Sunflower Health Plan OXBRYTA, Voxelotor Form

Voxelotor (Oxbryta™) is a hemoglobin S (HbS) polymerization inhibitor. FDA Approved Indication(s) Oxbryta is indicated for the treatment of sickle cell disease (SCD) in adults and pediatric patients 4 years of age and older. This indication is approved under accelerated approval based on the increase in hemoglobin (Hb). Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s). 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 Oxbryta is medically necessary when the following criteria are met: I. Initial Approval Criteria A. Sickle Cell Disease (must meet all): 1. Diagnosis of SCD with one of the following genotypes (a, b, c, or d): a. Homozygous hemoglobin S; b. Hemoglobin Sβ0‑thalassemia; c. Hemoglobin Sβ+‑thalassemia; d. Hemoglobin SC; 2. Age ≥ 4 years; 3. Prescribed by or in consultation with a hematologist; 4. Hb level ≥ 5.5 and ≤ 10.5 g/dL; 5. Member meets one of the following (a or b): a. Member has experienced at least 1 vaso-occlusive crisis (VOC) within the past 6 months while on hydroxyurea at up to maximally indicated doses (see Appendix D); b. Member has intolerance* or contraindication to hydroxyurea and has experienced at least 1 VOC within the past 12 months (see Appendix D); *Myelosuppression and hydroxyurea treatment failure: Myelosuppression is dose-dependent and reversible and does not qualify for treatment failure. NIH guidelines recommend a 6 month trial on the maximum tolerated dose prior to considering discontinuation due to treatment failure, whether due to lack of adherence or failure to respond to therapy. A lack of increase in mean Page 1 of 8 CLINICAL POLICY Voxelotor corpuscular volume (MCV) and/or fetal hemoglobin (HbF) levels is not indication to discontinue therapy. 6. If request is for tablets for oral suspension, documentation supports inability to swallow tablets; 7. For age ≥ 5 years: Failure of L-glutamine at up to maximally tolerated doses, unless contraindicated or clinically significant adverse effects are experienced; 8. Failure of blood transfusion(s), unless contraindicated or clinically significant adverse effects are experienced (e.g., cutaneous ulcers, iron overload); 9. Oxbryta is prescribed concurrently with hydroxyurea, unless contraindicated or clinically significant adverse effects are experienced; 10. Oxbryta is not prescribed concurrently with Adakveo; 11. Dose does not exceed one of the following (a, b, or c): a. Member is concurrently taking a strong CYPA3A4 inducer (see Appendix D): 2,500 mg (5 tablets) per day; b. Member is concurrently taking a moderate CYPA3A4 inducer (see Appendix D): 2,000 mg (4 tablets) per day; c. For all other members: 1,500 mg (3 tablets) per day; Approval duration: 2 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, 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 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. Sickle Cell Disease (must meet all): 1. 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 as evidenced by an increase in Hb level from baseline of at least 1 g/dL; Page 2 of 8 CLINICAL POLICY Voxelotor 3. Oxbryta is prescribed concurrently with hydroxyurea, unless contraindicated or clinically significant adverse effects are experienced; 4. Oxbryta is not prescribed concurrently with Adakveo; 5. If request is for a dose increase, new dose does not exceed one of the following (a, b, or c): a. Member is concurrently taking a strong CYPA3A4 inducer (see Appendix D): 2,500 mg (5 tablets) per day; b. Member is concurrently taking a moderate CYPA3A4 inducer (see Appendix D): 2,000 mg (4 tablets) per day; c. For all other members: 1,500 mg (3 tablets) per day. Approval duration: 6 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, 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 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. 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 Hb: hemoglobin SCD: sickle cell disease VOC: vaso-occlusive crisis 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. Page 3 of 8 CLINICAL POLICY Voxelotor Drug Name Dosing Regimen hydroxyurea (Droxia) hydroxyurea (Siklos) L-glutamine (Endari) Age ≥ 18 years Initial: 15 mg/kg/day PO single dose; based on blood counts, may increase by 5 mg/kg/day every 12 weeks to a max 35 mg/kg/day Age ≥ 2 years Initial: 20 mg/kg/day PO QD; based on blood counts, may increase by 5 mg/kg/day every 8 weeks or if a painful crisis occurs Weight > 65 kg: 15 g (3 packets) PO BID Weight 30 to 65 kg: 10 g (2 packets) PO BID Weight < 30 kg: 5 g (1 packet) PO BID Dose Limit/ Maximum Dose 35 mg/kg/day 35 mg/kg/day 30 g/day (maximum dose based on weight) 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): prior drug hypersensitivity to Oxbryta or excipients • Boxed warning(s): none reported Appendix D: General Information • A VOC is defined as a previously documented episode of acute painful crisis or acute chest syndrome (ACS) for which there was no explanation other than VOC that required prescription or healthcare professional-instructed use of analgesics for moderate to severe pain. • Myelosuppression and hydroxyurea treatment failure: Myelosuppression is dose- dependent and reversible and does not qualify for treatment failure. NIH guidelines recommend a 6 month trial on the maximum tolerated dose prior to considering discontinuation due to treatment failure, whether due to lack of adherence or failure to respond to therapy. A lack of increase in mean corpuscular volume (MCV) and/or fetal hemoglobin (HbF) levels is not indication to discontinue therapy. • Hydroxyurea dose titration: Members should obtain complete blood counts (CBC) with white blood cell (WBC) differential and reticulocyte counts at least every 4 weeks for titration. The following lab values indicate that it is safe to increase dose. o Absolute neutrophil count (ANC) in adults ≥ 2,000/uL, or ANC ≥ 1,250/uL in younger patients with lower baseline counts o Platelet counts ≥ 80,000/uL If neutropenia or thrombocytopenia occurs: hydroxyurea dosing is held, CBC and WBC differential are monitored weekly, members can restart hydroxyurea when values have recovered. • Examples of moderate CYP3A4 inducers: bosentan, dabrafenib, efavirenz, mitapivat, modafinil, rifabutin, rifapentine • Examples of strong CYP3A4 inducers: apalutamide, carbamazepine, phenobarbital, phenytoin, rifampin • Rationale for the failure of L-glutamine and blood transfusions prior to Oxbryta use: Oxbryta’s lack of achieving clinically meaningful endpoints is the rationale for the Page 4 of 8 CLINICAL POLICY Voxelotor redirection to agents that do demonstrate clinically meaningful endpoints. While Oxbryta has demonstrated a statistically significant increase of 1.1 g/dL Hb and reduction in hemolysis markers, it’s not clear that improved levels of hemoglobin lead to any clinically significant endpoints. There is uncertainty of whether there is a threshold of reduced hemolysis required to achieve clinical benefit. Additionally, the pivotal trial demonstrated that although hemoglobin levels increased with treatment, the rate of pain crises did not decrease. Currently there is no compelling data to support that an increase of 1.1 g/dL hemoglobin level results in a reduction in VOCs or other clinically meaningful outcomes related to SCD. o L-glutamine has demonstrated statistically significant reduced acute pain episodes, delay in time to first crisis was delayed, and reduced hospitalizations. o Blood transfusions lower the percentage of sickle Hb and increase Hgb oxygen saturation, both of which decrease the propensity for vaso-occlusion and decrease the incidence of SCD-related complications. • STAND trial results for Adakveo: In a press release Novartis announced that the STAND study did not demonstrate a statistically significant difference between Adakveo 5mg/kg or Adakveo 7.5mg/kg and placebo in annualized rates of VOCs leading to a healthcare visit over the first-year post randomization. These findings are inconsistent with previous trial results from SUSTAIN, which demonstrated the superiority of crizanlizumab 5.0mg/ kg compared to placebo. V. Dosage and Administration Maximum Dose See regimen Indication SCD Dosing Regimen Age ≥ 12 years 1,500 mg PO QD with or without food. Strong CYP3A4 inducer: 2500 mg PO QD Moderate CYP3A4 inducer: 2000 mg PO QD Age 4 to < 12 years Weight ≥ 40 kg: 1500 mg PO QD • Strong CYP3A4 inducer: 2500 mg PO QD • Moderate CYP3A4 inducer: 2000 mg PO QD Weight 20 kg to < 40 kg: 900 mg PO QD • Strong CYP3A4 inducer: 1500 mg PO QD • Moderate CYP3A4 inducer: 1200 mg PO QD Weight 10 kg to < 20 kg: 600 mg PO QD • Strong or moderate CYP3A4 inducer: 900 mg PO QD VI. Product Availability • Tablets: 300 mg, 500 mg • Tablet for oral suspension: 300 mg Page 5 of 8 CLINICAL POLICY Voxelotor VII.