Bremelanotide (Vyleesi) Form

Bremelanotide (Vyleesi™) is a melanocortin receptor agonist. FDA Approved Indication(s) Vyleesi is indicated for the treatment of premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD) as characterized by low sexual desire that causes marked distress or interpersonal difficulty and NOT due to: • A co-existing medical or psychiatric condition, • Problems with the relationship, or • The effects of a medication or drug substance. Limitation(s) of use: • Not indicated for treatment of HSDD in postmenopausal women or in men. • Not indicated to enhance sexual performance. 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 Vyleesi is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Hypoactive Sexual Desire Disorder (must meet all):

1. Diagnosis of HSDD in premenopausal women;
2. Age ≥ 18 years;
3. Failure of a 3-month trial of bupropion at up to maximally studied effective doses (see Appendix B), unless contraindicated or clinically significant adverse effects are experienced;
   4. HSDD symptoms have persisted for a minimum of 6 months;
4. HSDD is not attributed to any of the following (a, b, or c): a. A co-existing medical or psychiatric condition;
   b. Problems within the relationship;
   c. Effects of a medication or other drug substance;
5. Vyleesi is not prescribed concurrently with Addyi®;

6. Dose does not exceed both of the following (a and b):
   a. 1.75 mg (1 injection) per day; Page 1 of 7

   CLINICAL POLICY Bremelanotide b. 8 doses per month. Approval duration: 3 months B. 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 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 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 and CP.PMN.53 for Medicaid.
      II. Continued Therapy A. Hypoactive Sexual Desire Disorder (must meet all):
7. 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);
8. Member is responding positively to therapy;

9. If request is for a dose increase, new dose does not exceed both of the following (a and b):
   a. 1.75 mg (1 injection) per day;
   b. 8 doses per month. Approval duration:
   Medicaid – 12 months Commercial – 6 months or duration of request, whichever is less B. 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 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 and CP.PMN.16 for Medicaid; or Page 2 of 7

   CLINICAL POLICY Bremelanotide

   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 and CP.PMN.53 for Medicaid.
      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 and CP.PMN.53 for Medicaid or evidence of coverage documents.
      IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key DSM: Diagnostic and Statistical Manual of Mental Disorders
      FDA: Food and Drug Administration HSDD: hypoactive sexual desire disorder Appendix B: Therapeutic Alternatives
      This table provides a listing of preferred alternative therapy recommended in the approval criteria. The drugs listed here may not be a formulary agent for all relevant lines of business and may require prior authorization.
      Drug Name Dose Limit/Maximum Dose Dosing Regimen Varies bupropion (Aplenzin®, Forfivo XL®, Wellbutrin®, Wellbutrin SR®, Wellbutrin XL®) Therapeutic alternatives are listed as Brand name® (generic) when the drug is available by brand name only and generic (Brand name®) when the drug is available by both brand and generic. Immediate-release: 450 mg/day (300 mg/day if pediatric)
      Sustained-release: 400 mg/day
      Extended-release (HCl): 450 mg/day
      Extended-release (HBr): 522 mg/day Appendix C: Contraindications/Boxed Warnings • Contraindication(s): uncontrolled hypertension or known cardiovascular disease • Boxed warning(s): none reported Appendix D: General Information • HSDD is characterized by a deficiency or absence of sexual fantasies and desire for sexual activity which causes marked distress or interpersonal difficulty, and is not better accounted for by another psychiatric disorder or due exclusively to the direct physiological effects of a substance or to the direct physiological effects of another medical condition. HSDD does not encompass normal (e.g., daily or weekly) fluctuations in levels of desire. • There is currently no published data demonstrating the efficacy of Vyleesi in the treatment of HSDD in postmenopausal women or in men. • Treatment should be discontinued after 8 weeks if there is no improvement in symptoms. Page 3 of 7

   CLINICAL POLICY Bremelanotide • In the DSM-5, female hypoactive sexual desire disorder was merged with female arousal dysfunction and is now reclassified as one disorder: female sexual interest/arousal disorder. • All of the DSM-5 sexual dysfunctions (except substance-/medication-induced sexual dysfunction) now require a minimum duration of approximately 6 months and more precise severity criteria to improve precision regarding duration and severity criteria and to reduce the likelihood of over-diagnosis. These changes provide useful thresholds for making a diagnosis and distinguish transient sexual difficulties from more persistent sexual dysfunction. • Two randomized trials (Segraves RT, et al. and Safarinejad MR, et al.) of premenopausal women with HSDD and without underlying depression reported increased sexual pleasure, desire, arousal, and orgasm with bupropion compared with placebo. • Examples of co-existing psychiatric conditions include a history of major depressive disorder within the previous six months, a current diagnosis of mild to severe depression using a validated depression scale. • Examples of co-existing medical condition that could contribute to sexual dysfunction include pelvic inflammatory disease, cervicitis, interstitial cystitis, vulvodynia, significant vaginal atrophy, sexual pain. • Examples of medications associated with low sexual desire among women:
   o Cardiac and antihypertensive: lipid-lowering medications, beta-blockers, clonidine, digitalis, methyldopa, spironolactone
   o Hormonal: androgen antagonists, gonadotropin-releasing hormone agonists and analogs, oral contraceptives, tamoxifen o Opioids: any opioids used chronically, methadone
   o Psychotropic: antipsychotics, barbiturates, benzodiazepines, lithium, monoamine oxidase inhibitors, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants
   o Other: aromatase inhibitors, chemotherapy, histamine 2 receptor blockers, nonsteroidal anti-inflammatory agents, ketoconazole
   V. Dosage and Administration
   Indication HSDD Dosing Regimen 1.75 mg SC in abdomen or thigh, as needed, at least 45 minutes before anticipated sexual activity Maximum Dose 1.75 mg/day (max 8 doses/month) VI. Product Availability
   Single-dose prefilled autoinjector: 1.75 mg/0.3 mL VII.