CYSTAGON, Cysteamine Bitartrate Form

Cysteamine bitartrate (Cystagon®, Procysbi®) is a cysteine-depleting agent. FDA Approved Indication Cystagon and Procysbi are indicated for the treatment of nephropathic cystinosis. Cystagon is indicated for both children and adults, while Procysbi is indicated for patients 1 year 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 Cystagon and Procysbi are medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Nephropathic Cystinosis (must meet all):

1. Diagnosis of nephropathic cystinosis confirmed by one of the following (a, b, or c): a. Increased leukocyte cystine concentration (normal concentration: < 0.2 nmol half- cystine/mg protein); b. Cystinosin, lysosomal cystine transporter (CTNS) gene mutation; c. Corneal crystals on slit lamp examination;
2. If Procysbi is requested, member must use Cystagon, unless contraindicated or clinically significant adverse effects are experienced;
3. Dose does not exceed 1.95 g per m2 per day. Approval duration: 6 months 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: Page 1 of 6

   CLINICAL POLICY
   Cysteamine oral 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. Nephropathic Cystinosis (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. Member is responding positively to therapy as evidenced by improvement in the leukocyte cystine concentration within the past 3 months;
8. If request is for a dose increase, new dose does not exceed 1.95 g per m2 per day.
   Approval duration: 12 months B. Other diagnoses/indications (must meet 1 or 2):
9. 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

10. 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 policy – CP.CPA.09 for commercial, HIM. PA.154 for health insurance marketplace and CP.PMN.53 for Medicaid, or evidence of coverage documents.
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    CLINICAL POLICY
    Cysteamine oral IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key CTNS: cystinosin, lysosomal cystine transporter FDA: Food and Drug Administration WBC: white blood cell Appendix B: Therapeutic Alternatives
    Not applicable
    Appendix C: Contraindications/Boxed Warnings • Contraindication(s): hypersensitivity to penicillamine or cysteamine. • Boxed warning(s): none reported. Appendix D: General Information A clinical trial compared Cystagon and Procysbi in 43 (40 pediatric and 3 adult) patients with nephropathic cystinosis. Prior to randomization, patients were to be on a stable dose of Cystagon administered every six hours. This trial demonstrated that at steady-state, Procysbi administered every 12 hours was non-inferior to Cystagon administered every 6 hours with respect to the depletion of white blood cell (WBC) cystine concentrations. The least-square mean value of WBC cystine was 0.52 ± 0.06 nmol ½ cystine/mg protein after 12 hours under Procysbi and 0.44 ± 0.06 nmol ½ cystine/mg protein after 6 hours under Cystagon; a difference of 0.08 ± 0.03 nmol ½ cystine/mg protein (95.8% Confidence Interval = 0.01 to 0.15). The goal of cysteamine therapy is to lower WBC cystine levels. V. Dosage and Administration
    Indication Cystagon Procysbi Maximum Dose 1.95 g/m2/day 1.95 g/m2/day Dosing Regimen Initial: 1/4 to 1/6 of the maintenance dose
    Recommended maintenance dose:
    For age < 12 years: 1.30 g/m2/day given in four divided doses For age ≥ 12 years: 2.0 g/day in four divided doses Cysteamine-naïve patients: Initial: 1/4 to 1/6 of the maintenance dose
    Recommended maintenance dose: 1.3 g/m2/day given in two divided doses Switching from Cystagon: the starting total daily dose of Procysbi is equal to the previous total daily dose of Cystagon. Divide the total daily dose by two and administer every 12 hours. VI. Product Availability
    Drug Cystagon Availability
    Capsule: 50 mg, 150 mg Page 3 of 6

    CLINICAL POLICY
    Cysteamine oral Drug Procysbi Availability
    Delayed-release capsule: 25 mg, 75 mg Delayed-release oral granule packet: 75 mg, 300 mg VII.