TRIPTODUR, Triptorelin Pamoate (CPP) TRELSTAR, Triptorelin Pamoate Form

Triptorelin pamoate (Trelstar®, Triptodur®) is a gonadotropin-releasing hormone (GnRH) receptor agonist. FDA Approved Indication(s) Trelstar is indicated for the palliative treatment of advanced prostate cancer. Triptodur is indicated for the treatment of pediatric patients 2 years and older with central precocious puberty (CPP). Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria.
It is the policy of health plans affiliated with Centene Corporation® that Trelstar and Triptodur are medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Prostate Cancer (must meet all):

1. Diagnosis of prostate cancer;
2. Request is for Trelstar;
3. Prescribed by or in consultation with an oncologist or urologist;
4. Age ≥ 18 years;

5. Request meets one of the following (a or b): a. Dose does not exceed 3.75 mg per 4 weeks, 11.25 mg per 12 weeks, or 22.5 mg per 24 weeks; b. Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). Prescribed regimen must be FDA-approved or recommended by NCCN Approval duration:
   HIM/Medicaid – 12 months Commercial – 6 months or to member’s renewal date, whichever is longer B. Central Precocious Puberty (must meet all):

   1. Diagnosis of CPP confirmed by all of the following (a, b, and c): Page 1 of 9

   CLINICAL POLICY Triptorelin Pamoate a. Elevated basal luteinizing hormone (LH) level > 0.2 - 0.3 mIU/mL (dependent on type of assay used) and/or elevated leuprolide-stimulated LH level > 3.3 - 5 IU/L (dependent on type of assay used); b. Difference between bone age and chronological age was > 1 year (bone age- chronological age); c. Age at onset of secondary sex characteristics (1 or 2): 1) Female: < 8 years; 2) Male: < 9 years;

6. Request is for Triptodur;
7. Prescribed by or in consultation with a pediatric endocrinologist;
8. Member meets one of the following age requirements (a or b):
   a. Female: 2 - 11 years; b. Male: 2 - 12 years;
   5. Dose does not exceed 22.5 mg per 24 weeks. Approval duration:
      HIM/Medicaid – 12 months Commercial – 6 months or to member’s renewal date, whichever is longer C. Gender Dysphoria, Gender Transition (off-label) (must meet all):
9. Diagnosis of gender dysphoria or request is for gender transition;
10. Prescribed by or in consultation with both of the following (a and b): a. An endocrinologist; b. A provider with expertise in gender dysphoria and transgender medicine based on a certified training program or affiliation with local transgender health services (e.g., mental health professional such as psychologist, psychiatrist, see Appendix D);
    3. Age and pubertal development – meets one of the following (a or b): a. Member is < 18 years of age and has reached or passed through Tanner Stage 2;
       Age ranges approximating Tanner Stage 2 pubertal development extend from 8 to 13 years of age in girls and 9 to 14 years of age in boys. b. Member is ≥ 18 years of age and has failed to achieve physiologic hormone levels with gender-affirming hormonal therapy (e.g., estrogen, testosterone) unless contraindicated or clinically significant adverse effects are experienced;
11. Member demonstrates understanding of expected GnRH analogue treatment outcomes and has given consent for such treatment;
    5. If member has a psychiatric comorbidity, member is followed by mental health provider;
    6. Psychosocial support will be provided during treatment;

12. Dose is within FDA maximum limit for any FDA-approved indication (see Section V) or is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence).
    Approval duration:
    HIM/Medicaid – 12 months Commercial – 6 months or to member’s renewal date, whichever is longer Page 2 of 9

    CLINICAL POLICY Triptorelin Pamoate D. Other diagnoses/indications (must meet 1 or 2):

    1. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or
    2. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
       II. Continued Therapy A. Prostate Cancer (must meet all):
    3. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Trelstar for prostate cancer and has received this medication for at least 30 days;
    4. Request is for Trelstar;
13. Member is responding positively to therapy;
14. If request is for a dose increase, request meets one of the following (a or b): a. New dose does not exceed 3.75 mg per 4 weeks, 11.25 mg per 12 weeks, or 22.5 mg per 24 weeks; b. New dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). Prescribed regimen must be FDA-approved or recommended by NCCN Approval duration: HIM/Medicaid – 12 months Commercial – 6 months or to member’s renewal date, whichever is longer B. Central Precocious Puberty (must meet all):
    1. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; b. Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B);
    2. Request is for Triptodur;

15. Member is responding positively to therapy as evidenced by, including but not limited to, improvement in any of the following parameters: decreased growth Page 3 of 9

    CLINICAL POLICY Triptorelin Pamoate velocity, cessation of menses, softening of breast tissue or testes, arrested pubertal progression;

    4. Member meets one of the following age requirement (a or b):
       a. Female: ≤ 11 years; b. Male: ≤ 12 years.
    5. If request is for a dose increase, new dose does not exceed: 22.5 mg per 24 weeks. Approval duration: HIM/Medicaid – 12 months Commercial – 6 months or to member’s renewal date, whichever is longer C. Gender Dysphoria, Gender Transition (off-label) (must meet all):
    6. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; b. Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B);
    7. Member is responding positively to therapy (e.g., member continues to meet their individual goals of therapy for gender dysphoria);
    8. If request is for a dose increase, new dose is within FDA maximum limit for any FDA-approved indication (see Section V) or is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence).
       Approval duration:
       HIM/Medicaid – 12 months Commercial – 6 months or to member’s renewal date, whichever is longer D. Other diagnoses/indications (must meet 1 or 2):
    9. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or
    10. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
        Page 4 of 9

    CLINICAL POLICY Triptorelin Pamoate III. Diagnoses/Indications for which coverage is NOT authorized:
    A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policies – CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid, or evidence of coverage documents.
    IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key CPP: central precocious puberty DSM-5: Diagnostic and Statistical Manual of Mental Disorders, 5th edition FDA: Food and Drug Administration GnRH: gonadotropin-releasing hormone
    Appendix B: Therapeutic Alternatives
    Not applicable LH: luteinizing hormone NCCN: National Comprehensive Cancer Network WPATH: World Professional Association for Transgender Health Appendix C: Contraindications/Boxed Warnings • Contraindication(s): o Hypersensitivity to triptorelin or any other component of the product, or other GnRH agonists or GnRH o Pregnancy (Triptodur) • Boxed warning(s): none reported Appendix D: General Information • World Professional Association for Transgender Health (WPATH) offers their Global Education Institute (GEI) Certified Training Courses: Best Practices in Transgender Medical and Mental Health Care. Additionally, the following link provides a search tool to locate WPATH member providers: https://www.wpath.org/provider/search • Transgender Care Therapy Certification Training is also offered by the International Transgender Certification Association (ITCA). Professionals with expertise in transgender care can be located using the following search tool: https://transgendercertification.com/locate-a-professional/ • The WPATH Standards of Care Version 8 recommend that adolescents are managed by a multidisciplinary care team that involves both medical and mental health professionals. The list of key disciplines includes but is not limited to: adolescent medicine/primary care, endocrinology, psychology, psychiatry, speech/language pathology, fertility, social work, support staff, and the surgical team. The need to include a healthcare professional with some expertise in mental health does not dictate the inclusion of a psychologist, psychiatrist or social work in every assessment. Instead, a general practitioner, nurse or other qualified clinician could fulfill this requirement as long as they have sufficient expertise to diagnose gender incongruence, recognize mental health concerns, distinguish between these concerns and gender dysphoria, incongruence or diversity, assist a transgender person in care planning and preparing for gender affirmative medical and surgical treatments, and refer to a mental health professional if needed. Page 5 of 9

    CLINICAL POLICY Triptorelin Pamoate V. Dosage and Administration
    Drug Name Indication Dosing Regimen Triptorelin pamoate (Trelstar) Triptorelin pamoate Triptodur) May be used in combination with therapies such as radiation therapy, antiandrogens, glucocorticoids, docetaxel. IM: 3.75 mg per 4 weeks; 11.25 mg per 12 weeks; 22.5 mg per 24 weeks IM: 22.5 mg IM every 24 weeks Prostate cancer CPP Maximum Dose See regimen See regimen VI. Product Availability
    Drug Name Triptorelin pamoate (Trelstar) Triptorelin pamoate (Triptodur) Availability Single-dose vial for reconstitution with Mixject system (kit): 3.75 mg, 11.25 mg, 22.5 mg Single-dose vial for reconstitution (kit): 22.5 mg VII.