Fosdenopterin (Nulibry™) is a cyclic pyranopterin monophosphate (cPMP) replacement therapy. FDA Approved Indication(s) Nulibry is indicated to reduce the risk of mortality in patients with molybdenum cofactor deficiency (MoCD) type A. 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 Nulibry is medically necessary when the following criteria are met:
I. Initial Approval Criteria A. Molybdenum Cofactor Deficiency Type A (must meet all):

1. One of the following (a or b): a. Diagnosis of MoCD type A confirmed by genetic testing (i.e., presence of molybdenum cofactor synthesis gene 1 [MOCS1] mutation) (see Appendix D); b. Age ≤ 28 days old, and diagnosis of MoCD type A is presumed based on onset of clinical and laboratory signs/symptoms consistent with MoCD type A (see Appendix D);
2. Prescribed by or in consultation with a neonatologist, neurologist, or specialist with expertise in the management of inborn errors of metabolism (e.g., pediatric geneticist);

3. Documentation of member’s current weight in kilograms;

   4. Dose does not exceed any of the following (a or b): a. Age < 1 year: the titration schedule as outlined in section V, then 0.9 mg/kg per day (see Appendix E for vial quantity recommendations); b. Age ≥ 1 year: 0.9 mg/kg per day (see Appendix E for vial quantity recommendations). Approval duration:
      Genetically confirmed diagnosis – 6 months Presumptive diagnosis – 1 month Page 1 of 7

   CLINICAL POLICY Fosdenopterin 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
5. 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. Molybdenum Cofactor Deficiency Type A (must meet all):
6. 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);
7. If the diagnosis of MoCD type A was presumptive at the time of initial authorization, it has since been confirmed by genetic testing (i.e., presence of MOCS1 mutation) (see Appendix D);
8. Member is responding positively to therapy as evidenced by, including but not limited to, improvement in any of the following parameters: a. Clinical outcomes, such as: improved symptoms, achievement of motor milestones, decreased seizure activity, lack of clinical deterioration (e.g., no progression to severe epileptic encephalopathy);
   b. Biochemical outcomes, such as: decreased or normalized urinary s-sulfocysteine (SSC) or xanthine levels, increased or normalized uric acid levels;
9. Documentation of member’s current weight in kilograms;
   5. If request is for a dose increase, new dose does not exceed 0.9 mg/kg per day (see Appendix E for vial quantity recommendations). Approval duration: 12 months B. Other diagnoses/indications (must meet 1 or 2):

10. 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): Page 2 of 7

    CLINICAL POLICY Fosdenopterin 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

11. 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; B. MoCD type B. IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key cPMP: cyclic pyranopterin monophosphate FDA: Food and Drug Administration MoCD: molybdenum cofactor deficiency Appendix B: Therapeutic Alternatives
    Not applicable Appendix C: Contraindications/Boxed Warnings None reported MOCS1: molybdenum cofactor synthesis gene 1 SSC: s-sulfocysteine Appendix D: General Information • A list of available genetic tests for MoCD type A can be found here: https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=C1854988&filter=testtype:clinical.
    • Clinical and laboratory signs/symptoms consistent with MoCD type A include, but are not limited to: seizures, exaggerated startle response, high-pitched cry, axial hypotonia, limb hypertonia, feeding difficulties, elevated urinary sulfite and/or SSC, elevated xanthine in urine or blood, low or absent uric acid in the urine or blood. Appendix E: Vial Quantity Recommendations The below recommendations are based on average weight (50th percentile) by age according to WHO and CDC growth charts. Members whose actual body weight exceeds the average weight should be approved for the appropriate number of vials required to achieve the desired dose. Page 3 of 7

    CLINICAL POLICY Fosdenopterin Age Range 0 to < 1 year 1 to < 5 years 5 to < 8 years 8 to < 11 years 11 to < 13 years 13 to < 15 years 15 to < 17 years 17 to 20 years

    Vials/Day

    1 2 3 4 5 6 7 8 V. Dosage and Administration Indication Dosing Regimen MoCD type A Titration schedule for age < 1 year: Maximum Dose 0.9 mg/kg/day • Preterm neonates (gestational age < 37 weeks):
    o Initial dosage: 0.4 mg/kg IV QD o Month 1: 0.7 mg/kg IV QD o Month 3: 0.9 mg/kg IV QD • Term neonates (gestational age ≥ 37 weeks):
    o Initial dosage: 0.55 mg/kg IV QD o Month 1: 0.75 mg/kg IV QD o Month 3: 0.9 mg/kg IV QD Age ≥ 1 year: 0.9 mg/kg IV QD
    VI. Product Availability Lyophilized powder or cake in a single-dose vial for reconstitution: 9.5 mg VII.