Subject: Cystadane 2988-A SGM P2023

Drug

CYSTADANE  (betaine anhydrous)

Policy:

      I.  INDICATIONS

          The indications below including FDA-approved indications and
          compendial uses are considered a covered benefit provided that
          all the approval criteria are met and the member has no
          exclusions to the prescribed therapy.

 
          A.  FDA-Approved Indications
               Cystadane is indicated for the treatment of homocystinuria to
               decrease elevated homocysteine blood concentrations in
               pediatric and adult patients. Included within the category of
               homocystinuria are:
               1.  Cystathionine beta-synthase (CBS) deficiency
               2.  5,10-methylenetetrahydrofolate reductase (MTHFR)
                    deficiency
               3.  Cobalamin cofactor metabolism (cbl) defect

          B.  Compendial Use
               1.  Methylmalonic acidemia with homocystinuria

          All other indications are considered experimental/investigational
          and not medically necessary.

    II.  DOCUMENTATION

          Submission of the following information is necessary to initiate
          the prior authorization review:
          A.  For cystathionine beta-synthase (CBS) deficiency, enzyme
               analysis of CBS activity or genetic testing results
          B.  For 5,10-methylenetetrahydrofolate reductase (MTHFR)
               deficiency, enzyme analysis of MTHFR activity or genetic
               testing results
          C.  For cobalamin cofactor metabolism (cbl) defect, genetic
               testing results

   III.  CRITERIA FOR INITIAL APPROVAL

          A.  Homocystinuria
               Authorization of 12 months may be granted for treatment of
               homocystinuria to decrease elevated homocysteine blood
               levels when all of the following criteria are met:
               1.  The member has one of the following types of
                    homocystinuria and the diagnosis was confirmed by
                    enzyme assay or genetic testing:
                    i.     Cystathionine beta-synthase (CBS) deficiency
                    ii.    5,10-methylenetetrahydrofolate reductase (MTHFR)
                           deficiency
                    iii.   Cobalamin cofactor metabolism (cbl) defect
               2.  If the member has CBS deficiency, plasma methionine
                    concentrations will be monitored and kept below 1,000
                    micromol/L through dietary modification, and if
                    necessary, a reduction in Cystadane dose.

          B.  Methylmalonic acidemia with homocystinuria
               Authorization of 12 months may be granted for members
               who have a diagnosis of methylmalonic acidemia with
               homocystinuria.

 
   IV.  CONTINUATION OF THERAPY

          A.  Homocystinuria
               Authorization of 12 months may be granted for continued
               treatment in members requesting reauthorization for
               homocystinuria when both of the following criteria are met:
               1.  The total homocysteine level is undetectable or present
                    only in small amounts, OR there is a substantial decrease
                    in homocysteine levels and the dose will be increased
                    until maximum tolerability or plasma total homocysteine
                    is undetectable or present in only small amounts.
               2.  If the member has CBS deficiency, plasma methionine
                    concentrations will be monitored and kept below 1,000
                    micromol/L through dietary modification, and if
                    necessary, a reduction in Cystadane dose.

          B.  Methylmalonic acidemia with homocystinuria
               Authorization of 12 months may be granted for continued
               treatment in members requesting reauthorization for
               methylmalonic acidemia with homocystinuria who are
               experiencing benefit from therapy as evidenced by disease
               stability or disease improvement.

 

Place of Service:

Outpatient

The above policy is based on the following references:

1. Cystadane [package insert]. Lebanon, NJ: Recordati Rare Diseases, Inc.; October 2019.
2. Morris AA, Kožich V, Santra S, et al. Guidelines for the diagnosis and management of cystathionine beta-synthase deficiency. J Inherit Metab Dis. 2017;40(1):49-74. doi:10.1007/s10545-016-9979-0.
3. Clinical Consult: CVS Caremark Clinical Programs Review. Focus on Enzyme Disorder Clinical Program. September 2021.
4. Sloan JL, Carrillo N, Adams D, et al. Disorders of Intracellular Cobalamin Metabolism. 2008 Feb 25 [Updated 2022 Dec 28]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2021.
5. Genetic and Rare Diseases Information Center. List of FDA Orphan Drugs. Methylmalonic Acidemia. https://rarediseases.info.nih.gov/diseases/fda-orphan-drugs/M. Accessed December 28, 2022.
6. National Organization for Rare Disorders (2003). NORD guide to rare disorders. Philadelphia: Lippincott Williams & Wilkins. Methylmalonic Acidemia. https://rarediseases.org/rare-diseases/acidemia-methylmalonic/. Accessed December 28, 2022.

Copyright Aetna Inc. All rights reserved. Pharmacy Clinical Policy Bulletins are developed by Aetna to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. This Clinical Policy Bulletin contains only a partial, general description of plan or program benefits and does not constitute a contract. Aetna does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Aetna or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. This Clinical Policy Bulletin may be updated and therefore is subject to change.

June 18, 2023