Subject: Cystadane 2988-A SGM P2022

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. Sloan JL, Carrillo N, Adams D, et al. Disorders of Intracellular Cobalamin Metabolism. 2008 Feb 25 [Updated 2021 Dec 16]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2021.
4. 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 17, 2021.
5. 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 17, 2021.

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 26, 2022