Baloxavir Marboxil (Xofluza) Form

Baloxavir marboxil (Xofluza®) is an antiviral polymerase acidic (PA) endonuclease inhibitor. FDA Approved Indication(s) Xofluza is indicated for: • Treatment of acute uncomplicated influenza in patients 5 years of age and older who have been symptomatic for no more than 48 hours and who are otherwise healthy or at high risk of developing influenza-related complications. • Post-exposure prophylaxis of influenza in patients 5 years of age and older following contact with an individual who has influenza. Limitation(s) of use: Influenza viruses change over time, and factors such as the virus type or subtype, emergence of resistance, or changes in viral virulence could diminish the clinical benefit of antiviral drugs. Consider available information on drug susceptibility patterns for circulating influenza virus strains when deciding whether to use Xofluza. 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 Xofluza is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Influenza Treatment and Post-Exposure Prophylaxis (must meet all):

1. Request is for influenza treatment or post-exposure prophylaxis;
2. Age ≥ 5 years;
3. Member must use oseltamivir, unless one of the following applies (a, b, c, d, or e): a. Laboratory confirmation of influenza B infection (e.g., member, close contact); b. High prevalence of influenza B circulation in the community; c. Oseltamivir community resistance in the current influenza season; d. Prior oseltamivir administration in the current influenza season; e. Oseltamivir contraindications or history of clinically significant adverse effects;
   4. For oral suspension requests, member is unable to swallow tablets, has difficulty swallowing tablets, or requires enteral administration;

4. Dose does not exceed one of the following (a, b, or c): a. Weight < 20 kg (i and ii): Page 1 of 8

   CLINICAL POLICY Baloxavir Marboxil i. 2 mg/kg once; ii. 1 bottle once; b. Weight 20 kg to < 80 kg (i and ii):
   i. 40 mg once; ii. 1 tablet or 1 bottle once; c. Weight ≥ 80 kg (i and ii):
   i. 80 mg once; ii. 1 tablet or 2 bottles once.
   Approval duration: 4 weeks (one dose only) 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. Influenza Treatment and Post-Exposure Prophylaxis
   3. Re-authorization is not permitted. Members must meet the initial approval criteria. Approval duration: Not applicable B. Other diagnoses/indications (must meet 1 or 2):
   4. 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 Baloxavir Marboxil

   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 CDC: Centers for Disease Control and Prevention
      FDA: Food and Drug Administration IDSA: Infectious Diseases Society of America PA: polymerase acidic 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 oseltamivir (Tamiflu®) Dose Limit/ Maximum Dose 150 mg/day Influenza Treatment1 • Pediatrics Dosing Regimen o Infants, pre-term and term: weight-based dosing ranging from 1 mg/kg to 3 mg/kg PO BID for 5 days
      o Age 1 to 12 years: weight-based dosing ranging from 30 mg to 75 mg PO BID for 5 days • Adults and adolescents o Age ≥ 13 years: 75 mg PO BID for 5 days Influenza Prophylaxis1 • Pediatrics o Age 3 months to 8 months: 3 mg/kg PO QD. Duration of therapy is dependent on the type of exposure.
      o Age 9 months to 11 months: 3.5 mg/kg PO QD. Duration of therapy is dependent on the type of exposure. o Age 1 to 12 years: Weight-based dosing ranging from 30 mg to 75 mg PO QD for 10 days • Adults and adolescents o Age ≥ 13 years: 75 mg PO QD for 10 days Page 3 of 8

   CLINICAL POLICY Baloxavir Marboxil Drug Name Dosing Regimen Dose Limit/ Maximum Dose • Community outbreak
   o Age 1 to 12 years: Weight-based dosing ranging from 30 mg to 75 mg PO QD for up to 6 weeks o Age ≥ 13 years: 75 mg PO QD for up to 6 weeks ___ See also CDC/IDSA and American Academy of Pediatrics influenza resources for guidance. 1 Oral oseltamivir phosphate is approved by the FDA for treatment of acute uncomplicated influenza within 2 days of illness onset in people 14 days and older, and for chemoprophylaxis in people 1 year and older. Although not part of the FDA-approved indications, use of oral oseltamivir for treatment of influenza in infants less than 14 days old, and for chemoprophylaxis in infants 3 months to 1 year, is recommended by the CDC and the American Academy of Pediatrics.
   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): history of hypersensitivity to baloxavir marboxil or any of its ingredients • Boxed warning(s): none reported Appendix D: High Risk Factors for Developing Influenza-Related Complications Per the Centers for Disease Control and Prevention, the following are health factors known to increase the risk of developing serious complications from influenza: • Age ≥ 65 years • Children younger than 2 years old • Asthma • Neurologic and neurodevelopment conditions • Blood disorders (such as sickle cell disease) • Chronic lung disease (such as chronic obstructive pulmonary disease [COPD] and cystic fibrosis) • Endocrine disorders (such as diabetes mellitus) • Heart disease (such as congenital heart disease, congestive heart failure and coronary artery disease) • Kidney diseases • Liver disorders • Metabolic disorders (such as inherited metabolic disorders and mitochondrial disorders) • People who are obese with a body mass index (BMI) of 40 kg/m2 or higher • People younger than 19 years old on long-term aspirin- or salicylate-containing medications. Page 4 of 8

   CLINICAL POLICY Baloxavir Marboxil • People with a weakened immune system due to disease (such as people with HIV or AIDS, or some cancers such as leukemia) or medications (such as those receiving chemotherapy or radiation treatment for cancer, or persons with chronic conditions requiring chronic corticosteroids or other drugs that suppress the immune system) • People who have had a stroke • Pregnant people and people up to 2 weeks after the end of pregnancy • People who live in nursing homes and other long-term care facilities • People from certain racial and ethnic minority groups are at increased risk for hospitalization with flu, including non-Hispanic Black persons, Hispanic or Latino persons, and American Indian or Alaska Native persons V. Dosage and Administration
   Indication Influenza treatment or post-exposure prophylaxis Dosing Regimen Adults and pediatric patients ≥ 5 years: • Weight < 20 kg (oral suspension only): 2 Maximum Dose 80 mg once mg/kg PO once • Weight 20 kg to < 80 kg (oral suspension or tablets): 40 mg PO once • Weight ≥ 80 kg (oral suspension or tablets): 80 mg PO once VI. Product Availability
   • Tablets: 40 mg, 80 mg • Oral suspension: 40 mg/20 mL (2 mg/mL; 20 mL bottle) VII.