BlueCross BlueShield of Tennessee Medical Policy Manual

Lecanemab-irmb (Leqembi™)

IMPORTANT REMINDER

We develop Medical Policies to provide guidance to Members and Providers.  This Medical Policy relates only to the services or supplies described in it.  The existence of a Medical Policy is not an authorization, certification, explanation of benefits or a contract for the service (or supply) that is referenced in the Medical Policy.  For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed.  If there is a conflict between the medical policy and a health plan or government program (e.g., TennCare), the express terms of the health plan or government program will govern.

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.

FDA-Approved Indication

Leqembi is indicated for the treatment of Alzheimer’s disease. Treatment with Leqembi should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was initiated in clinical trials.

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.    Initial Requests:

1.     Genetic testing results documenting a mutation in amyloid precursor protein (APP), presenilin-1 (PSEN1), or presenilin-2 (PSEN2), if applicable.

2.     Clinical documentation to support early onset Alzheimer’s Disease, if applicable.

3.     Medical records (e.g., chart notes) documenting the following:

i.      Diagnosis of mild cognitive impairment due to Alzheimer’s Disease or mild Alzheimer’s Disease.

ii.     Baseline assessments for any of the following assessment tools:

a.     Clinical Dementia Rating-Global Score (CDR-GS)

b.     Mini-Mental Status Examination (MMSE)

c.     Montreal Cognitive Assessment (MoCA)

4.     Presence of amyloid pathology documented by either of the following:

i.      Baseline positron emission tomography (PET) scan

ii.     Lumbar puncture results

5.     Recent (within one year) brain magnetic resonance imaging (MRI) prior to initiating treatment.

B.    Continuation requests (where applicable):

1.     Medical records (e.g., chart notes) documenting the most recent (less than 1 month prior to continuation request) assessment tool for any of the following:

i.      Clinical Dementia Rating-Global Score (CDR-GS)

ii.     Mini-Mental Status Exam (MMSE)

iii.    Montreal Cognitive Assessment (MoCA)

2.     Brain magnetic resonance imaging (MRI) results prior to the 5^th dose, 7^th dose, and 14^th dose.

       III.    EXCLUSIONS

Coverage will not be provided for members with any of the following conditions:

A.    Suspected neurodegenerative etiology of cognitive impairment other than Alzheimer’s disease (AD), including but not limited to frontotemporal lobar degeneration (FTLD) or Lewy body disease (i.e., meeting consensus criteria for possible or probable dementia with Lewy bodies).

B.    History of transient ischemic attacks (TIA), stroke, or seizures within the past 12 months.

C.    Bleeding disorder that is not under adequate control (including a platelet count <50,000 or international normalized ratio [INR] >1.5).

D.    Leqembi will not be used in combination with any other amyloid beta-directed antibodies (e.g., aducanumab).

       IV.    PRESCRIBER SPECIALTIES

This medication must be prescribed by or in consultation with a geriatrician, neurologist, psychiatrist, or neuropsychiatrist.

        V.    CRITERIA FOR INITIAL APPROVAL

Alzheimer’s Disease

  Authorization of 6 months may be granted for treatment of Alzheimer’s Disease (AD) when all of the following criteria are met:

A.    Member must meet one of the following criteria:

1.     Member is 50 years of age or older

2.     If less than 50 years of age, member has a genetic mutation in amyloid precursor protein (APP), presenilin-1 (PSEN1), or presenilin-2 (PSEN2), or other clinical documentation to support early onset AD.

B.    Member must have mild cognitive impairment due to AD or mild AD dementia.

C.    Member must have objective evidence of cognitive impairment at baseline (Appendix A)

D.    Member must have one of the following scores at baseline on any of the following assessment tools:

1.     Clinical Dementia Rating-Global Score (CDR-GS) of 0.5 or 1 (Appendix B).

2.     Mini-Mental Status Examination (MMSE) score of 21 – 30 (Appendix C).

3.     Montreal Cognitive Assessment (MoCA) score of greater than or equal to 16 (Appendix D).

E.    Member must meet one of the following criteria:

1.     Have a positron emission tomography (PET) scan confirming the presence of amyloid pathology.

2.     Have results from a lumbar puncture confirming at least one of the following detected in cerebrospinal fluid (CSF) as determined by the lab assay:

                                      i.        Presence of elevated phosphorylated tau (P-tau) protein and/or elevated total tau (T-tau) protein, and reduced beta amyloid-42 (AB42)

                                     ii.        Low AB42/AB40 ratio as determined by the lab assay detected in cerebrospinal fluid (CSF).

                                    iii.        Elevated P-Tau/AB42 ratio

                                    iv.        Elevated T-Tau/AB42 ratio

F.    Member must have a recent brain magnetic resonance imaging (MRI) within one year prior to initiating treatment to evaluate for pre-existing Amyloid Related Imaging Abnormalities (ARIA).

G.    Member meets one of the following regarding apolipoprotein E ε4 (ApoE ε4) status:

1.     Genotype testing for ApoE ε4 status has been performed prior to initiation of treatment to inform member of the risk of developing ARIA.

2.     Genotype testing has not been performed and the prescriber has informed the member that it cannot be determined if they are ApoE ε4 homozygous and may be at higher risk for ARIA.

H.    If there is concurrent use of antithrombotic medications (aspirin, other antiplatelets, or anticoagulants), the member has been on a stable dose for at least 4 weeks prior to initiation of the requested medication.

I.      Member and/or provider must currently be participating in a provider-enrolled patient registry that collects information on treatments for Alzheimer’s disease (e.g., Alzheimer’s Network for Treatment and Diagnostics (ALZ-NET)).

       VI.    CONTINUATION OF THERAPY  

Authorization of 12 months (first reauthorization after the initial 6-month approval period) may be granted for members requesting continuation of therapy when all of the following criteria are met:

A.    Member has met all initial authorization criteria at the time of initial approval.

B.    Member has been evaluated for evidence of amyloid-related imaging abnormalities (ARIA) on MRI prior to the 5^th dose, 7^th dose, and 14^th dose (Appendix E).

1.     For members with radiographic evidence of ARIA-E:

i.      Dosing may continue based on clinical judgement, if applicable, for members that meet the following criteria:

a.     Member has mild ARIA-E on MRI and is asymptomatic or has mild clinical symptoms

ii.     Dosing should be suspended until MRI demonstrates radiographic resolution and symptoms resolve for members that meet any of the following criteria:

a.     Member has mild ARIA-E on MRI and has moderate or severe clinical symptoms

b.     Member has moderate ARIA-E on MRI and is asymptomatic or has mild, moderate, or severe clinical symptoms

c.     Member has severe ARIA-E on MRI and is asymptomatic or has mild, moderate, or severe clinical symptoms

2.     For members with radiographic evidence of ARIA-H:

i.      Dosing may continue for members that meet the following criteria:

a.     Member has mild ARIA-H on MRI and is asymptomatic

ii.     Dosing should be suspended until MRI demonstrates radiographic stabilization and symptoms resolve for members that meet any of the following criteria:

a.     Member has mild ARIA-H on MRI and is symptomatic

b.     Member has moderate ARIA-H on MRI and is asymptomatic or symptomatic

c.     Member has severe ARIA-H on MRI and is asymptomatic or symptomatic

C.    Member and/or provider continues to participate in a provider-enrolled patient registry that collects information on treatments for Alzheimer’s disease (e.g., Alzheimer’s Network for Treatment and Diagnostics (ALZ-NET).

Authorization of 12 months (reauthorizations beyond initial 18 months of therapy) may be granted for members requesting continuation of therapy when all of the following criteria are met:

A.    Member has met all initial authorization criteria at the time of initial approval.

B.    Member has a positive clinical response as evidenced by stabilization or slowing of disease progression as documented by any of the following (Note: repeat assessment tool(s) must be the same tool that was submitted upon initial request): i.      CDR-Global Score (i.e., score of 0.5 or 1

        ii.     MMSE (i.e., decline of 3 points or less per year)

      iii.    MoCA (i.e., score of greater than or equal to 16)

Note: Continuation requests for members with assessment scores outside of the provided ranges (i.e. mild dementia) or who have progressed greater than the provided rate of decline may be reviewed on a case-by-case basis.

C.    Member and/or provider continues to participate in a provider-enrolled patient registry that collects information on treatments for Alzheimer’s disease (e.g., Alzheimer’s Network for Treatment and Diagnostics (ALZ-NET)).

      VII.    APPENDICES

Appendix A: Summary of clinical and cognitive evaluation for MCI due to AD

·         Cognitive concern reflecting a change in cognition reported by patient or informant or clinician (i.e. historical or observed evidence of decline over time)

·         Objective evidence of impairment in one or more cognitive domains, typically including memory (i.e., formal or bedside testing to establish level of cognitive function in multiple domains)

·         Preservation of independence in functional abilities

·         Not demented

Appendix B: Clinical Dementia Rating (CDR) Scale

The CDR is obtained through semi-structured interviews of patients and informants with cognitive functioning rated on a 5-point scale in the following domains: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. The score relates to the member’s level of dementia:

·         0 = Normal

·         0.5 = Very Mild Dementia

·         1 = Mild Dementia

·         2 = Moderate Dementia

·         3 = Severe Dementia

Appendix C: Mini-Mental Status Exam (MMSE)

The MMSE is scored on a 30-point scale, with items that assess orientation (temporal and spatial; 10 points), memory (registration and recall; 6 points), attention/concentration (5 points), language (verbal and written, 8 points), and visuospatial function (1 point). The score relates to the member’s level of dementia:

·         25 - 30 suggests normal cognition

·         20 – 24 suggests mild dementia

·         13 – 20 suggests moderate dementia

·         Less than 12 suggests severe dementia

Appendix D: Montreal Cognitive Assessment (MoCA)

Per MoCA assessment, average scores for the following ranges are:

·         Mild Cognitive Impairment: 19 – 25

·         Mild Dementia: 11 – 21

·         Normal: 26 and above

Appendix E: ARIA MRI Classification Criteria

APPLICABLE TENNESSEE STATE MANDATE REQUIREMENTS

BlueCross BlueShield of Tennessee’s Medical Policy complies with Tennessee Code Annotated Section 56-7-2352 regarding coverage of off-label indications of Food and Drug Administration (FDA) approved drugs when the off-label use is recognized in one of the statutorily recognized standard reference compendia or in the published peer-reviewed medical literature.

ADDITIONAL INFORMATION  

For appropriate chemotherapy regimens, dosage information, contraindications, precautions, warnings, and monitoring information, please refer to one of the standard reference compendia (e.g., the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) published by the National Comprehensive Cancer Network®, Drugdex Evaluations of Micromedex Solutions at Truven Health, or The American Hospital Formulary Service Drug Information).

REFERENCES

1.     Leqembi [package insert]. Nutley, NJ: Eisai Inc.; July 2023.

2.     Fagan AM, Mintun MA, Mach RH, et al. Inverse relation between in vivo amyloid imaging load and cerebrospinal fluid Abeta42 in humans. Ann Neurol. 2006;59(3):512-519.

3.     O’Bryant SE, Waring SC, Cullum CM, et al. Staging dementia using Clinical Dementia Rating Scale Sum of Boxes scores: a Texas Alzheimer's research consortium study. Arch Neurol. 2008;65(8):1091-1095. doi:10.1001/archneur.65.8.1091.

4.     CDR Dementia Staging Instrument. Knight Alzheimer Disease Research Center. https://knightadrc.wustl.edu/cdr/cdr.htm. Accessed: May 4, 2023.

5.     Morris JC. The Clinical Dementia Rating (CDR): current version and scoring rules. Neurology. 1993 Nov;43(11):2412-4.

6.     Folstein MF, Folstein SE, McHugh PR. "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975 Nov;12(3):189-98.

7.     MoCA Cognitive Assessment. https://www.mocatest.org/. Accessed: May 4, 2023.

8.     Nasreddine ZS, Phillips NA, Bédirian V, et al. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment [published correction appears in J Am Geriatr Soc. 2019 Sep;67(9):1991]. J Am Geriatr Soc. 2005;53(4):695-699.

9.     Schindler SE, Gray JD, Gordon BA, et al. Cerebrospinal fluid biomarkers measured by Elecsys assays compared to amyloid imaging. Alzheimers Dement. 2018;14(11):1460-1469.

10.  Cummings J, Aisen P, Apostolova LG, Atri A, Salloway S, Weiner M. Aducanumab: Appropriate Use Recommendations. J Prev Alzheimers Dis. 2021;8(4):398-410.

11.  Patrick RE, Hobbs K, Mathias L, Harper DG, Forester BP. The Limitations of Using Cognitive Cutoff Scores for Enrollment in Alzheimer Trials. Am J Geriatr Psychiatry. 2019;27(10):1153-1158.

12.  National Coverage Determination (NCD) for Monoclonal Antibodies Directed Against Amyloid for the Treatment of Alzheimer’s Disease (AD) (200.3 – Version 1). https://www.cms.gov/medicare-coverage-database/view/ncd.aspx?ncdid=375&ncdver=1 Accessed May 4, 2023.

13.  Trzepacz PT, Hochstetler H, Wang S, Walker B, Saykin AJ; Alzheimer’s Disease Neuroimaging Initiative. Relationship between the Montreal Cognitive Assessment and Mini-mental State Examination for assessment of mild cognitive impairment in older adults. BMC Geriatr. 2015 Sep 7;15:107.

14.  Albert MS, DeKosky ST, Dickson D, et al. The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011;7(3):270-279.

15.  Clark CM, Sheppard L, Fillenbaum GG, Galasko D, et al. Variability I annual Mini-Mental State Examination score in patients with probable Alzheimer disease: a clinical perspective of data from the Consortium to Establish a registry for Alzheimer’s Disease. Arch Neurol. 1999 Jul;56(7):857-62.

16.  Han L, Cole M, Bellavance F, McCusker J, Primeau F. Tracking cognitive decline in Alzheimer’s disease using the mini-mental state examination: a meta-analysis. Int Psychogeriatr. 2000 Jun;12(2):231-47.

17.  Morris JC, Edland S, Clark C, Galasko D, et al. The consortium to establish a registry for Alzheimer’s disease (CERAD). Part IV. Rates of cognitive change in longtidunal assessment of probable Alzheimer’s disease. Neurology. 1993 Dec;43(12)2457-65.

18.  Elecsys Phospho-Tau (181P) CSF 2022-12.

ORIGINAL EFFECTIVE DATE: 5/2/2023

MOST RECENT REVIEW DATE: 4/30/2024

ID_CHS

Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.

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