Panobinostat (Farydak) Form

Panobinostat (Farydak®) is a histone deacetylase inhibitor. FDA Approved Indication(s) Farydak is indicated in combination with bortezomib and dexamethasone, for the treatment of patients with multiple myeloma (MM) who have received at least 2 prior regimens, including bortezomib and an immunomodulatory agent.
_ Secura Bio, Inc., manufacturer of Farydak, requested withdrawal of approval for the NDA for Farydak because the required post-marketing clinical trial was not feasible for them to complete (see Appendix D) 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 Farydak is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Multiple Myeloma (must meet all):

1. Diagnosis of MM;
   2. Prescribed by or in consultation with a hematologist or oncologist;
   3. Age ≥18 years;
   4. Failure of at least 2 prior regimens for MM including bortezomib and an immunomodulatory agent (e.g., dexamethasone), unless contraindicated or clinically significant adverse effects are experienced; *Prior authorization may be required for the 2 prior regimens

2. Farydak is prescribed in combination with bortezomib and dexamethasone; *Prior authorization may be required for these agents

   6. Request meets one of the following (a or b): a. Dose does not exceed six 20 mg doses per 21-day cycle for 16 cycles total; 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: Medicaid/HIM – 6 months Commercial – 12 months or duration of request, whichever is less Page 1 of 7

   CLINICAL POLICY Panobinostat B. Other diagnoses/indications (must meet 1 or 2):

3. 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
4. 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. Multiple Myeloma (must meet all):
5. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Farydak for a covered indication and has received this medication for at least 30 days;
6. Member is responding positively to therapy;
   3. If used in combination with bortezomib and dexamethasone, member has not received more than 16 cycles (48 weeks) of therapy;
7. If request is for a dose increase, request meets one of the following (a or b): a. New dose does not exceed six 20 mg doses per 21-day cycle for 16 cycles total; 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: Medicaid/HIM – 12 months Commercial – 12 months or duration of request, whichever is less B. Other diagnoses/indications (must meet 1 or 2):

8. 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: Page 2 of 7

   CLINICAL POLICY Panobinostat CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or

9. 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.
   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 FDA: Food and Drug Administration MM: multiple myeloma
   NCCN: National Comprehensive Cancer Network NDA: new drug application REMS: risk evaluation and mitigation strategy 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.
   Dosing Regimen Drug Name* Dose Limit/ Maximum Dose Varies Darzalex® (daratumumab) Doxil® (liposomal doxorubicin) Empliciti™
   (elotuzumab) Kyprolis®
   (carfilzomib) 16 mg/kg IV administered: As monotherapy or in combination with lenalidomide/ dexamethasone: weekly for weeks 1 to 8, then every 2 weeks for weeks 9 to 24, then every 4 weeks for week 25 onward until disease progression;
   In combination with bortezomib/dexamethasone: weekly for weeks 1 to 9, then every 3 weeks for weeks 10 to 24, then every 4 weeks for week 25 onward until disease progression. 30 mg/m2 IV over 1 hour on day 4 repeated every 3 weeks; used in combination with bortezomib. 10 mg/kg IV every week for the first two cycles, then every 2 weeks thereafter until disease progression; used in combination with lenalidomide and dexamethasone. 20 mg/m2 IV on two consecutive days each week for 3 weeks (Days 1, 2, 8, 9, 15 and 16) followed by a Page 3 of 7 Varies Varies Varies

   CLINICAL POLICY Panobinostat Drug Name Dosing Regimen Dose Limit/ Maximum Dose 12-day rest period (Days 17 to 28). For cycle 13 and beyond omit doses on days 8 and 9. Dexamethasone premedication is required for each Kyprolis dose in cycle 1. Each 28-day period is considered one treatment cycle. If tolerated in cycle 1, the dose should be escalated to 27 mg/m2 and in the subsequent cycles. 4 mg PO on Days 1, 8, and 15 of a 28-day cycle; used in combination with lenalidomide and dexamethasone 4 mg PO QD on days 1-21 of repeated 28-day cycles in combination with dixamethasone until disease progression. 25 mg PO QD on days 1-21 of repeated 28 day cycles in combination with dexamethasone. 1.3 mg/m2 IV bolus or SC twice weekly, with at least 72 hours between doses (on days 1, 4, 8, 11, 22, 25, 29, and 32), for cycles 1 to 4; then once weekly for 6 weeks (on days 1, 8, 22, and 29) for cycles 5 through 9. 4 mg/day 4 mg/day 25 mg/day Varies Ninlaro® (ixazomib) Pomalyst® (pomalidomide) Revlimid®
   (lenalidomide) bortezomib (Velcade®) 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. Examples Appendix C: Contraindications/Boxed Warnings • Contraindication(s): none reported • Boxed warning(s): severe diarrhea and cardiac toxicities o Because of these risks, Farydak has a risk evaluation and mitigation strategy (REMS) program that consists of a Medication Guide and a Dear Healthcare Professional Letter. Patient and physician enrollment in the manufacturer’s REMS program is required. Appendix D: General Information • Part of the initial accelerated approval of Farydak included a required post-marketing trial intended to verify the clinical benefit of Farydak. On November 22, 2021, Secura Bio, Inc. submitted a letter to the FDA requesting withdrawal of approval of the NDA for Farydak because it was not feasible for them to complete the required post-marketing clinical trials. On November 26, 2021, FDA acknowledged Secura Bio, Inc.'s request for withdrawal of approval of the NDA. As of March 24, 2022 the approval of Farydak is withdrawn. Page 4 of 7

   CLINICAL POLICY Panobinostat V. Dosage and Administration
   Indication Dosing Regimen MM 20 mg PO every other week for 3 doses per week (on Days 1, 3, 5, 8, 10, and 12) of Weeks 1 and 2 for each 21-day cycle for up to 8 cycles. Maximum Dose 20 mg/dose Consider continuing treatment for an additional 8 cycles for patients with clinical benefit who do not experience unresolved severe or medically significant toxicity (total treatment duration: up to 16 cycles [48 weeks]). _ The recommended dose of bortezomib is 1.3 mg/m2 given as an injection. The recommended dose of dexamethasone is 20 mg PO per scheduled day, on a full stomach. See Farydak Prescribing Information for cycle schedules. VI. Product Availability
   Capsules: 10 mg, 15 mg, 20 mg VII.