Palovarotene (Brand Name) Form

Palovarotene is a retinoic acid receptor (RAR)-γ agonist. FDA Approved Indication(s)
Palovarotene (Sohonos™) is indicated for reduction in the volume of new heterotopic ossification in adults and children aged 8 years and older for females and 10 years and older for males with fibrodysplasia ossificans progressiva (FOP). 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 Sohonos is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Fibrodysplasia Ossificans Progressiva (must meet all):

1. Diagnosis of FOP;
   2. Prescribed by or in consultation with a pediatric or adult orthopedics, orthopedic surgery, rheumatology, endocrinology, or metabolic disease specialist;
2. Age meets one of the following (a or b):
   a. For females: ≥ 8 years; b. For males: ≥ 10 years;
3. Presence of R206H ACVR1 mutation;
   5. Documentation of baseline HO volume assessed by low-dose whole body computed tomography (WBCT) scan, excluding the head;
4. Failure of both of the following at up to maximally indicated doses, unless clinically significant adverse effects are experienced or all are contraindicated (a and b): a. Prednisone used for flare-ups; b. Two nonsteroidal anti-inflammatory drugs (NSAIDs) between flare-ups;

5. Request meets both of the following (a and b): a. Dose does not exceed either of the following (i and ii): i. For chronic treatment, both of the following (1 and 2):
   1) 5 mg per day; 2) 1 capsule per day; ii. For flare-up treatment, both of the following (1 and 2):
   1) 20 mg per day for 4 weeks followed by 10 mg per day for 8 weeks; Page 1 of 7

   CLINICAL POLICY Palovarotene 2) 2 capsules per day for 4 weeks followed by 1 capsule per day for 8 weeks; b. Chronic treatment and flare-up treatment are not used concurrently. Approval duration:
   Chronic treatment – 6 months
   Flare-up treatment – 3 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 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
7. 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. Fibrodysplasia Ossificans Progressiva (must meet all):
8. 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);
9. One of the following (a or b):
   a. Member is responding positively to therapy as evidenced by one of the following (i, ii, or iii): i. Reduction in flare-ups from baseline; ii. Improvement in annualized new HO volume as assessed by low-dose WBCT scan; iii. Increased or stabilized mobility; b. Member has not received ≥ 18 months of Sohonos treatment;

10. Request meets both of the following (a and b): a. If request is for a dose increase, new dose does not exceed either of the following (i and ii): i. For chronic treatment, both of the following (1 and 2):
    1) 5 mg per day; 2) 1 capsule per day; Page 2 of 7

    CLINICAL POLICY Palovarotene ii. For flare-up treatment, both of the following (1 and 2):
    1) 20 mg per day for 4 weeks followed by 10 mg per day for 8 weeks; 2) 2 capsules per day for 4 weeks followed by 1 capsule per day for 8 weeks; b. Chronic treatment and flare-up treatment are not used concurrently. Approval duration:
    Chronic treatment – 12 months
    Flare-up treatment – 3 months B. Other diagnoses/indications (must meet 1 or 2):

11. 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

12. 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 FOP: fibrodysplasia ossificans progressiva
    HO: heterotopic ossification
    Appendix B: Therapeutic Alternatives
    Drug Name Dosing Regimen prednisone NSAIDs ibuprofen 2 mg/kg/day PO
    NSAID: nonsteroidal anti-inflammatory drug RAR: retinoic acid receptor WBCT: whole body computed tomography
    Dose Limit/ Maximum Dose 100 mg* Pediatrics: 4-10 mg/kg PO Q6H
    Adults: 200-800 mg PO Q6H
    Refer to dosing regimen Page 3 of 7

    CLINICAL POLICY Palovarotene Drug Name Dosing Regimen Dose Limit/ Maximum Dose Refer to dosing regimen indomethacin Pediatrics: 2-4 mg/kg/day PO or 150-200 mg/day (whichever is less), divided TID Adults: 50 mg PO TID Pediatrics and adults: 100-200 mg PO BID 600 mg/day celecoxib 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. Medications and doses recommended per the 2022 The International Clinical Council on FOP Medical Management guidelines Appendix C: Contraindications/Boxed Warnings • Contraindication(s): pregnancy, hypersensitivity to retinoids or any component of Sohonos
    • Boxed warning(s): embryo-fetal toxicity and premature epiphyseal closure in growing pediatric patients Appendix D: General Information
    • A flare-up is painful soft tissue swelling that may lead to extraskeletal HO
    • Flare-up symptoms include, but are not limited to pain, swelling, redness, decreased range of motion, stiffness, and warmth. V. Dosage and Administration
    Indication Dosing Regimen FOP Adults and pediatric patients ≥ 14 years:
    5 mg PO QD, with an increase in dose at the time of a flare-up to 20 mg PO QD for 4 weeks, followed by 10 mg PO QD for 8 weeks for a total of 12 weeks (20/10 mg flare-up treatment). Stop daily dosing when flare- up dosing begins.
    Maximum Dose Age ≥ 14 years: 20 mg/day Age < 14 years: 10 mg/day Pediatric patients < 14 years:
    Weight-adjusted for daily and flare-up dosing. Recommended dosage range from 2.5 to 5 mg PO QD. Stop daily dosing when flare-up dosing begins. Refer to table in Prescribing Information for complete pediatric dosing. VI. Product Availability
    Capsules: 1 mg, 1.5 mg, 2.5 mg, 5 mg, 10 mg VII.