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Medical Policy

Policy Num:       08.001.023
Policy Name:     ERWINAZE 
Policy ID:          [08.001.023][Ar L M+ P+][0.00.00]

Last Review:       November 10, 2021
Next Review:      N/A
Issue:                   November, 2021

Archived

Related Policies: None

ERWINAZE 

Summary

Asparagine is an amino acid essential for cell growth. It occurs in most cells. The neoplastic cells present in acute lymphocytic leukemia lack the enzyme that synthesizes asparagine, therefore these neoplastic cells use circulating asparagine in the blood for their growth. L-asparaginase is an enzyme that reduces levels of circulating asparagine in the blood, thus depriving the asparagine available to the neoplastic cells, thus inhibiting their growth.

Objective

The objective of this evidenced based review is discussion of Erwinaze for the treatment of patients with acute lymphoblastic leukemia (ALL) who have developed hypersensitivity to E. coli-derived asparaginase.

Policy Statements

ERWINAZE is considered for payment in the treatment of acute lymphocytic leukemia and acute myeloid leukemia according to established protocols.

Policy Guidelines

Erwinaze may be considered medically necessary for the treatment of patients with acute lymphoblastic leukemia (ALL) who have developed hypersensitivity to E. coli-derived asparaginase. Erwinaze is considered investigational when used for the treatment the treatment of patients with acute lymphoblastic leukemia (ALL) who have not developed hypersensitivity to E. coli derived asparaginase.

Benefit Application

BlueCard/National Account Issues

N/A

Background

There are different types of L-asparaginase available, each derived from a different bacterium. It can be obtained from E.coli and Erwinia chrysanthemi. These enzymes are immunologically distinct and there are no cross-reactions. Patients who develop hypersensitivity to E. coli do not necessarily develop the E. chrysanthemy enzyme.

ERWINAZE, in combination with other antineoplastic drugs, is used for the treatment of acute lymphocytic leukemia (ALL) and other conditions where asparaginase deprivation can result in a useful effect. The possible side effects are: depression, pancreatitis, fever, nausea and vomiting, anaphylaxis, alteration of liver tests, urticaria, coagulopathies. Its use is contraindicated in patients with allergies to this medicine or its components and in pregnant or lactating women.

Regulatory Status

ERWINAZE is considered an orphan drug. An Orphan Drug is a medicine for rare diseases and whose market is a small one. The Orphan Drug Act of January 1983 was approved at the request of the "National Organization for Rare Disorders". A rare disease is considered to be one with an incidence of less than 200,000 people in the United States.

Rationale

Erwinaze (asparaginase Erwinia chrysanthemi) is an asparagine-specific enzyme. L-asparaginase is a tetrameric enzyme consisting of four identical subunits, each having a molecular weight of about 35 kDa. Asparaginase Erwinia chrysanthemi catalyzes the deamidation of asparagine to aspartic acid and ammonia, resulting in a reduction in circulating levels of asparagine. The mechanism of action of Erwinaze is thought to be based on the inability of leukemic cells to synthesize asparagine due to lack of asparagine synthetase activity, resulting in cytotoxicity specific for leukemic cells that depend on an exogenous source of the amino acid asparagine for their protein metabolism and survival.(1) Erwinaze (asparaginase Erwinia chrysanthemi) is indicated for the treatment of patients with acute lymphoblastic leukemia (ALL) who have developed hypersensitivity to E. coli-derived asparaginase as a component of a multiagent chemotherapeutic regimen.

Population Reference No. 1 Policy Statement

For individuals with acute lymphocytic leukemia who have developed hypersensitivity to E. coli-derived asparaginase.            Interventions of interest are L-asparaginase as a component of muli-agent chemotherapy regimens.  Comparators of interests are when not used with multi-agent chemotherapy regimens. Relevant outcomes include inhibition of neoplastic cells growth.  The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

Supplemental Information

Erwinaze is contraindicated in patients with a history of pancreatitis, thrombosis, hemorrhagic events or anaphylaxis reaction with prior L-asparaginase therapy. Discontinue Erwinaze in the event of serious hypersensitivity reactions, including anaphylaxis, and severe or hemorrhagic pancreatitis. Glucose intolerance can occur and, in some cases, may be irreversible. Perform appropriate monitoring and treat hyperglycemia with insulin, as necessary. If thrombosis or hemorrhage occurs discontinue Erwinaze until resolved. Use in pregnant women only if clearly needed. Do not use in lactating women.(2)

Practice Guidelines and Position Statements

N/A

Medicare National Coverage

N/A

References

1.    The Medicines.org.uk website – www.medicines.org.uk (November 2008).
2.    MEDLINE 17695416
3.    EUSA Pharma: http://www.eusapharma.com/erwinase.html 
4.    Asselin BL, Whitin JC, Cappola DJ, et al, “Comparative Pharmacokinetic Studies of Three 
5.    Asparaginase Preparations,” J Clin Oncol, 1993, 11(9):1780-6. [PubMed 8355045]
6.    Avramis VI and Panosyan EH, “Pharmacokinetic/Pharmacodynamic Relationships of Asparaginase Formulations: The Past, the Present and Recommendations for the Future,” Clin Pharmacokinet, 2005, 44(4):367-93. [PubMed 15828851]
7.    Duval M, Suciu S, Ferster A, et al, “Comparison of Escherichia Coli -Asparaginase With Erwinia-Asparaginase in the Treatment of Childhood Lymphoid Malignancies: Results of a Randomized European Organisation for Research and Treatment of Cancer − Children's Leukemia Group Phase 3 Trial,” Blood, 2002, 99(8):2734-9.
8.    Schrey D, Speitel K, Lanvers-Kaminsky C, et al, “Five-Year Single-Center Study of Asparaginase Therapy Within the ALL-BFM 2000 Tri8.01.24al,” Pediatr Blood Cancer, 2011, 57(3):378-84. [PubMed 21337682]
9.    Erwinaze (asparaginase) [prescribing information]. Palo Alto, CA: Jazz Pharmaceuticals; March 2016.

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Policy History