Sunflower Health Plan CRYSVITA, Burosumab-twza Form

Burosumab-twza (Crysvita®) is a fibroblast growth factor 23 (FGF23) blocking antibody. FDA Approved Indication(s) Crysvita is indicated for the treatment of: • X-linked hypophosphatemia (XLH) in adult and pediatric patients 6 months of age and older. • FGF23-related hypophosphatemia in tumor-induced osteomalacia (TIO) associated with phosphaturic mesenchymal tumors that cannot be curatively resected or localized in adult and pediatric patients 2 years of age and older. 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 Crysvita is medically necessary when the following criteria are met: I. Initial Approval Criteria A. X-Linked Hypophosphatemia (must meet all): 1. Diagnosis of XLH confirmed by one of the following (a or b): a. DNA testing confirms the presence of mutations in the PHEX gene; b. Elevated serum FGF23 levels; 2. Prescribed by or in consultation with an endocrinologist or metabolic disease specialist; 3. Age ≥ 6 months; 4. Current (within the last 30 days) serum phosphorus levels are one of the following (a or b): a. Below the reference range for age and gender (use laboratory-specific reference ranges if available; otherwise, see Appendix D for ranges), and member has not received oral phosphate or vitamin D replacement therapy and serum phosphorus; b. In normal range, but member remains symptomatic (e.g., rickets, growth impairment, musculoskeletal pain, bone fractures) despite currently receiving oral phosphate and/or vitamin D replacement therapy; 5. Presence of clinical signs and symptoms of the disease (e.g., rickets, growth impairment, musculoskeletal pain, bone fractures); 6. Crysvita is not prescribed concurrently with oral phosphate or vitamin D replacement therapy; Page 1 of 8 CLINICAL POLICY Burosumab-twza 7. Dose does not exceed one of the following (a or b): a. Age 6 months to < 18 years: 2 mg/kg up to 90 mg every two weeks; b. Age ≥ 18 years: 1 mg/kg up to 90 mg every four weeks. Approval duration: Medicaid/HIM – 6 months Commercial – 6 months or to the member’s renewal date, whichever is longer B. Tumor-Induced Osteomalacia (must meet all): 1. Diagnosis of TIO with confirmed elevated serum FGF23 levels; 2. Prescribed by or in consultation with an endocrinologist or metabolic disease specialist; 3. Age ≥ 2 years; 4. Failure of a ≥ 3 consecutive month trial of oral phosphate and vitamin D replacement therapy, unless contraindicated or clinically significant adverse effects are experienced; 5. Current (within the last 30 days) serum phosphorus levels are one of the following (a or b): a. Below the reference range for age and gender (use laboratory-specific reference ranges if available; otherwise, see Appendix D for ranges), and member has not received oral phosphate or vitamin D replacement therapy; b. In normal range, but member remains symptomatic (e.g., osteomalacia, muscle weakness, fatigue, bone pain, fractures) despite currently receiving oral phosphate and/or vitamin D replacement therapy; 6. Documentation confirms that the causative tumor(s) is/are not amenable to surgical excision or resection; 7. Crysvita is not prescribed concurrently with oral phosphate or vitamin D replacement therapy; 8. Documentation of member’s current weight, for dose calculation purposes; 9. Dose does not exceed 2 mg/kg (maximum of 180 mg) every two weeks. Approval duration: Medicaid/HIM – 6 months Commercial – 6 months or to the member’s renewal date, whichever is longer C. 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 Page 2 of 8 CLINICAL POLICY Burosumab-twza 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. X-Linked Hypophosphatemia (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 both of the following (a and b): a. An increase in serum phosphorus levels from baseline and/or maintenance within the normal range for age and gender, not to exceed the upper limit of that normal range (use laboratory-specific reference ranges if available; otherwise, see Appendix D for ranges); b. A positive clinical response including any of the following: enhanced height velocity, improvement in skeletal deformities, reduction of fractures, reduction of generalized bone pain; 3. If request is for a dose increase, new dose does not exceed one of the following (a or b): a. Age 6 months to < 18 years: 2 mg/kg up to 90 mg every two weeks; b. Age ≥ 18 years: 1 mg/kg up to 90 mg every four weeks. Approval duration: Medicaid/HIM – 12 months Commercial – 6 months or to member’s renewal date, whichever is longer B. Tumor-Induced Osteomalacia (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 both of the following (a and b): a. An increase in serum phosphorus levels from baseline and/or maintenance within the normal range for age and gender, not to exceed the upper limit of that normal range (use laboratory-specific reference ranges if available; otherwise, see Appendix D for ranges); b. Documentation confirms improvement in symptoms (e.g., osteomalacia, muscle weakness, fatigue, bone pain, fractures); Page 3 of 8 CLINICAL POLICY Burosumab-twza 3. Documentation of member’s current weight, for dose calculation purposes; 4. If request is for a dose increase, new dose does not exceed 2 mg/kg (maximum of 180 mg) every two weeks. Approval duration: Medicaid/HIM – 12 months Commercial – 6 months or to member’s renewal date, whichever is longer C. 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, CP.PMN.53 for Medicaid, or evidence of coverage documents. IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key FDA: Food and Drug Administration FGF23: fibroblast growth factor 23 Appendix B: Therapeutic Alternatives Not applicable TIO: tumor-induced osteomalacia XLH: X-linked hypophosphatemia Appendix C: Contraindications/Boxed Warnings • Contraindication(s): concomitant use with oral phosphates and active vitamin D analogs, initiation of Crysvita therapy when serum phosphorus is within or above the normal range for age, severe renal impairment or end stage renal disease because these conditions are associated with abnormal mineral metabolism. • Boxed warning(s): none reported Page 4 of 8 CLINICAL POLICY Burosumab-twza Appendix D: General Information • Laboratory-specific reference ranges for serum phosphorus levels should be used when available; otherwise, the age- and gender-based reference ranges found below may be used: Females 1-7 years: 4.3-5.4 mg/dL 8-13 years: 4.0-5.2 mg/dL 14-15 years: 3.5-4.9 mg/dL 16-17 years: 3.1-4.7 mg/dL ≥ 18 years: 2.5-4.5 mg/dL Males 1-4 years: 4.3-5.4 mg/dL 5-13 years: 3.7-5.4 mg/dL 14-15 years: 3.5-5.3 mg/dL 16-17 years: 3.1-4.7 mg/dL ≥ 18 years: 2.5-4.5 mg/dL • For pediatric patients continuing on Crysvita therapy, if serum phosphorus is > 5 mg/dL, it is recommended to withhold the dose until the serum phosphorus level falls below the reference range per age. • For adult patients continuing on Crysvita therapy, if serum phosphorus is above the upper limit of the normal range, it is recommended to withhold the dose until the serum phosphorus level falls below the reference range. V. Dosage and Administration Indication Dosing Regimen XLH Pediatric XLH • Weight < 10 kg: 1 mg/kg rounded to the nearest 1 mg, SC every two weeks • Weight ≥ 10 kg: 0.8 mg/kg rounded to the nearest 10 mg, SC every two weeks Increase dose up to approximately 2 mg/kg, SC every two weeks to achieve normal serum phosphorus. Adult XLH 1 mg/kg body weight rounded to the nearest 10 mg SC every four weeks. Crysvita should only be administered by a healthcare professional. Pediatric TIO (2 years and older) • Starting dose is 0.4 mg/kg of body weight rounded to the nearest 10 mg SC every two weeks • Dose may be increased up to 2 mg/kg Adult TIO • Starting dose is 0.5 mg/kg SC every four weeks • Dose may be increased up to 2 mg/kg TIO VI. Product Availability Single-dose vials for injection: 10 mg/mL, 20 mg/mL, 30 mg/mL Maximum Dose Pediatric XLH: 2 mg/kg up to 90 mg every two weeks Adult XLH: 1 mg/kg up to 90 mg every four weeks 180 mg, administered every two weeks Page 5 of 8 CLINICAL POLICY Burosumab-twza VII.