Notification



Notification Issue Date:



Medical Policy Bulletin


Title:Alemtuzumab (Lemtrada®)

Policy #:08.01.22c

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

Alemtuzumab (Lemtrada®) is considered medically necessary and, therefore, covered for:
  • Individuals with relapsing-remitting multiple sclerosis when the following criteria are met:
    • Inadequate clinical response to two or more drugs indicated for the treatment of multiple sclerosis as defined by relapse, and/or accumulating disability, and/or multiple new or enlarging of lesions of brain and/or spinal cord
      • Inadequate clinical response to one or more drugs, if individual is considered high risk for disability (e.g., The spinal MRI shows high burden of lesions, but the physical exam does not demonstrate the extent of disability)
    • Human immunodeficiency virus (HIV)--negative
  • Individuals with aggressive relapsing-remitting multiple sclerosis defined as, but not limited to, accumulating disability, multiple new or enlarging of lesions of brain and/or spinal cord in the first year of illness
    • Human immunodeficiency virus (HIV)--negative

NOT ELIGIBLE FOR REIMBURSEMENT

Effective September 4, 2012 Campath is no longer available commercially and, therefore not eligible for reimbursement. It may be provided through the Campath Distribution Program free of charge. Please contact the manufacturer.

EXPERIMENTAL/INVESTIGATIONAL

All other uses for alemtuzumab (Lemtrada®) 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

DOSAGE INFORMATION

According to the FDA-approved label, the recommended dosage of alemtuzumab (Lemtrada®) is 12 mg/day by intravenous infusion for two treatment courses. The first course is for 5 consecutive days. The second course is 12 months after the first treatment course for 3 consecutive days at 12 mg/day. Individuals should be given high-dose corticosteroids (1000 mg methylprednisolone or equivalent) immediately prior to infusion and for the first 3 days of each treatment course. Following the second course, subsequent treatment courses of 12 mg/day on 3 consecutive days may be administered, as needed, at least 12 months after the last dose of any prior treatment courses.

PEDIATRIC USE

The safety and effectiveness of alemtuzumab (Lemtrada®) in pediatric patients below the age of 17 years have not been established. Alemtuzumab (Lemtrada®) is not indicated for use in pediatric patients due to the risk of severe adverse events.

BLACK BOX WARNINGS

Refer to the specific manufacturer's prescribing information for any applicable Black Box Warnings.

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, alemtuzumab (Lemtrada®) 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

Alemtuzumab (Lemtrada®) was approved by the FDA in November 2014 for the treatment of individuals with relapsing forms of multiple sclerosis.

Description

Alemtuzumab (Lemtrada®) is a recombinant humanized monoclonal antibody directed against a cell surface glycoprotein found on T-lymphocytes and B-lymphocytes resulting in antibody-dependent cellular cytolysis and complement-mediated lysis. Alemtuzumab (Lemtrada®) was originally approved as alemtuzumab (Campath®) in May 2001. In 2012 Genzyme pulled alemtuzumab (Campath®) from the market. In November 2014, alemtuzumab was approved as (Lemtrada®) for the treatment of individuals with relapsing forms of multiple sclerosis. In light of its safety profile, the US Food and Drug Administration (FDA) approved alemtuzumab (Lemtrada®) for individuals who have had an inadequate response to two or more drugs indicated for the treatment of multiple sclerosis.

Multiple sclerosis is caused by an immune-mediated process in which the body's immune system has an abnormal response directed against the central nervous system causing demyelination with loss of oligodendrocytes and astroglial scarring.

PEER REVIEWED LITERATURE

The safety and efficacy of Alemtuzumab (Lemtrada®) was evaluated in 2 randomized, controlled, phase 3 trials on individuals with relapsing-remitting multiple sclerosis who had experienced at least 2 relapses during the prior 2 years and at least 1 relapse during the prior year.

The Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis (CARE-MS-1) trial was a 2-year randomized, open-label, rater-blinded study assessing the safety and efficacy of alemtuzumab (Lemtrada®) as first-line treatment for relapsing-remitting multiple sclerosis. Individuals with an expanded disability status scale (EDSS) score of 3 or lower, cranial abnormalities on MRI due to multiple sclerosis, and no previous multiple sclerosis treatment, except corticosteroids, were randomized to receive alemtuzumab (Lemtrada®) (N=376) or interferon beta 1a(N=187). The clinical outcome measures were annualized relapse rate (ARR) over 2 years and time to 6-month sustained accumulation of disability. Alemtuzumab (Lemtrada®) ARR was 0.18 compared to interferon beta 1a of 0.39, a 55% relative reduction in risk. At year 2, 78% individuals on alemtuzumab (Lemtrada®) were relapse-free compared to 59% of the interferon beta 1a group. There was not a significant difference between the two groups for time to 6-month sustained accumulation of disability. The most frequently reported adverse event for alemtuzumab was infusion-associated reactions (90% of 376 individuals), with 3% having serious adverse events. The most frequently reported adverse event for interferon beta 1a was infection (45% of 187), with 1% having a serious infection.

In the Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis (CARE-MS-2) trial, alemtuzumab (Lemtrada®) was compared to interferon beta 1a to assess safety and efficacy in individuals with relapsing-remitting multiple sclerosis who have relapsed despite first-line therapy of interferon beta or glatiramer acetate for 6 months. In this 2-year randomized, open-label, rater-blinded study, individuals with EDSS of 5 or lower and cranial and spinal MRI lesions were randomized to receive alemtuzumab (Lemtrada®) (N=426) or interferon beta 1a(N=202). The clinical outcome measures were the same as the first study of ARR over 2 years and time to 6-month sustained accumulation of disability. There was a significant reduction in ARR when the alemtuzumab (Lemtrada®) group (0.26) was compared to interferon beta 1a (0.52) of 49%. Alemtuzumab (Lemtrada®) significantly reduced the risk of sustained accumulation of disability by 42% compared to interferon beta 1a. At year 2, 65.4% of the alemtuzumab (Lemtrada®) group were relapse free as opposed to the interferon beta 1a group in which 46.7% were relapse free. The most frequently reported adverse event for alemtuzumab was infusion-associated reactions (90% of 435 individuals), with 3% having serious adverse events. The most frequently reported adverse event for interferon beta 1a was infection (66% of 187), with 1% having a serious infection.

RISK EVALUATION AND MITIGATION STRATEGY (REMS)

Alemtuzumab (Lemtrada®) drug was approved by the US Food and Drug Administration (FDA) with a risk evaluation and mitigation strategy (REMS). The goal was to ensure that the benefits of the drug outweigh the risks of autoimmune conditions, infusion reactions, and malignancies through a restricted distribution program.

OFF-LABEL INDICATIONS

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


Alemtuzumab (Lemtrada®) [prescribing information]. Cambridge, MA: Genzyme Corporation; 01/2019. Available at: http://products.sanofi.us/lemtrada/lemtrada.pdf. Accessed March 12, 2019.

American Hospital Formulary Service (AHFS). Drug Information 2019. Lemtrada. [Lexicomp Online Web site]. 12/11/15. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed March 12, 2019.

CAMMS223 Trial Investigators. Alemtuzumab vs. interferon beta-1a in early multiple sclerosis. New Engl J Med. 2008;359:1786-801.

Cohen J, Coles A. Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial. Lancet. 2012; 380:1819-28.

Coles A, Twyman C. Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial. Lancet. 2012;380:1829-1839.

Elsevier's Clinical Pharmacology Compendium. Alemtuzumab. [Clinical Pharmacology Web site. 01/24/19. Available at: https://www.clinicalkey.com/pharmacology/ [via subscription only]. Accessed March 12, 2019.

Lexi-Drugs Compendium. Alemtuzumab. [Lexicomp Online Web site]. 03/02/19. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed March 12, 2019.

National Institute for Health and Care Excellence (NICE). Technology Appraisal Guidance 312: Alemtuzumab for treating relapsing-remitting multiple sclerosis. [NICE Web site]. May 2014. Available at: https://www.nice.org.uk/guidance/ta312 . Accessed March 12, 2019.

Polman C, Reingold S. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonlad criteria. Ann Neurol. 2011;69:292-301.

Truven Health Analytics. Micromedex® DrugDex® Compendium. Lemtrada. 02/20/19. Greenwood Village, CO. [Micromedex® Solutions Web site]. Available at:
http://www.micromedexsolutions.com/micromedex2/librarian. Accessed March 12, 2019.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Alemtuzumab (Lemtrada®). Supplemental Approval for REMS. [FDA Web site]. Last Update: 11/28/18. Available at: https://www.accessdata.fda.gov/scripts/cder/rems/index.cfm?event=IndvRemsDetails.page&REMS=340 . Accessed March 12, 2019.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Drugs@FDA. Alemtuzumab (Lemtrada®) prescribing information. [FDA Web site]. 01/16/19. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/ . Accessed March 12, 2019.





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)

G35 Multiple sclerosis


HCPCS Level II Code Number(s)

J0202 Injection, alemtuzumab, 1 mg


Revenue Code Number(s)

N/A

Coding and Billing Requirements


Cross References


Policy History

08.01.22c
04/10/2019The policy has been reviewed and reissued to communicate the Company’s continuing position on alemtuzumab (Lemtrada®).
06/06/2018This policy has been reissued in accordance with the Company's annual review process.
10/18/2017This policy was updated to expand coverage to individuals deemed high risk for disability.


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


Version Effective Date: 10/18/2017
Version Issued Date: 10/18/2017
Version Reissued Date: 04/10/2019

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