Clinical Policy: Telotristat Ethyl (Xermelo) Form

Page 1 of 6 Clinical Policy: Telotristat Ethyl (Xermelo) Reference Number: CP.PHAR.337 Effective Date: 06.01.17 Last Review Date: 05.26 Line of Business: Commercial, HIM/ICHRA, Medicaid

Revision Log

See Important Reminder at the end of this policy for important regulatory and legal information.

Description
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.

CLINICAL POLICY

Telotristat Ethyl

Page 2 of 6 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/ICHRA) 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/ICHRA, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace/ICHRA) 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/ICHRA, 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/ICHRA, 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);
4. Member is responding positively to therapy (e.g., reduction in bowel movement frequency, reduction in urinary 5-HIAA levels);
5. Member continues to have diarrhea;
6. Xermelo is prescribed in combination with an SSA, unless clinically significant adverse effects are experienced or all are contraindicated;
7. For Xermelo requests, member must use telotristat ethyl, if available, unless contraindicated or clinically significant adverse effects are experienced;

8. 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):

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/ICHRA) or PDL (Medicaid), the no coverage criteria policy for the relevant line of

CLINICAL POLICY

Telotristat Ethyl

Page 3 of 6 business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace/ICHRA, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace/ICHRA) 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/ICHRA, 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/ICHRA, 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/ICHRA, 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 Dose Limit/
   Maximum Dose octreotide (Sandostatin®, Sandostatin® LAR Depot) 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 Sandostatin: 600 mcg/day

   Sandostatin LAR: 30 mg/4 weeks lanreotide (Somatuline® Depot) Gastroenteropancreatic neuroendrocrine tumors: 120 mg SC every 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.

CLINICAL POLICY

Telotristat Ethyl

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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 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.

V. Dosage and Administration
Indication Dosing Regimen Maximum Dose Carcinoid syndrome diarrhea 250 mg PO TID 750 mg/day

VI. Product Availability
Tablet: 250 mg

CLINICAL POLICY

Telotristat Ethyl

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Reviews, Revisions, and Approvals Date P&T Approval Date 2Q 2022 annual review: no significant changes; references reviewed and updated. 02.14.22 05.22 Template changes applied to other diagnoses/indications and continued therapy section. 09.21.22

2Q 2023 annual review: no significant changes; added redirection to generic telotristat for brand Xermelo requests; updated Appendix C to include contraindication per PI; references reviewed and updated.
01.24.23 05.23 2Q 2024 annual review: no significant changes; added asterisk stating prior authorization may be required for SSA therapy; references reviewed and updated. 02.09.24 05.24 2Q 2025 annual review: no significant changes; updated Appendix B to show generic octreotide is available and lanreotide is available unbranded; references reviewed and updated. 01.29.25 05.25 Added step therapy bypass for IL HIM per IL HB 5395 06.27.25

2Q 2026 annual review: added failure of an SSA for IL HIM requests per prescribing information; in continued therapy, clarified examples of positive therapy; extended initial approval duration from 6 months to 12 months for this maintenance medication for a chronic condition; references reviewed and updated. Added ICHRA line of business. 03.31.26 05.26