Notification



Notification Issue Date:



Medical Policy Bulletin


Title:Asparaginase Erwinia Chrysanthemi (Erwinaze®)

Policy #:08.01.35a

This policy is applicable to the Company’s commercial products only. Policies that are applicable to the Company’s Medicare Advantage products are accessible via a separate Medicare Advantage policy database.


The Company makes decisions on coverage based on Policy Bulletins, benefit plan documents, and the member’s medical history and condition. Benefits may vary based on contract, and individual member benefits must be verified. The Company determines medical necessity only if the benefit exists and no contract exclusions are applicable.

When services can be administered in various settings, the Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition. This decision is based on the member’s current medical condition and any required monitoring or additional services that may coincide with the delivery of this service.

This Medical Policy Bulletin document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy Bulletin will be reviewed regularly and be updated as scientific and medical literature becomes available. For more information on how Medical Policy Bulletins are developed, go to the About This Site section of this Medical Policy Web site.



Policy

Coverage is subject to the terms, conditions, and limitations of the member's contract.

MEDICALLY NECESSARY

Asparaginase Erwinia chrysanthemi (Erwinaze®) is considered medically necessary and, therefore, covered when all of the following are met:
  • Asparaginase Erwinia chrysanthemi (Erwinaze®) is being used as a component of a multi-agent chemotherapeutic regimen.
  • Individual is diagnosed with acute lymphoblastic leukemia (ALL).
  • Individual has history of documented hypersensitivity (i.e., systemic allergic reaction or anaphylaxis) to Escherichia coli-derived asparaginase (e.g., pegaspargase [Oncaspar®], asparaginase [Elspar®]).
  • Individual does not have any of the following contraindications:
    • History of serious hypersensitivity reactions (National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] Grades 3 and 4) to asparaginase Erwinia chrysanthemi (Erwinaze®), including anaphylaxis
    • History of serious pancreatitis with prior L-asparaginase therapy manifested by abdominal pain for longer than 72 hours and amylase elevation greater than or equal to 2.0 times the upper limit of normal (ULN)
    • History of serious thrombosis (e.g., sagittal sinus thrombosis or pulmonary embolism) with prior L-asparaginase therapy
    • History of serious hemorrhagic events (NCI CTCAE Grade 4 with CNS involvement) with prior L-asparaginase therapy

EXPERIMENTAL/INVESTIGATIONAL

All other uses for asparaginase Erwinia chrysanthemi (Erwinaze®) are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the Company medical policy on off-label coverage for prescription drugs and biologics.

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the drug.
Guidelines

NATIONAL CANCER INSTITUTE COMMON TERMINOLOGY CRITERIA FOR ADVERSE EVENTS

National Cancer Institute Common Terminology Criteria for Adverse Events describes the severity of adverse events (i.e., organ toxicity) for individuals receiving chemotherapy. Adverse events are evaluated on a Grade Scale of 1-5 with unique clinical descriptions of severity for each adverse event. The general guideline is:
  • Grade 1: asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated
  • Grade 2: minimal, local, or noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily living (ADL)
  • Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling, limiting self ADL
  • Grade 4: life-threatening consequences, urgent intervention indicated Grade 5: death related to adverse event

For additional information about organ-specific clinical descriptions refer to https://ctep.cancer.gov/protocoldevelopment/electronic_applications/ctc.htm.

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, asparaginase Erwinia chrysanthemi (Erwinaze®) is covered under the medical benefits of the Company’s products when the medical necessity criteria listed in this medical policy are met.

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

Asparaginase Erwinia chrysanthemi (Erwinaze®) was approved by the FDA on November 2011 for the treatment of individuals with acute lymphoblastic leukemia (ALL) who have developed hypersensitivity to E. coli--derived asparaginase.

Description

According to the American Cancer Society, there are approximately 6,590 new cases of acute lymphoblastic leukemia (ALL) (occurring in children and adults) in the United States. Children younger than 5 years of age have the highest level of risk for developing ALL. ALL, also known as acute lymphocytic leukemia, is a cancer that starts in the white blood cell precursors in the bone marrow and progresses rapidly to spread to other parts of the body.

Treatment for ALL is typically divided into several phases: induction, consolidation, and maintenance. Induction therapy is the initial phase of treatment with the objective of achieving complete remission. Consolidation, or the intensification phase, is a shorter period of chemotherapy to further reduce the amount of leukemic cells and to prevent the development of drug resistance. The individual's level of risk will determine the intensity of the chemotherapy regimen. The maintenance phase helps to prolong the duration of remission.

Asparaginase is commonly used for the treatment of ALL. Leukemic cells lack asparagine synthetase activity, making them unable to synthesize asparagine. They have to depend on an exogenous source of amino acid asparagine for protein metabolism and survival, which is typically part of the regimen for induction therapy. Clinical studies have demonstrated that asparaginase can be used to achieve complete remission for individuals during their first relapse.

In November 2011, asparaginase Erwinia chrysanthemi(Erwinaze®) was approved by the US Food and Drug Administration (FDA) as a component of the multi-agent chemotherapeutic regimen for the treatment of individuals with ALL who have developed a hypersensitivity to Escherichia coli(E. coli) derived asparaginase. Erwinia chrysanthemi(Erwinaze®) catalyzes the deamidation of asparagine to aspartic acid and ammonia, leading to a reduction of circulating asparagine.

The safety and efficacy of asparaginase Erwinia chrysanthemi (Erwinaze®), for intramuscular injection, was established in a single-arm multi-center open-label trial. Enrolled in the trial were 58 individuals who were unable to continue to receive pegaspargase due to hypersensitivity reactions. The main outcome measure was the proportion of individuals who achieved a serum trough asparaginase level of greater than or equal to 0.1 IU/mL. A serum trough asparaginase level of greater than or equal to 0.1 IU/mL has been demonstrated to correlate with asparagine depletion and to serum levels that predict clinical efficacy. Individuals received asparaginase Erwinia chrysanthemi (Erwinaze®) 25,000 IU/m2 intramuscularly for two weeks (total six doses). Greater than 50 percent of the individuals achieved the pre-specified trough asparaginase level at 48 or 72 hours following the third dose.

The safety and efficacy of asparaginase Erwinia chrysanthemi (Erwinaze®), for intravenous infusion, was studied in an open-label, single-arm, multicenter, pharmacokinetic study. This study enrolled 30 individuals being treated for ALL or lymphoblastic lymphoma, following an allergy to E. coli asparaginase or pegaspargase. Individuals received asparaginase Erwinia chrysanthemi (Erwinaze®) 25,000 IU/m2/dose, intravenously, three days per week for up to 30 weeks. The primary endpoint was determined by the proportion of individuals with a two-day pre-dose serum asparaginase activity level (48-hour levels taken after the fifth dose) greater than or equal to 0.1 IU/mL in the first two weeks of asparaginase Erwinia chrysanthemi (Erwinaze®) treatment. The primary endpoint was observed in 83 percent of individuals.

There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company’s off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.
References


American Hospital Formulary Service (AHFS). Drug Information 2018. Asparaginase. [Lexicomp Online Web site]. 08/02/2016. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed October 2, 2018.

Asparaginase (Erwinia chrysanthemi). American Hospital Formulary Services (AHFS) Drug Information 2018. [ Lexi-Comp website]. 2/27/2018. Available at: http://online.lexi.com/lco/action/doc/retrieve/docid/complete_ashp/4092240 [via subscription only]. Accessed September 13, 2018.

Asparaginase Erwinia chrysanthemi (Erwinaze®). Jazz Pharmaceuticals, Inc. March 2016. Available at:http://www.erwinaze.com/. Accessed September 13, 2018.

Asparaginase. Micromedex® Healthcare Series. DrugDex®. [Micromedex Web site]. Last modified 11/11/2016. Available at: http://www.micromedexsolutions.com/[via subscription only]. Accessed September 13, 2018.

Einsiedel H, Stackelberg A, Hartmann R, et. al. Long term outcome in children with relapsed ALL by risk-stratified salvage therapy: results of trial acute lymphoblastic leukemia-relapse study of the Berlin-Frankfurt-Munster Group 87. J Clin Oncol. 2005;23(31):7942-7950.

Elsevier’s Clinical Pharmacology Compendium. Asparaginase (Erwinia chrysanthemi). [ClinicalKey Web site]. 03/12/2018. Available at: https://www.clinicalkey.com/. [via subscription only]. Accessed September 13, 2018.

Keating G. Asparaginase Erwinia chrysanthemi (Erwinase®): A guide to its use in acute lymphoblastic leukemia in the USA. BioDrugs. 2013;27:413-418.

Lexi-Drugs Compendium. Asparaginase (Erwinia). [Lexicomp Online Web site]. 08/21/2018. Available at: http://online.lexi.com/lco/action/doc/retrieve/docid/patch_f/3566871 [via subscription only]. Accessed September 13, 2018.

National Comprehensive Cancer Network (NCCN). NCCN Guidelines Clinical Practice Guidelines in Oncology: Acute Lymphoblastic Leukemia V1.2018. [NCCN Web site] subscription required. 03/12/2018. Available at: https://www.nccn.org/professionals/physician_gls/pdf/all.pdf. Accessed September 13, 2018.

National Comprehensive Cancer Network (NCCN). NCCN Drug and Biologics Compendium. Asparaginase Erwinia chrysnathemi. [National Comprehensive Cancer Network Web site]. V1.2018. 03/12/2018. Subscription required. Available at: https://www.nccn.org/professionals/drug_compendium/MatrixGenerator/Matrix.aspx?AID=396. Accessed September 13, 2018.

Salzer W, Asselin B, SUpko, et. al. Erwinina asparaginase achieves therapeutic activity after pegaspargase allergy: a report from the Children's Oncology Group. Blood. 2013;122(4):507-514

Seiter K. Acute lymphoblastic leukemia treatment & management. [ Medscape Website]. 07/17/2018. Available at: http://emedicine.medscape.com/article/207631-treatment. Accessed September 13, 2018.

US Department of Health and Human Services. Common terminology criteria for adverse events (CTCTAE). V5.0. 11/27/2017. Available at: https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_8.5x11.pdf. Accessed September 13, 2018.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Approval letter. Asparaginase Erwinia chrysanthemi (Erwinaze®). [FDA Web site]. 11/18/2011. Available at:
http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2011/125359s000ltr.pdf. Accessed September 13, 2018.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Prescribing information. Asparaginase Erwinia chrysanthemi (Erwinaze®). [FDA Web site]. 03/29/2016. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=BasicSearch.process. Accessed September 13, 2018.





Coding

Inclusion of a code in this table does not imply reimbursement. Eligibility, benefits, limitations, exclusions, precertification/referral requirements, provider contracts, and Company policies apply.

The codes listed below are updated on a regular basis, in accordance with nationally accepted coding guidelines. Therefore, this policy applies to any and all future applicable coding changes, revisions, or updates.

In order to ensure optimal reimbursement, all health care services, devices, and pharmaceuticals should be reported using the billing codes and modifiers that most accurately represent the services rendered, unless otherwise directed by the Company.

The Coding Table lists any CPT, ICD-9, ICD-10, and HCPCS billing codes related only to the specific policy in which they appear.

CPT Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD - 10 Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD -10 Diagnosis Code Number(s)

C91.00 Acute lymphoblastic leukemia not having achieved remission

C91.01 Acute lymphoblastic leukemia, in remission

C91.02 Acute lymphoblastic leukemia, in relapse



HCPCS Level II Code Number(s)

J9019 Injection, asparaginase (Erwinaze), 1,000 IU


Revenue Code Number(s)

N/A

Coding and Billing Requirements


Cross References


Policy History

Revisions for 08.01.35a
11/19/2018.This version of the policy will become effective 11/19/2018.

The policy has been updated to communicate changes based on National Comprehensive Cancer Network (NCCN). Criteria have been revised to include hypersensitivity to Oncaspar.

08.01.35
04/11/2018This policy has been reissued in accordance with the Company's annual Policy Confirmation Review track. The references were updated accordingly. The policy was updated to be consistent with current template wording and format. The adoptable source for this policy is FDA labeling (03/2016), Micromedex (11/2016), and AHFS (02/2018), NCCN compendium (03/2018), NCCN Acute Lymphoblastic Leukemia Guidelines V1.2018 (03/2018).


Effective 10/05/2017 this policy has been updated to the new policy template format.


Version Effective Date: 11/19/2018
Version Issued Date: 11/19/2018
Version Reissued Date: N/A

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