Telotristat Ethyl (Xermelo) Form

Telotristat ethyl (Xermelo®) is a tryptophan hydroxylase inhibitor. FDA Approved Indication(s) Xermelo is indicated for the treatment of carcinoid syndrome diarrhea in combination with somatostatin analog (SSA) therapy in adults inadequately controlled by SSA therapy. 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 Xermelo is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Carcinoid Syndrome Diarrhea (must meet all):

1. Diagnosis of carcinoid syndrome diarrhea;

2. Failure of a one month trial of an SSA (e.g., octreotide, lanreotide) at up to maximally indicated doses, unless clinically significant adverse effects are experienced or all are contraindicated;

   3. Xermelo is prescribed in combination with an SSA, unless clinically significant adverse effects are experienced or all are contraindicated;
   4. For Xermelo requests, member must use telotristat ethyl, if available, unless contraindicated or clinically significant adverse effects are experienced;
   5. Dose does not exceed both of the following (a and b):
      a. 750 mg per day; b. 3 tablets per day. Approval duration: 6 months B. Other diagnoses/indications (must meet 1 or 2):
   6. 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 Page 1 of 6

   CLINICAL POLICY
   Telotristat Ethyl 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. Carcinoid Syndrome Diarrhea (must meet all):
3. 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. Member is responding positively to therapy (see Appendix D for examples);
4. Member continues to have diarrhea;

5. Xermelo is prescribed in combination with an SSA, unless clinically significant adverse effects are experienced or all are contraindicated;

   5. For Xermelo requests, member must use telotristat ethyl, if available, unless contraindicated or clinically significant adverse effects are experienced;
   6. If request is for a dose increase, new dose does not exceed both of the following (a and b):
      a. 750 mg per day;
      b. 3 tablets per day. Approval duration: 12 months B. Other diagnoses/indications (1 or 2):
   7. 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
   8. 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 Page 2 of 6

   CLINICAL POLICY
   Telotristat Ethyl of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, 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, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid, or evidence of coverage documents; B. Other symptoms of carcinoid syndrome (e.g., flushing, abdominal pain, venous telangiectasia, bronchospasm, cardiac valvular lesions). IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key 5-HIAA: 5-hydroxyindoleacetic acid FDA: Food and Drug Administration SSA: somatostatin analog 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 Dosing Regimen Sandostatin®, Sandostatin® LAR Depot (octreotide) Somatuline® Depot (lanreotide) Severe diarrhea or flushing associated with carcinoid syndrome: Sandostatin 100-600 mcg/day SC in 2-4 divided doses for 2 weeks, followed by Sandostatin LAR 20 mg IM every 4 weeks for 2 months; at 2 months, can reduce (10 mg) or increase (30 mg) dose as needed Gastroenteropancreatic neuroendrocrine tumors: 120 mg SC every 4 weeks Dose Limit/
   Maximum Dose Sandostatin: 600 mcg/day Sandostatin LAR: 30 mg/4 weeks 120 mg/4 weeks 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. Appendix C: Contraindications/Boxed Warnings • Contraindication(s): history of hypersensitivity to telotristat • Boxed warning(s): none reported
   Appendix D: Management of Carcinoid Syndrome • SSA therapy is the standard of care for carcinoid syndrome. While SSAs are highly effective, tachyphylaxis is a well-known occurrence. The duration of response to SSA therapy varies; some patients lose effectiveness within months of treatment initiation Page 3 of 6

   CLINICAL POLICY
   Telotristat Ethyl • • while others are able to retain control for years. Examples of inadequate response to SSA therapy include reduction of bowel movement by less than 3 or by less than 25%, or 4 or more bowel movements per day. Interferon alfa has historically been used to manage carcinoid syndrome as a second-line therapy in patients who are refractory to SSA therapy. It relieves symptoms such as diarrhea and flushing in 40-50% of patients, but its use is largely limited by side effects such as fatigue, depression, myelosuppression, flu-like symptoms, weight loss, and alteration of thyroid function. In Xermelo’s phase 3 trial TELESTAR, a reduction in bowel movement frequency was observed as early as 1-3 weeks of starting therapy and persisted for the remaining 9 weeks of the study. A 36-week open-label extension is currently ongoing to assess if response is sustained. • Examples of positive response to therapy may include, but are not limited to: o Reduction in bowel movement frequency o Reduction in urinary 5-HIAA levels V. Dosage and Administration
   Indication Carcinoid syndrome diarrhea VI. Product Availability
   Tablet: 250 mg Dosing Regimen 250 mg PO TID Maximum Dose 750 mg/day VII.