Commercial

Medical Policy

Notification

Gonadotropin-Releasing Hormone Agonist (Camcevi™, Eligard®, Fensolvi®, Lupron Depot®)

Notification Issued Date:

This version of the policy will become effective 03/08/2021.

This policy has been updated to communicate the coverage position of leuprolide acetate (Fensolvi), represented by HCPCS J1950. Additionally, the medical necessity criteria have been revised to reflect the updated coverage position from the National Comprehensive Cancer Network (NCCN) for endometriosis, head and neck cancers, ovarian cancer, and prostate cancer.

Title:

Gonadotropin-Releasing Hormone Agonist (Camcevi™, Eligard®, Fensolvi®, Lupron Depot®)

Policy #:

08.01.33i

Policy

The Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition.

MEDICALLY NECESSARY

COMPANY-DESIGNATED PREFERRED PRODUCTS

Although there are many leuprolide products on the market (e.g., Camcevi, Eligard, Lupron Depot), there is no reliable evidence of the superiority of any one product of leuprolide compared with other products. Although Lupron Depot (leuprolide acetate) and Camcevi (leuprolide mesylate) have been approved by the U.S. Food and Drug Administration (FDA) for prostate cancer, and Company-recognized Drug Compendia support the use of these for certain cancers, leuprolide acetate (Eligard and Lupron Depot 7.5 mg, represented by Healthcare Common Procedure Coding System [HCPCS] J9217) are considered to be the lower cost alternative. The Company has designated leuprolide acetate (Eligard and Lupron Depot 7.5 mg, represented by HCPCS J9217) as its preferred products for the following indications:

Prostate cancer
Salivary gland tumors

These products are less costly and at least as likely to produce equivalent therapeutic results as the nonpreferred leuprolide products, which include but are not limited to Camcevi (represented by HCPCS J1952), Lupron Depot (represented by HCPCS J1950), and any other nonpreferred leuprolide products.

NOTE: All other uses described in this policy as Medically Necessary are eligible for coverage and are not subject to the Company-designated Preferred Product requirement.

NONPREFERRED PRODUCTS

Use of the nonpreferred leuprolide products, which include, but are not limited to, Camcevi (represented by HCPCS J1952), Lupron Depot (represented by HCPCS J1950), and any other nonpreferred leuprolide product is considered medically necessary and, therefore, covered only for individuals who are currently receiving or have previously received a nonpreferred product for the specified leuprolide indication.

If the individual has not previously received leuprolide to treat the specified indication, these nonpreferred products are only eligible for coverage when the individual has contraindication(s) or intolerance(s) to the Company-designated preferred product, leuprolide acetate (Eligard and Lupron Depot 7.5 mg, represented by HCPCS J9217).

MEDICALLY NECESSARY INDICATIONS

Leuprolide acetate/mesylate for injection is considered medically necessary and, therefore, covered when the following criteria are met:

Breast Cancer
Leuprolide acetate for injection is considered medically necessary and, therefore, covered for:

Invasive or inflammatory breast cancer treatment in premenopausal females* with hormone receptor–positive breast cancer in combination with any of the following:
- Adjuvant endocrine therapy
- Endocrine therapy for recurrent unresectable (local or regional) or stage IV (M1) disease

Central Precocious Puberty

Leuprolide acetate for injection is considered medically necessary and, therefore, covered for children with a clinical diagnosis of central precocious puberty confirmed by all of the following criteria:

An increased pubertal luteinizing hormone response to a GnRH stimulation test
A bone age greater than at least 1 year compared to chronological age

Endometriosis

Leuprolide acetate for injection is considered medically necessary and, therefore, covered for a maximum of 6 months for initial treatment and a maximum of 6 months for retreatment (total 12 months) for the following:

Management of endometriosis, including pain relief and reduction of endometriotic lesions
Initial management of endometriosis and for management of recurrence of symptoms with norethindrone acetate, 5 mg daily

Head and Neck Cancers

Salivary Gland Tumors
Leuprolide acetate for injection is considered medically necessary and, therefore, covered as a single agent for the treatment of androgen receptor–positive recurrent disease with either of the following:

Distant metastases in individuals with a performance status (PS) of 0–3
Unresectable locoregional recurrence or second primary with prior radiation therapy

Gender Dysphoria: Male-to-female

Leuprolide acetate for injection is considered medically necessary and, therefore, covered for puberty suppression when all of the following criteria are met:

The adolescent has demonstrated a long-lasting and intense pattern of gender nonconformity or gender dysphoria (whether suppressed or expressed), in accordance with criteria established in the Diagnostic and Statistical Manual of Mental Disorders - Fifth Edition [DSM-5].

Gender dysphoria emerged or worsened with the onset of puberty.

The individual has reached at least Tanner stage 2 of development.

Ovarian Cancer/Fallopian Tube Cancer/Primary Peritoneal Cancer

Leuprolide acetate for injection is considered medically necessary and, therefore, covered for hormone therapy as a single agent for persistent disease or recurrence of ovarian cancer/fallopian tube cancer/primary peritoneal cancer (endometrioid, serous), carcinosarcoma (malignant mixed Mullerian tumors), clear cell carcinoma of the ovary, grade 1 endometrioid carcinoma, mucinous carcinoma of the ovary when one of the following criteria are met:

For progression on primary, maintenance, or recurrence therapy (platinum-resistant disease)

For stable or persistent disease (if not on maintenance therapy) (platinum-resistant disease)

For complete remission and relapse less than 6 months after completing chemotherapy (platinum-resistant disease)

For radiographic and/or clinical relapse in individuals with previous complete remission and relapse 6 months or longer after completing prior chemotherapy (platinum-sensitive disease)
As a single agent for clinical relapse in individuals with stage II–IV granulosa-cell tumors
Hormone therapy for low-grade serous carcinoma (serous, borderline epithelial), as a single agent for platinum-sensitive or platinum-resistant recurrence (if an aromatase inhibitor was given previously)

Prostate Cancer

Leuprolide acetate/mesylate for injection is considered medically necessary and, therefore, covered for:

Treatment (including palliative treatment) for individuals with advanced prostate cancer
Adjuvant androgen deprivation therapy (ADT) as a single agent or in combination with a first-generation antiandrogen, with external beam radiation therapy (EBRT) if adverse features (i.e., positive margins, seminal vesicle invasion, extracapsular extension, or detectable prostate-specific antigen [PSA]) noted after radical prostatectomy (RP) for individuals:

In the very low risk group^† and greater than 20-year expected survival
In the low-risk group^† and 10 year or greater expected survival
With or without pelvic lymph node dissection (PLND) and no lymph node metastases in the favorable or unfavorable intermediate-risk group^† and greater than 10-year expected survival
With PLND and no lymph node metastases in the high- or very-high-risk group^† or regional risk group (any T, N1, M0) and greater than 5-year expected survival or symptomatic

Adjuvant ADT as a single agent or in combination with a first-generation antiandrogen, without EBRT if lymph node metastasis found during PLND for individuals:

In the favorable or unfavorable intermediate risk group^† and greater than 10-year expected survival
In the high or very high risk groups^† and greater than 5-year expected survival or symptomatic
In the regional risk group (any T, N1, M0) and greater than 5-year expected survival or symptomatic

ADT as:

A single agent if life expectancy 5 years or less and symptomatic, in individuals with very low, low, and intermediate risk disease^†
As a single agent if life expectancy 5 years or less and asymptomatic, in individuals with high risk^† or very high risk^† disease in which complications such as hydronephrosis or metastasis can be expected within 5 years
A single agent (with or without EBRT), in combination with first-generation antiandrogen (with or without EBRT), or in combination with either abiraterone (National Comprehensive Cancer Network [NCCN] preferred with EBRT) excluding fine particle formulation with concurrent steroids (prednisone or methylprednisolone) in individuals with regional risk disease (any T, N1, M0) and life expectancy greater than 5 years or symptomatic
As a single agent for individuals in the regional risk group (Any T, N1, M0) and life expectancy 5 years or less and asymptomatic

ADT as a single agent or in combination with a first-generation antiandrogen for:

M0 PSA) persistence/recurrence after radical prostatectomy in combination with EBRT if studies negative for distant metastatic disease and pelvic recurrence or imaging not performed and life expectancy greater than 5 years (NCCN-preferred regimen)
For M0 PSA persistence/recurrence after radical prostatectomy in combination with EBRT with or without abiraterone (excluding fine-particle formulation) with concurrent steroids (prednisone or methylprednisolone) if studies are positive for pelvic recurrence and life expectancy greater than 5 years
M0 PSA persistence/recurrence or positive digital rectal examination (DRE) after EBRT if biopsy negative or not performed, and studies negative for distant metastatic disease and life expectancy greater than 5 years
M0 PSA recurrence or positive DRE after EBRT if studies positive for pelvic recurrence and life expectancy greater than 5 years

Initial ADT with EBRT as a single agent or in combination with a first-generation antiandrogen if life expectancy greater than 5 years or symptomatic:
- For 4–6 months with or without brachytherapy for individuals in the unfavorable intermediate risk group^†
- For 1.5–3 years for individuals in the high or very high risk group^†
- For 2 years of ADT in combination with abiraterone for individuals in the very high risk group^† only
- For 1–3 years with brachytherapy for individuals in the high or very high risk group^†
- For individuals in the regional risk group (any T, N1, M0) as a single agent, in combination with a first generation antiandrogen, or in combination with abiraterone with concurrent steroid (prednisone or methylprednisolone) (NCCN-preferred regimen)
Single-agent treatment for individuals who progressed on observation of localized disease
For castration-sensitive disease

As a single agent for M0 or M1 disease (note per NCCN: a first-generation antiandrogen must be given for 7 days or greater to prevent testosterone flare if metastases are present in weight-bearing bone)
In combination with a first-generation antiandrogen for M0 or M1 disease
In combination with docetaxel plus abiraterone (excluding fine-particle formulation) with concurrent steroids (prednisone or methylprednisolone) or darolutamide (both NCCN-preferred regimens)
In combination with either apalutamide or enzalutamide for M1 disease (both NCCN-preferred regimens)
In combination with abiraterone (excluding fine-particle formulation) and prednisone for M1 disease (NCCN-preferred regimen)
As a single agent or in combination with a first-generation antiandrogen and EBRT to the primary tumor for low-metastatic burden M1 disease

For M0 or M1 castration-resistant disease as ADT to maintain castrate levels of serum testosterone (<50 ng/dL)

* Men with breast cancer should be treated similarly to postmenopausal women, except that use of an aromatase inhibitor is ineffective without concomitant suppression of testicular steroidogenesis.

^†According to National Comprehensive Cancer Network guidelines:

Very low risk refers to individuals with clinical stage T1c, Grade Group 1, PSA less than 10 ng/mL, fewer than three prostate biopsy fragments/cores positive with 50% or less cancer in each fragment/core, and PSA density less than 0.15 mg/mL/g.
Low risk refers to individuals with clinical stage T1 to T2a, Grade Group 1, and PSA less than 10 ng/mL.
intermediate risk refers to individuals
- Who have no high- or very-high-risk features and has one or more intermediate risk factors (IRF):
  - Clinical stage T2b to T2c
  - Grade Group 2 or 3
  - PSA 10 ng/mL to 20 ng/mL
- Favorable intermediate risk refers to individuals with 1 IRF, Grade Group 1 or 2, and <50% biopsy cores positive
- Unfavorable intermediate risk refers to individuals with 2 or 3 IRFs, and/or Grade Group 3, and/or 50% or more biopsy cores positive
High risk refers to individuals who have no very-high-risk features and have at least one high-risk feature:

Clinical stage T3a, Grade Group 4 or 5, or PSA greater than 20 ng/mL

Very high-risk refers to individuals with clinical stage T3b to T4 , or primary Gleason pattern 5, or 2–3 high-risk features, or more than 4 biopsy cores with grade Group 4 or 5

Uterine Leiomyomata (Uterine Fibroids)

Leuprolide acetate for injection is considered medically necessary and, therefore, covered for the preoperative hematologic improvement of individuals with anemia caused by uterine leiomyomata concomitantly with iron therapy. According to the FDA-approved label, duration of therapy should be limited to up to 3 months.

NOT MEDICALLY NECESSARY 

The Company's products contain a definition of medical necessity that includes a requirement that a service not be more costly than an alternative service that is at least as likely to produce equivalent therapeutic or diagnostic results for the treatment of an individual's illness.

Although Lupron Depot (leuprolide acetate) has been approved by the FDA for prostate cancer and Compendia support the use of Lupron Depot for multiple types of cancers, Eligard (leuprolide acetate) is considered to be the lower cost alternative.

For individuals receiving their first course of leuprolide for the following indications, use of Lupron Depot (represented by HCPCS J1950) is considered not medically necessary and, therefore, not covered for the following indications because they are more costly than the preferred product that is at least as likely to produce equivalent therapeutic results for that individual's condition.

Prostate cancer
Salivary gland tumors

For individuals receiving their first course of leuprolide for the following indications, use of leuprolide acetate (Fensolvi, represented by HCPCS J1951) is considered not medically necessary and, therefore, not covered for the following indications because it is more costly than the preferred products and at least as likely to produce equivalent therapeutic results for that individual's condition.

Breast cancer

Endometriosis

Gender dysphoria

Ovarian cancer/fallopian tube cancer/primary peritoneal cancer

Prostate cancer

Salivary gland tumors

Uterine leiomyomata (uterine fibroids)

For individuals receiving their first course of leuprolide for the following indications, use of leuprolide mesylate (Camcevi, represented by HCPCS J1952) is considered not medically necessary and, therefore, not covered for the following indications because it is more costly than the preferred products and at least as likely to produce equivalent therapeutic results for that individual's condition.

Breast cancer

Central precocious puberty

Endometriosis

Gender dysphoria

Ovarian cancer/fallopian tube cancer/primary peritoneal cancer

Prostate cancer

Salivary gland tumors

Uterine leiomyomata (uterine fibroids)

EXPERIMENTAL/INVESTIGATIONAL

All other uses for gonadotropin-releasing hormone agonist (Camcevi, Eligard, Fensolvi, Lupron Depot) are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the Company medical policy on off-label coverage for prescription drugs and biologics.

MANDATES

PENNSYLVANIA MEMBERS
In accordance with the Commonwealth of Pennsylvania's Act 6 of 2020 or Fair Access to Cancer Treatment Act, for members who are enrolled in Pennsylvania commercial products who have stage 4, advanced metastatic cancer, refer to the Medical Policy titled "Coverage of Anticancer Prescription Oral and Injectable Drugs and Biologics and Supportive Agents" (08.01.08) for additional information regarding the applicable coverage of drugs and biologics.

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the drug.

Guidelines

GLEASON SCORE

The Gleason Score is a grading system for prostate cancer tissue. This score is determined by characterizing the prostate cancer cells on a grade scale of 1 (most differentiated) to 5 (least differentiated) based on the appearance under a microscope. The two most prevalent grades are added up to equal the Gleason score. Generally prostate cancer with a Gleason score of 2–4 is considered well-differentiated or low grade; Gleason score 5–7 is considered moderately differentiated; Gleason score 8–10 is considered poorly differentiated or high grade.

GRADE GROUP

A revised grading system for prostate cancer tissue was created at the 2014 International Society of Urological Pathology Consensus Conference, which further assigns Grade Groups, derived from the Gleason Score.

Grade Group	Gleason Score	Gleason Pattern
1	≤ 6	≤ 3 + 3
2	7	3 + 4
3	7	4 + 3
4	8	4 + 4, 3 + 5, 5 + 3
5	9 or 10	4 + 5, 5 + 4, 5 + 5

TANNER SCALE

Tanner score is a scale of progression through puberty. Males are rated for genital development and pubic hair growth. Females are rated for breast development and pubic hair growth. Males and females are categorized into one of five stages: Stage 1 (preadolescent) to Stage 5 (adult).

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, gonadotropin-releasing hormone agonist (Camcevi, Eligard, Fensolvi, Lupron Depot) is covered under the medical benefits of the Company’s products when the medical necessity criteria listed in this medical policy are met.

However, drugs that are identified in this policy with uses that are considered not medically necessary are not eligible for coverage or reimbursement by the Company.

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

Leuprolide acetate (Eligard) for injection, 7.5 mg for 1-month administration, 22.5 mg for a 3-month administration, 30 mg for 4-month administration, and 45 mg for 6-month administration was approved by the FDA in January 2002 for palliative treatment of advanced prostate cancer. In July 2023, the prescribing information was revised from "palliative treatment" to "treatment" of advanced prostatic cancer. The safety and effectiveness of leuprolide acetate (Eligard) for injection in pediatric individuals have not been established.

Leuprolide acetate (Fensolvi) for injection, 45 mg for 6-month administration, was approved by the FDA on May 1, 2020, for treatment of children with central precocious puberty. The safety and effectiveness in pediatric individuals below the age of 2 years have not been established; therefore, its use in children under 2 years is not recommended.

Leuprolide acetate (Lupron Depot) for injection, 7.5 mg for 1-month administration, 22.5 mg for a 3-month administration, 30 mg for 4-month administration, and 45 mg for 6-month administration was approved by the FDA on January 1989 for palliative treatment of advanced prostate cancer. In 2022, the prescribing information for was revised from "palliative treatment" to "treatment" of advanced prostatic cancer.

Leuprolide acetate (Lupron Depot) for injection, 3.75 mg for 1-month administration and 11.25 mg for 3-month administration, was approved by the FDA on October 1990 for:

Management of endometriosis, including pain relief and reduction of endometriotic lesions
Preoperative hematologic improvement of individuals with anemia caused by uterine leiomyomata

Leuprolide acetate (Lupron Depot-PED) for injection was approved by the FDA on April 1993 for treatment of children with central precocious puberty. The safety and effectiveness in pediatric individuals below the age of 1 year have not been established; therefore, its use in children under 1 year is not recommended.

Leuprolide mesylate injectable emulsion, for subcutaneous use (Camcevi), 42 mg for a 6-month administration, was approved by the FDA on May 25, 2021, for treatment of adults with advanced prostate cancer. The safety and effectiveness in pediatric individuals have not been established.

Description

Gonadotropin-releasing hormone (GnRH) analogue is a 10-amino-acid peptide that stimulates the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). GnRH directly increases its own receptor number by pulsatile secretion. GnRH analogues have a greater potency than the natural hormone and have a longer half-life. Initially, GnRH analogues stimulate the secretion of FSH and LH. With a continued secretion of GnRH analogues there is a decrease in the GnRH receptors leading to a decrease in FSH and LH secretion.

CAMCEVI

On May 25, 2021, leuprolide injectable emulsion for subcutaneous use (Camcevi) was approved by the US Food and Drug Administration (FDA) for the treatment of adults with advanced prostate cancer. It is administered subcutaneously 42 mg every 6 months.

ELIGARD

In January 2002, leuprolide acetate (Eligard) was FDA-approved for palliative treatment of advanced prostate cancer. Leuprolide acetate (Eligard) is administered subcutaneously 7.5 mg every month, 22.5 mg every 3 months, 30 mg every 4 months, or 45 mg every 6 months. In July 2023, the prescribing information for leuprolide acetate (Eligard) was revised from the palliative treatment of advanced prostatic cancer to the treatment of advanced prostatic cancer.

FENSOLVI

On May 1, 2020, leuprolide acetate (Fensolvi) for injection was approved by the FDA for treatment of children with central precocious puberty. Leuprolide acetate (Fensolvi) is administered subcutaneously 45 mg every 6 months.

LUPRON DEPOT

Leuprolide acetate (Lupron Depot) is a synthetic nonapeptide analogue of the naturally occurring GnRH. The continuous administration results in suppression of ovarian and testicular steroidogenesis. Leuprolide acetate (Lupron Depot), 7.5 mg for 1-month administration, was approved by the FDA in January 1989 for palliative treatment of advanced palliative prostatic cancer. Three additional doses of leuprolide acetate (Lupron Depot) were approved: 22.5 mg for a 3-month administration (in January 1996), 30 mg for 4-month administration (in July 1997), and 45 mg for 6-month administration (in June 2011). In 2022, the prescribing information for leuprolide acetate (Lupron Depot) was revised from the palliative treatment of advanced prostatic cancer to the treatment of advanced prostatic cancer. Leuprolide acetate (Lupron Depot), 3.75 mg for 1-month administration, was approved by the FDA for management of endometriosis, including pain relief and reduction of endometriotic lesions. Leuprolide acetate (Lupron Depot) given monthly with norethindrone acetate 5 mg daily is also indicated for initial management of endometriosis and for management of recurrence of symptoms. According to the FDA- approved label, initial treatment or retreatment should be limited to 6 months. Leuprolide acetate (Lupron Depot) was also FDA-approved for preoperative hematologic improvement of individuals with anemia caused by uterine leiomyomata (uterine leiomyoma or uterine fibroid) when used with iron therapy. According to the FDA-approved label, the recommended duration of therapy is up to 3 months. A dosage of 11.25 mg every 3 months can also be administered for endometriosis and uterine leiomyomata.

In 1993, leuprolide acetate (Lupron Depot-PED) was FDA approved for the treatment of children with central precocious puberty. The dosage is 7.5 mg, 11.25 mg, or 15 mg for 1-month administration, based on the child’s weight, or 11.25 mg or 30 mg for 3-month administration, or 45 mg for 6-month administration. Central precocious puberty is defined as early onset of secondary sexual characteristics (generally before the age of 8 for girls and before the age of 9 for boys) associated with pubertal pituitary gonadotropin activation. This condition can result in significantly advanced bone age and diminished adult height. Leuprolide acetate (Lupron Depot-PED) treatment should be discontinued at the appropriate age of onset of puberty at the discretion of the professional provider.

OFF-LABEL INDICATIONS

There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company’s off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.

References

American Hospital Formulary Services (AHFS) Drug Information 2023. Leuprolide Acetate. [Lexi-Comp website]. 01/11/2021. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed August 15, 2023.

American Association of Gynecologic Laparoscopists (AAGL): Advancing minimally invasive gynecology worldwide. AAGL Practice Report: Practice guidelines for the diagnosis and management of submucous leiomyomas. J Minim Invasive Gynecol. 2012;19(2):152-171.

Burstein H, Lacchetti C, Anderson H, et al. Adjuvant endocrine therapy for women with hormone receptor-positive breast cancer: American Society of Clinical Oncology Clinical Practice Guideline update on ovarian suppression. J Clin Oncol. 2016;34(14):1689-1701.

Camcevi (leuprolide) injectable emulsion, for subcutaneous use. Accord BioPharma Inc.; Durham, NC. 05/2021. Available at: https://www.camcevi.com/. Accessed August 10, 2023.

Clowse M, Behera M, Anders C, et. al. Ovarian preservation of GnRH agonists during chemotherapy: a meta-analysis. J Womens Health. 2009;18(3):311-319.

ECRI Institute. Hormonal treatment with GnRH analogues to suppress puberty in transgender children and adolescents. Plymouth Meeting (PA): ECRI Institute; 2016 Jun 20. (Custom Rapid Responses).

Eligard (Leuprolide acetate for injectable suspension). Tolmar Pharmaceuticals, Inc. 07/2023. Available at: http://eligard.com/. Accessed August 10, 2023.

Elsevier's Clinical Pharmacology Compendium. Leuprolide. [ClinicalKey Web site]. 07/27/2023. Available at: https://www.clinicalkey.com/pharmacology/. [via subscription only]. Accessed August 15, 2023.

Fensolvi. (Leuprolide acetate for injectable suspension). Tolmar Pharmaceuticals, Inc; Fort Collins, CO. 11/2022. Available at: https://fensolvi.com/. Accessed August 10, 2023.

Guss C, Shumer D, Katz-Wise S. Transgender and gender nonconforming adolescent care: Psychosocial and medical considerations. Curr Opin Pediatr. 2015;26(4):421-426.

Hembree W, Cohen-Kettenis P, Delemarre-van de Waal H, et al. Endocrine treatment of transsexual persons: An Endocrine Society clinical practice guidelines. J Clin Endocrinol Metab.2009;94(9):3132-3154.

Lexi-Drugs Compendium. Leuprolide. [Lexicomp Online Web site]. 08/23/2023. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed August 23, 2023.

Lexi-Drugs Compendium: Pediatric and Neonatal. Leuprolide. [Lexicomp Online Web site]. 08/23/2023. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed August 23, 2023.

Lupron Depot® (Leuprolide acetate for depot suspension). AbbVie Inc. Prostate Cancer Indications: Updated 04/2022. Endometriosis and Fibroid Indications: 11.25 mg updated 03/2020; 3.75 mg updated 01/2023. Available at: http://www.lupron.com/. Accessed August 23, 2023.

Lupron Depot-PED® (Leuprolide acetate for depot suspension). AbbVie Inc. 04/2023. Available at: http://www.lupron.com/. Accessed August 23, 2023.

Micromedex® Healthcare Series. Leuprolide Acetate. [Micromedex Web site]. Last modified 08/12/2023. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed August 14, 2023.

National Comprehensive Cancer Network (NCCN). NCCN Drugs & Biologics Compendium. Leuprolide acetate, Leuprolide acetate for depot suspension, Leuprolide mesylate. [NCCN Web site]. 2023. Available at: https://www.nccn.org/professionals/drug_compendium/content/ [via subscription only]. Accessed August 17, 2023.

National Comprehensive Cancer Network (NCCN). NCCN Guidelines Clinical Practice Guidelines in Oncology: Breast Cancer V4.2023. [NCCN Web site]. 03/23/2023. Available at: https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf [via subscription only]. Accessed August 17, 2023.

National Comprehensive Cancer Network (NCCN). NCCN Guidelines Clinical Practice Guidelines in Oncology: Head and Neck Cancers V2.2023. [NCCN Web site]. 05/15/2023. Available at: https://www.nccn.org/professionals/physician_gls/pdf/head-and-neck.pdf [via subscription only]. Accessed August 17, 2023.

National Comprehensive Cancer Network (NCCN). NCCN Guidelines Clinical Practice Guidelines in Oncology: Ovarian Cancer V2.2023. [NCCN Web site]. 06/02/2023. Available at: https://www.nccn.org/professionals/physician_gls/pdf/ovarian.pdf [via subscription only]. Accessed August 17, 2023.

National Comprehensive Cancer Network (NCCN). NCCN Guidelines Clinical Practice Guidelines in Oncology: Prostate Cancer V3.2023. [NCCN Web site]. 08/07/2023. Available at: https://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf [via subscription only]. Accessed August 17, 2023.

Rugo H, Rumble B, Macrae E, et al. Endocrine therapy for hormone receptor-positive metastatic breast cancer: American Society of Clinical Oncology guideline. J Clin Oncol. 2016;34(25):3069-3103.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Leuprolide acetate for depot suspension (LUPRON DEPOT 3.75 mg) prescribing information. [FDA Web site]. 01/2023. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed August 10, 2023.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Leuprolide acetate for depot suspension (LUPRON DEPOT 7.5, 22.5, 30, 45 mg) prescribing information. [FDA Web site]. 04/2022. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed August 10, 2023.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Leuprolide acetate for depot suspension (LUPRON DEPOT 11.25 mg) prescribing information. [FDA Web site]. 03/2020. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed August 10, 2023.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Leuprolide acetate for depot suspension (LUPRON DEPOT-PED) prescribing information. [FDA Web site]. 04/2023. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed August 10, 2023.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Leuprolide acetate for injectable suspension, subcutaneous (Fensolvi) prescribing information. [FDA Web site]. 11/2022. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed August 10, 2023.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Leuprolide acetate (ELIGARD) prescribing information. [FDA Web site]. Revised 07/2023. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed August 10, 2023.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Leuprolide injectable emulsion, for subcutaneous use (Camcevi) prescribing information. [FDA Web site]. 05/25/2021. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed August 10, 2023.

World Professional Association for Transgender Health (WPATH). Standards of Care for the Health of Transgender and Gender Diverse People, Version 8. 09/15/2022. Available at: https://www.wpath.org/publications/soc. Accessed August 30, 2023.

Coding

CPT Procedure Code Number(s)

N/A

ICD - 10 Procedure Code Number(s)

N/A

ICD - 10 Diagnosis Code Number(s)

See Attachment A, B, C, and D.

HCPCS Level II Code Number(s)

THE FOLLOWING HCPCS CODE IS USED TO REPRESENT LUPRON DEPOT

J1950 Injection, leuprolide acetate (for depot suspension), per 3.75mg

THE FOLLOWING HCPCS CODE IS USED TO REPRESENT FENSOLVI

J1951 Injection, leuprolide acetate for depot suspension (fensolvi), 0.25 mg

THE FOLLOWING HCPCS CODE IS USED TO REPRESENT CAMCEVI

J1952 Leuprolide injectable, camcevi, 1 mg

THE FOLLOWING HCPCS CODE IS USED TO REPRESENT ELIGARD AND LUPRON DEPOT

J9217 Leuprolide acetate (for depot suspension), 7.5 mg

Revenue Code Number(s)

N/A

MPMiscCodesNarrativesPub

Coding and Billing Requirements

Cross Reference

Policy History

Revisions From 08.01.33i:

10/23/2023

This version of the policy will become effective 10/23/2023.

This policy was updated to communicate the Company's coverage position for gonadotropin-releasing hormone agonist (Camcevi, Eligard, Fensolvi, Lupron Depot), in accordance with US Food and Drug Administration (FDA), National Comprehensive Cancer Network (NCCN), and other Company-recognized Drug Compendia.

Policy criteria revisions were made to ovarian cancer and prostate cancer per National Comprehensive Cancer Network (NCCN).

Revisions From 08.01.33h:

01/02/2023

This version of the policy will become effective 01/02/2023.

This policy was updated to communicate the Company's coverage position for Gonadotropin-Releasing Hormone Agonist (Camcevi, Eligard, Fensolvi, Lupron Depot), in accordance with US Food and Drug Administration (FDA), National Comprehensive Cancer Network (NCCN), and other Company-recognized Drug Compendia.

Policy criteria revisions were made to inflammatory breast cancer, ovarian cancer, and prostate cancer, per US Food and Drug Administration (FDA) labeling or National Comprehensive Cancer Network (NCCN).

The coverage positions were added/revised for the following HCPCS codes:

J1950 Lupron Depot: Coverage changed from NOT Medically Necessary to Medically Necessary for Breast cancer and Ovarian Cancer/Fallopian Tube Cancer/Primary Peritoneal Cancers. Added NOT Medically Necessary coverage for prostate cancer.
J1951 Fensolvi: Coverage changed from Medically Necessary to NOT Medically Necessary for Endometriosis, uterine fibroids, gender dysphoria, since not clinically appropriate per Drug Compendia. Added NOT Medically Necessary coverage for prostate cancer.
J1952 Camcevi: Added NOT Medically Necessary coverage for all indications listed in the policy, due to the Company's Benefit language definition for Medical Necessity.

The following HCPCS code has been added to this policy:

J1952 Leuprolide injectable, camcevi, 1 mg

The following ICD-10 CM codes have been added to this policy as Medically Necessary for LEUPROLIDE ACETATE 3.75 mg (J1950):

C48.1, C48.2, C48.8, C50.011, C50.012, C50.019, C50.021, C50.022, C50.029, C50.111,

C50.112, C50.119, C50.121, C50.122, C50.129, C50.211, C50.212, C50.219, C50.221,

C50.222, C50.229, C50.311, C50.312, C50.319, C50.321, C50.322, C50.329, C50.411 ,

C50.412, C50.419, C50.421, C50.422, C50.429, C50.511, C50.512, C50.519,

C50.521, C50.522, C50.529, C50.611, C50.612, C50.619, C50.621, C50.622, C50.629,

C50.811, C50.812, C50.819, C50.821, C50.822, C50.829, C50.911, C50.912, C50.919,

C50.921, C50.922, C50.929, C56.1, C56.2, C56.3, C56.9, C57.00, C57.01, C57.02,

C57.10, C57.11, C57.12, C57.20, C57.21, C57.22, C57.3, C57.4, C79.81, C79.82

The following ICD-10 codes have been added to this policy as Not Medically Necessary for LEUPROLIDE ACETATE 3.75 mg (J1950):

C07 Malignant neoplasm of parotid gland
C08.0 Malignant neoplasm of submandibular gland
C08.1 Malignant neoplasm of sublingual gland
C08.9 Malignant neoplasm of major salivary gland, unspecified
C61 Malignant neoplasm of prostate

The following ICD-10 CM code coverage has revised in this policy From Medically Necessary TO NOT Medically Necessary for LEUPROLIDE ACETATE 0.25 mg (J1951) Fensolvi:

D25.0, D25.1, D25.2, D25.9, E22.8, F64.0, F64.1, F64.2, F64.8, F64.9, N80.0, N80.6, N80.8, N80.9, N80.101, N80.102, N80.103, N80.111, N80.112, N80.113, N80.121, N80.122, N80.123, N80.201, N80.202, N80.203, N80.211, N80.212, N80.213, N80.221, N80.222, N80.223, N80.30 , N80.311, N80.312, N80.319, N80.321, N80.322, N80.329, N80.331, N80.332, N80.333, N80.341, N80.342, N80.343, N80.351, N80.352, N80.353, N80.361, N80.362, N80.363, N80.371, N80.372, N80.373, N80.381, N80.382, N80.383, N80.391, N80.392, N80.399, N80.3A1, N80.3A2, N80.3A3, N80.3B1, N80.3B2, N80.3B3, N80.3C1, N80.3C2, N80.3C3, N80.40 , N80.41 , N80.42 , N80.50 , N80.511, N80.512, N80.519, N80.521, N80.522, N80.529, N80.531, N80.532, N80.539, N80.541, N80.542, N80.549, N80.551, N80.552, N80.559, N80.561, N80.562, N80.569, N80.A0 , N80.A1 , N80.A2 , N80.A41, N80.A42, N80.A43, N80.A49, N80.A51, N80.A52, N80.A53, N80.A59, N80.A61, N80.A62, N80.A63, N80.A69, N80.B1 , N80.B2 , N80.B31, N80.B32, N80.B39, N80.B4 , N80.B5 , N80.B6 , N80.C0 , N80.C10, N80.C11, N80.C19, N80.C2 , N80.C3, N80.C4 , N80.C9, N80.D0, N80.D1, N80.D2, N80.D3, N80.D4, N80.D5, N80.D6, N80.D9.

The following ICD-10 codes have been added to this policy as Not Medically Necessary for LEUPROLIDE ACETATE 0.25 mg (J1951) Fensolvi:
C07, C08.0, C08.1, C08.9, C48.1, C48.2, C48.8, C50.011, C50.012, C50.019, C50.021, C50.022, C50.029, C50.111, C50.112, C50.119, C50.121, C50.122, C50.129, C50.211, C50.212, C50.219, C50.221, C50.222, C50.229, C50.311, C50.312, C50.319, C50.321, C50.322, C50.329, C50.411, C50.412, C50.419, C50.421, C50.422, C50.429, C50.511, C50.512, C50.519, C50.521, C50.522, C50.529, C50.611, C50.612, C50.619, C50.621, C50.622, C50.629, C50.811, C50.812, C50.819, C50.821, C50.822, C50.829, C50.911, C50.912, C50.919, C50.921, C50.922, C50.929, C56.1, C56.2, C56.3, C56.9, C57.00, C57.01, C57.02, C57.10, C57.11, C57.12, C57.20, C57.21, C57.22, C57.3, C57.4, C61, C79.81, C79.82.

The following ICD-10 codes have been added to this policy as Not Medically Necessary for J1952 Camcevi:

C07, C08.0, C08.1, C08.9, C48.1, C48.2, C48.8, C50.011, C50.012, C50.019, C50.021, C50.022, C50.029, C50.111, C50.112, C50.119, C50.121, C50.122, C50.129, C50.211, C50.212, C50.219, C50.221, C50.222, C50.229, C50.311, C50.312, C50.319, C50.321, C50.322, C50.329, C50.411, C50.412, C50.419, C50.421, C50.422, C50.429, C50.511, C50.512, C50.519, C50.521, C50.522, C50.529, C50.611, C50.612, C50.619, C50.621, C50.622, C50.629, C50.811, C50.812, C50.819, C50.821, C50.822, C50.829, C50.911, C50.912, C50.919, C50.921, C50.922, C50.929, C56.1, C56.2, C56.3, C56.9, C57.00, C57.01, C57.02, C57.10, C57.11, C57.12, C57.20, C57.21, C57.22, C57.3, C57.4, C61, C79.81, C79.82, D25.0, D25.1, D25.2, D25.9, E22.8, E30.1, F64.0, F64.1, F64.2, F64.8, F64.9, N80.0, N80.6, N80.8, N80.9, N80.101, N80.102, N80.103, N80.111, N80.112, N80.113, N80.121, N80.122, N80.123, N80.201, N80.202, N80.203, N80.211, N80.212, N80.213, N80.221, N80.222, N80.223, N80.30 , N80.311, N80.312, N80.319, N80.321, N80.322, N80.329, N80.331, N80.332, N80.333, N80.341, N80.342, N80.343, N80.351, N80.352, N80.353, N80.361, N80.362, N80.363, N80.371, N80.372, N80.373, N80.381, N80.382, N80.383, N80.391, N80.392, N80.399, N80.3A1, N80.3A2, N80.3A3, N80.3B1, N80.3B2, N80.3B3, N80.3C1, N80.3C2, N80.3C3, N80.40 , N80.41 , N80.42 , N80.50 , N80.511, N80.512, N80.519, N80.521, N80.522, N80.529, N80.531, N80.532, N80.539, N80.541, N80.542, N80.549, N80.551, N80.552, N80.559, N80.561, N80.562, N80.569, N80.A0 , N80.A1 , N80.A2 , N80.A41, N80.A42, N80.A43, N80.A49, N80.A51, N80.A52, N80.A53, N80.A59, N80.A61, N80.A62, N80.A63, N80.A69, N80.B1 , N80.B2 , N80.B31, N80.B32, N80.B39, N80.B4 , N80.B5 , N80.B6 , N80.C0 , N80.C10, N80.C11, N80.C19, N80.C2 , N80.C3 , N80.C4 , N80.C9 , N80.D0 , N80.D1 , N80.D2 , N80.D3 , N80.D4 , N80.D5 , N80.D6 , N80.D9.

Revisions From 08.01.33g:

10/01/2022

This version of the policy will become effective 10/01/2022.

The following ICD-10 CM codes have been termed (no longer valid codes) and removed from this policy:

N80.1 Endometriosis of ovary, N80.2 Endometriosis of fallopian tube, N80.3 Endometriosis of pelvic peritoneum, N80.4 Endometriosis of rectovaginal septum and vagina, N80.5 Endometriosis of intestine

The following ICD-10 CM codes have been added to this policy: N80.101, N80.102, N80.103, N80.111, N80.112, N80.113, N80.121, N80.122, N80.123, N80.201, N80.202, N80.203, N80.211, N80.212, N80.213, N80.221, N80.222, N80.223, N80.30, N80.311, N80.312, N80.319, N80.321, N80.322, N80.329, N80.331, N80.332, N80.333, N80.341, N80.342, N80.343, N80.351, N80.352, N80.353, N80.361, N80.362, N80.363, N80.371, N80.372, N80.373, N80.381, N80.382, N80.383, N80.391, N80.392, N80.399, N80.3A1, N80.3A2, N80.3A3, N80.3B1, N80.3B2, N80.3B3, N80.3C1, N80.3C2, N80.3C3, N80.40, N80.41, N80.42, N80.50, N80.511, N80.512, N80.519, N80.521, N80.522, N80.529, N80.531, N80.532, N80.539, N80.541, N80.542, N80.549, N80.551, N80.552, N80.559, N80.561, N80.562, N80.569, N80.A0, N80.A1, N80.A2, N80.A41, N80.A42, N80.A43, N80.A49, N80.A51, N80.A52, N80.A53, N80.A59, N80.A61, N80.A62, N80.A63, N80.A69, N80.B1, N80.B2, N80.B31, N80.B32, N80.B39, N80.B4, N80.B5, N80.B6, N80.C0, N80.C10, N80.C11, N80.C19, N80.C2, N80.C3, N80.C4, N80.C9, N80.D0, N80.D1, N80.D2, N80.D3, N80.D4, N80.D5, N80.D6, N80.D9.

Revisions From 08.01.33f:

10/25/2021

This version of the policy will become effective 10/25/2021.

This policy was updated to communicate the Company's coverage position for Gonadotropin-Releasing Hormone Agonist (Eligard®, Fensolvi®, Lupron Depot®), in accordance with US Food and Drug Administration (FDA) and National Comprehensive Cancer Network (NCCN).

The following criteria have been added to this policy:

Inflammatory breast cancer

The following policy criteria have been revised:

Revisions made to Ovarian cancer, per NCCN.

Extensive revisions made to Prostate cancer, per NCCN.

Revisions From 08.01.33e:

10/01/2021

This policy has been identified for the ICD-10 CM code update, effective 10/01/2021.

The following ICD-10 CM code has been added to this policy for HCPCS J9217:

C56.3 Malignant neoplasm of bilateral ovaries

Revisions From 08.01.33d:

07/01/2021

This policy has been updated to communicate the HCPCS code change for leuprolide acetate (Fensolvi).

The following HCPCS code has been removed from this policy for leuprolide acetate (Fensolvi) and is replaced by the following HCPCS code:

FROM: J1950 Injection, leuprolide acetate (for depot suspension), per 3.75 mg
TO: J1951 Injection, leuprolide acetate for depot suspension (fensolvi), 0.25 mg

Note: J1950 will continue to represent Lupron Depot 3.75 mg

Revisions From 08.01.33c:

03/08/2021

This policy has been updated to communicate the coverage position of leuprolide acetate (Fensolvi), represented by HCPCS J1950. Additionally, the medical necessity criteria have been revised to reflect the updated coverage position from the National Comprehensive Cancer Network (NCCN) for endometriosis, head and neck cancers, ovarian cancer, and prostate cancer.

Revisions From 08.01.33b:

12/02/2019

This policy has undergone a routine review and the medical necessity criteria have been revised to reflect the updated coverage position from the National Comprehensive Cancer Network (NCCN) for head and neck cancers, breast cancer, ovarian cancer, and prostate cancer. Criteria changes have been made for the coverage of gender dysphoria.

Revisions From 08.01.33a:

02/19/2018

This policy has undergone a routine review, and the medical necessity criteria have been revised for the indication of Prostate Cancer.

Effective 10/05/2017 this policy has been updated to the new policy template format.

Version Effective Date:

10/23/2023

Version Issued Date:

10/23/2023

Version Reissued Date: