to the requested agent AND
8. BOTH of the following:
   1. There is support confirming the number of months the patient has been on therapy AND
   2. The total duration of treatment with the requested agent has NOT exceeded 24 months per lifetime

Length of Approval: up to 6 months, with a lifetime maximum of 24 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

Oriahnn

Initial Evaluation

Target Agent(s) will be approved when ALL of the following are met:

1. The patient has a diagnosis of heavy menstrual bleeding associated with uterine leiomyomas (fibroids) AND
2. The patient’s diagnosis of uterine fibroids was confirmed via imaging (e.g., ultrasound) AND
3. The patient has NOT had a hysterectomy AND
4. The patient is premenopausal (e.g., less than 12 months since last menstrual period) AND
5. The patient’s bone health has been assessed AND allows for initiating therapy with the requested agent AND
6. ONE of the following:
   1. The patient has tried and had an inadequate response to ONE prerequisite agent (e.g., hormonal contraceptive, NSAID, COX-II inhibitor) used in the treatment of the requested indication OR
   2. The patient has an intolerance or hypersensitivity to ONE prerequisite agent (e.g., hormonal contraceptive, NSAID, COX-II inhibitor) used in the treatment of the requested indication OR
   3. The patient has an FDA labeled contraindication to ALL prerequisite therapies (hormonal contraceptives [i.e., oral, topical patches, implants, injections, IUD], NSAIDs, COX-II inhibitors) used in the treatment of the requested indication AND
7. The patient will NOT be using the requested agent in combination with another GnRH antagonist agent targeted in this program (e.g., elagolix, relugolix) for the requested indication AND
8. The patient does NOT have any FDA labeled contraindications to the requested agent AND
9. ONE of the following:
   1. The patient is initiating therapy with the requested agent OR
   2. The patient is not initiating therapy with the requested agent and BOTH of the following:
      1. There is support confirming the number of months the patient has been on therapy AND
      2. The total duration of treatment with the requested agent has NOT exceeded 24 months per lifetime

Length of Approval: up to 6 months, with a lifetime maximum of 24 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

*Step therapy requirement may not apply if a prior health plan paid for the medication - documentation of a paid claim may be required.

Renewal Evaluation

Target Agent(s) will be approved when ALL of the following are met:

1. The patient has been previously approved for the requested agent through the plan’s Prior Authorization process [Note: patients not previously approved for the requested agent will require initial evaluation review] AND
2. The patient is premenopausal (e.g., less than 12 months since last menstrual period) AND
3. The patient has had clinical benefit with the requested agent AND
4. The patient’s bone health has been assessed AND allows for continued therapy with the requested agent AND
5. The patient has NOT had a fragility fracture since starting therapy with the requested agent AND
6. The patient will NOT be using the requested agent in combination with another GnRH antagonist agent targeted in this program (e.g., elagolix, relugolix) for the requested indication AND
7. The patient does NOT have any FDA labeled contraindications to the requested agent AND
8. BOTH of the following:
   1. There is support confirming the number of months the patient has been on therapy AND
   2. The total duration of treatment with the requested agent has NOT exceeded 24 months per lifetime

Length of Approval: up to 6 months, with a lifetime maximum of 24 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

Orilissa

Initial Evaluation

Target Agent(s) will be approved when ALL of the following are met:

1. The patient has a diagnosis of moderate to severe pain associated with endometriosis AND
2. The patient is premenopausal (e.g., less than 12 months since last menstrual period) AND
3. ONE of the following:
   1. The patient has tried and had an inadequate response to ONE prerequisite agent (e.g., hormonal contraceptive, NSAID, COX-II inhibitor) used in the treatment of the requested indication OR
   2. The patient has an intolerance or hypersensitivity to ONE prerequisite agent (e.g., hormonal contraceptive, NSAID, COX-II inhibitor) used in the treatment of the requested indication OR
   3. The patient has an FDA labeled contraindication to ALL prerequisite therapies (hormonal contraceptives [i.e., oral, topical patches, implants, injections, IUD], NSAIDs, COX-II inhibitors) used in the treatment of the requested indication AND
4. The patient’s bone health has been assessed AND allows for initiating therapy with the requested agent AND​​​
5. The patient will NOT be using the requested agent in combination with another GnRH antagonist agent targeted in this program (e.g., elagolix, relugolix) for the requested indication AND
6. The patient does NOT have any FDA labeled contraindications to the requested agent AND
7. ONE of the following:
   1. The patient does NOT have coexisting moderate hepatic impairment (Child-Pugh [CP]/ Child-Turcotte-Pugh [CTP] Class B) AND ONE of the following:
      1. The patient is initiating therapy with the requested agent and strength OR
      2. The patient is not initiating therapy with the requested agent and strength and BOTH of the following:
         1. There is support confirming the number of months the patient has been on therapy AND
         2. ONE of the following:
            1. The requested strength is 150 mg AND the total duration of treatment with the requested strength has NOT exceeded 24 months per lifetime OR
            2. The requested strength is 200 mg AND the total duration of treatment with the requested strength has NOT exceeded 6 months per lifetime OR
   2. The patient does have coexisting moderate hepatic impairment (Child-Pugh [CP]/ Child-Turcotte-Pugh [CTP] Class B) AND BOTH of the following:
      1. The requested strength is 150 mg AND
      2. ONE of the following:
         1. The patient is initiating therapy with the requested agent and strength OR
         2. The patient is not initiating therapy with the requested agent and strength AND BOTH of the following:
            1. There is support confirming the number of months the patient has been on therapy AND
            2. The total duration of treatment with the requested strength has NOT exceeded 6 months per lifetime

Length of Approval: up to 6 months with a lifetime maximum of 24 months with the 150 mg without coexisting moderate hepatic impairment; up to 6 months with a lifetime maximum of 6 months with the 150 mg with coexisting moderate hepatic impairment; up to 6 months with a lifetime maximum of 6 months with the 200 mg

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

*Step therapy requirement may not apply if a prior health plan paid for the medication - documentation of a paid claim may be required.

Renewal Evaluation

Target Agent(s) will be approved when ALL of the following are met:

1. The patient has been previously approved for the requested agent through the plan’s Prior Authorization process (*please note requests for 200 mg strength should always be reviewed under initial criteria) [Note: patients not previously approved for the requested agent will require initial evaluation review] AND
2. The patient is premenopausal (e.g., less than 12 months since last menstrual period) AND
3. The patient has had clinical benefit with the requested agent AND
4. The patient’s bone health has been assessed AND allows for continued therapy with the requested agent AND
5. The patient has NOT had a fragility fracture since starting therapy with the requested agent AND
6. The patient will NOT be using the requested agent in combination with another GnRH antagonist agent targeted in this program (e.g., elagolix, relugolix) for the requested indication AND
7. The patient does NOT have any FDA labeled contraindications to the requested agent AND
8. BOTH of the following:
   1. There is support confirming the number of months the patient has been on therapy with the requested agent and strength AND
   2. ONE of the following:
      1. The patient does NOT have coexisting moderate hepatic impairment (Child-Pugh [CP]/ Child-Turcotte-Pugh [CTP] Class B) AND the total duration of treatment with the requested strength has NOT exceeded 24 months per lifetime OR
      2. The patient does have coexisting moderate hepatic impairment (Child-Pugh [CP]/ Child-Turcotte-Pugh [CTP] Class B) AND the total duration of treatment with the requested strength has NOT exceeded 6 months per lifetime

Length of Approval: up to 6 months with a lifetime maximum of 24 months with the 150 mg without coexisting moderate hepatic impairment; up to 6 months with a lifetime maximum of 6 months with the 150 mg with coexisting moderate hepatic impairment

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

QL with PA

Quantity limit for the Target Agent(s) will be approved when the following is met:

1. The requested quantity (dose) does NOT exceed the program quantity limit

Length of Approval: Myfembree and Oriahnn: up to 6 months with a lifetime maximum of 24 months.

Orilissa: up to 6 months with a lifetime maximum of 24 months with the 150 mg without coexisting moderate hepatic impairment; up to 6 months with a lifetime maximum of 6 months with the 150 mg with coexisting moderate hepatic impairment; up to 6 months with a lifetime maximum of 6 months with the 200 mg