Clinical Policy: Taliglucerase alfa (Elelyso) Reference Number: ERX.SPMN.138 Effective Date: 10/16 Coding Implications Last Review Date: 09/16 Revision Log

See Important Reminder at the end of this policy for important regulatory and legal information.

Policy/Criteria It is the policy of health plans affiliated with Envolve Pharmacy Solutions ® that taliglucerase alfa (ElelysoTM) is medically necessary when the following criteria are met:

I. Initial Approval Criteria A. Type 1 Gaucher disease (must meet all): 1. Age ≥ 4 years; 2. Diagnosis of type 1 Gaucher disease (GD1) confirmed by one of the following: a. Enzyme assay demonstrating a deficiency of β-glucocerebrosidase activity; b. DNA testing; 3. Therapeutic plan does not include concomitant use of Elelyso with Zavesca.

Approval duration: 6 months

B. Other diagnoses/indications: Refer to ERX.SPMN.16 - Global Biopharm Policy.

II. Continued Approval A. Type 1 Gaucher disease (must meet all): 1. Currently receiving medication via health plan benefit or member has previously met all initial approval criteria; 2. Therapeutic plan does not include concomitant use of Elelyso with Zavesca.

Approval duration: 12 months

B. Other diagnoses/indications (must meet 1 or 2): 1. Currently receiving medication via health plan benefit and documentation supports positive response to therapy; or 2. Refer to ERX.SPMN.16 - Global Biopharm Policy.

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Background Description/Mechanism of Action: Taliglucerase alfa, a hydrolytic lysosomal glucocerebroside-specific enzyme for intravenous infusion, is a recombinant active form of the lysosomal enzyme, β-glucocerebrosidase, which is expressed in genetically modified carrot plant root cells cultured in a disposable bioreactor system (ProCellEx®). β-Glucocerebrosidase (β-D-glucosyl-N-acylsphingosine glucohydrolase, E.C. 3.2.1.45) is a lysosomal glycoprotein enzyme that catalyzes the hydrolysis of the glycolipid glucocerebroside to glucose and ceramide. Taliglucerase alfa differs from native human glucocerebrosidase by two amino acids at the N terminal and up to 7 amino acids at the C terminal. Taliglucerase alfa is a glycosylated protein with oligosaccharide chains at the glycosylation sites having terminal mannose sugars. These mannose-terminated oligosaccharide chains of taliglucerase alfa are specifically recognized by endocytic carbohydrate receptors on macrophages, the cells that accumulate lipid in Gaucher disease.

Gaucher disease is an autosomal recessive disorder caused by mutations in the human glucocerebrosidase gene, which results in a reduced activity of the lysosomal enzyme glucocerebrosidase. Glucocerebrosidase catalyzes the conversion of the sphingolipid glucocerebroside into glucose and ceramide. The enzymatic deficiency results in accumulation of substrate glucocerebroside primarily in the lysosomal compartment of macrophages, giving rise to foam cells or "Gaucher cells," which accumulate in the liver, spleen and bone marrow. Elelyso, a long-term enzyme replacement therapy, is a recombinant analog of human lysosomal glucocerebrosidase that catalyzes the hydrolysis of glucocerebroside to glucose and ceramide, reducing the amount of accumulated glucocerebroside. Elelyso uptake into cellular lysosomes is mediated by binding of Elelyso mannose oligosaccharide chains to specific mannose receptors on the cell surface leading to internalization and subsequent transport to the lysosomes.

FDA Approved Indication(s): Elelyso is an enzyme / intravenous injection indicated for:  Type 1 Gaucher disease.

Appendices Appendix A: Abbreviation Key GD1: type 1 Gaucher disease

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Coding Implications Codes referenced in this clinical policy are for informational purposes only. Inclusion or exclusion of any codes does not guarantee coverage. Providers should reference the most up-to-date sources of professional coding guidance prior to the submission of claims for reimbursement of covered services. HCPCS Description Codes J3060 Injection, taliglucerase alfa, 10 units

Reviews, Revisions, and Approvals Date Approval Date Policy split from USS.SPMN.33 Lysosomal Storage Disorders and 08/16 09/16 converted to new template. Removed requirement for documentation of disease complications. Expanded diagnosis criteria to include option for DNA testing. Modified approval duration to 6 months for initial and 12 months for re-auth.

References 1. Elelyso Prescribing Information. New York, NY: Pfizer Laboratories Div Spectrum Pharmaceuticals, Inc.; November 2015. Available at http://www.elelyso.com. Accessed January 31, 2016. 2. Wynn R, Hahn S. Mucopolysaccharidoses: Clinical features and diagnosis. In: UpToDate, Waltham, MA: Walters Kluwer Health; 2016. Available at UpToDate.com. Accessed January 30, 2016. 3. Charrow J, Andersson HC, Kaplan P. Enzyme replacement therapy and monitoring for children with Type 1 Gaucher disease: consensus recommendations. J Pediatr. 2004; 144: 112-20. 4. Hollak, CEM, Weinreb NJ. The attenuated/late onset lysosomal storage disorders: therapeutic goals and indications for enzyme replacement treatment in Gaucher and Fabry disease. Best Pract Res Clin Endocrinol Metab. 2015; 29: 205-218.

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Important Reminder This clinical policy has been developed by appropriately experienced and licensed health care professionals based on a review and consideration of currently available generally accepted standards of medical practice; peer-reviewed medical literature; government agency/program approval status; evidence-based guidelines and positions of leading national health professional organizations; views of physicians practicing in relevant clinical areas affected by this clinical policy; and other available clinical information.

This Clinical Policy is not intended to dictate to providers how to practice medicine, nor does it constitute a contract or guarantee regarding payment or results. Providers are expected to exercise professional medical judgment in providing the most appropriate care, and are solely responsible for the medical advice and treatment of members.

This policy is the property of Envolve Pharmacy Solutions. Unauthorized copying, use, and distribution of this Policy or any information contained herein is strictly prohibited. By accessing this policy, you agree to be bound by the foregoing terms and conditions, in addition to the Site Use Agreement for Health Plans associated with Envolve Pharmacy Solutions.

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