Archived Policies - Prescription Drugs


Alemtuzumab (Lemtrada)

Number:RX501.077

Effective Date:09-01-2015

End Date:09-14-2016

Coverage:

Medical policies are a set of written guidelines that support current standards of practice. They are based on current peer-reviewed scientific literature. A requested therapy must be proven effective for the relevant diagnosis or procedure. For drug therapy, the proposed dose, frequency and duration of therapy must be consistent with recommendations in at least one authoritative source. This medical policy is supported by FDA-approved labeling and nationally recognized authoritative references. These references include, but are not limited to:  MCG care guidelines, Hayes, DrugDex (IIb level of evidence or higher), NCCN Guidelines (IIb level of evidence or higher), NCCN Compendia (IIb level of evidence or higher), professional society guidelines, and CMS coverage policy.

Alemtuzumab (Lemtrada) may be considered medically necessary for patients 17 years of age or older for the treatment of relapsing forms of multiple sclerosis (MS) (relapsing-remitting or secondary progressive multiple sclerosis) when the patient meets ALL the following criteria:

Inadequate response to at least two drugs indicated for the treatment of MS,

HIV negative,

Not used in combination with another MS disease modifying agent, and

The prescriber and patient are enrolled in the Lemtrada Risk Evaluation and Mitigation Strategy (REMS) program.

Alemtuzumab (Lemtrada) is considered experimental, investigational and/or unproven for all other indications.

NOTE: The recommended dosage of Lemtrada is 12 mg/day administered by intravenous infusion for 2 treatment courses:

First Treatment Course: 12 mg/day on 5 consecutive days (60 mg total dose)

Second Treatment Course: 12 mg/day on 3 consecutive days (36 mg total dose) administered 12 months after the first treatment course.

Description:

Background

Alemtuzumab (Lemtrada) is a multiple sclerosis (MS) disease-modifying agent. Lemtrada can potentially alter the course of disease by lessening the frequency of clinical exacerbations. Lemtrada is a monoclonal antibody that targets CD52, a protein abundant on T and B cells. Circulating T and B cells are thought to be responsible for the damaging inflammatory process in MS. Lemtrada depletes circulating T and B lymphocytes after each treatment course. Lymphocyte counts then increase over time (1).

Regulatory Status (2)

The U. S. Food and Drug Administration (FDA) approved Lemtrada on November 14, 2014. Lemtrada is a CD52-directed cytolytic monoclonal antibody indicated for the treatment of patients with relapsing forms of MS. Because of its safety profile, the use of Lemtrada should be reserved for patients who had an inadequate response to two or more drugs indicated for the treatment of MS.

The Lemtrada label includes a boxed warning citing the risk of autoimmune conditions such as immune thrombocytopenia and anti-glomerular basement membrane disease. Complete blood counts with differential, serum creatinine levels, and urinalysis with urine cell counts at periodic intervals for 48 months after last dose should be monitored. Lemtrada also carries boxed warnings for infusion reactions which must be administered in an appropriate setting to manage anaphylaxis or serious infusion reactions, and a boxed warning for an increased risk of malignancy, including thyroid cancer, melanoma and lymphoproliferative disorders. Baseline and yearly skin exams should be done.

Lemtrada is contraindicated for patients with Human Immunodeficiency Virus (HIV) infection. Lemtrada can cause prolonged reductions of CD4+ lymphocyte counts which can further disease progression in patients with HIV.

The Lemtrada is available only through a restricted distribution program under a REMS program. The Lemtrada Risk Evaluation and Mitigation Strategy (REMS) Program, a comprehensive risk management program with frequent monitoring, is being implemented to help mitigate the serious risks associated with the medications use.

Safety and effectiveness of the Lemtrada in patients younger than 17 years of age have not been established.

Rationale:

The efficacy of Lemtrada was demonstrated in two randomized trials that evaluated Lemtrada 12 mg in patients with relapsing-remitting multiple sclerosis (RRMS). Lemtrada was administered by intravenous infusion once daily over a 9 day course, followed one year later by intravenous infusion once daily over a 3-day course. Both studies included patients who had experienced at least 2 relapses during the 2 years prior to trial entry and at least 1 relapse during the year prior to trial entry. Neurological examinations were performed every 12 weeks and at the time of suspected relapse. Magnetic resonance imaging (MRI) evaluations were performed annually.

CARE-MS I

This was a 2-year randomized, open-label, rater-blinded, active comparator (interferon beta-1a 44 micrograms administered subcutaneously three times a week) controlled study in patients with RRMS. (4) Patients entering had Expanded Disability Status Scale (EDSS) scores of 3 or less and no prior treatment for multiple sclerosis. Patients were randomized to receive Lemtrada (n=376) or interferon beta-1a (n=187). At baseline, the mean age was 33 years, the mean disease duration was 2 years, and the mean EDSS score was 2. The clinical outcome measures were the annualized relapse rate (ARR) over 2 years and the time to confirmed disability progression. The MRI outcome measure was the change in T2 lesion volume.

After two years 78% of those on Lemtrada remained relapse-free, this was significantly more than the 59% who remained relapse-free on interferon beta-1a (Rebif). There was no significant difference between the treatment groups for the time to confirmed disability progression and for the primary MRI endpoint (change in T2 lesion volume).

CARE-MS II

This study was a 2 year randomized, open-label, rater-blinded, active comparator (interferon beta-1a 44 micrograms administered subcutaneously three times a week) controlled study in patients with RRMS. (5) Patients had an EDSS score of 5 or less and had to have experienced at least one relapse while on interferon beta or glatiramer acetate therapy.

Patients were randomized to receive Lemtrada (n=426) or interferon beta-1a (n=202). At baseline, the mean age was 35 years, the mean disease duration was 4.5 years, and the mean EDSS score was 2.7.

The clinical outcome measures were the annualized relapse rate (ARR) over 2 years and the time to confirmed disability progression. Confirmed disability progression was defined as at least a 1 point increase above baseline EDSS (1.5 point increase for patients with baseline EDSS of 0) sustained for 6 months. The MRI outcome measure was the change in T2 lesion volume.

After two years, the annual relapse rate for those on Lemtrada was 0.26 compared to 0.52 for those on Rebif, representing a 49% lower risk of relapses. In addition, on average fewer people on Lemtrada had an increase (worsening) in their EDSS score compared to those on interferon beta-1a , (13% for Lemtrada vs. 21% on interferon beta-1a – a 42% difference that was statistically significant. After two years, 65% of those on Lemtrada remained relapse-free compared to 47% on interferon beta-1a, which was also statistically significantly. Time to onset of 6-month confirmed disability progression was significantly delayed with Lemtrada treatment compared to interferon beta-1a. There was no significant difference between the treatment groups for the change in T2 lesion volume.

Summary

In both the randomized trials addressed above, the rate of MS relapse was significantly reduced with alemtuzumab (rate of relapse, 22% and 35%) compared with interferon beta-1a (rate of relapse, 40% and 53%) in untreated (CARE-MS I) and previously treated (CARE-MS II) patients with relapsing-remitting MS. Lemtrada significantly improved the sustained accumulation of disability over 6 months compared with interferon beta-1a among previously treated patients (12.71% vs 21.13%); however, significance was not reached among previously untreated patients. In both studies alemtuzumab was associated with a higher incidence of serious infections, immune thrombocytopenia, autoimmunity, and thyroid papillary carcinoma, as well as a significantly higher incidence of herpes viral infections despite prophylaxis with acyclovir.

Contract:

Each benefit plan, summary plan description or contract defines which services are covered, which services are excluded, and which services are subject to dollar caps or other limitations, conditions or exclusions. Members and their providers have the responsibility for consulting the member's benefit plan, summary plan description or contract to determine if there are any exclusions or other benefit limitations applicable to this service or supply. If there is a discrepancy between a Medical Policy and a member's benefit plan, summary plan description or contract, the benefit plan, summary plan description or contract will govern.

Coding:

CODING:

Disclaimer for coding information on Medical Policies

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.

The presence or absence of procedure, service, supply, device or diagnosis codes in a Medical Policy document has no relevance for determination of benefit coverage for members or reimbursement for providers. Only the written coverage position in a medical policy should be used for such determinations.

Benefit coverage determinations based on written Medical Policy coverage positions must include review of the member’s benefit contract or Summary Plan Description (SPD) for defined coverage vs. non-coverage, benefit exclusions, and benefit limitations such as dollar or duration caps.

CPT/HCPCS/ICD-9/ICD-10 Codes

The following codes may be applicable to this Medical policy and may not be all inclusive.

CPT Codes

None

HCPCS Codes

J0202, J3590, J3490, C9399, [Deleted 1/2016: Q9979]

ICD-9 Diagnosis Codes

Refer to the ICD-9-CM manual

ICD-9 Procedure Codes

Refer to the ICD-9-CM manual

ICD-10 Diagnosis Codes

Refer to the ICD-10-CM manual

ICD-10 Procedure Codes

Refer to the ICD-10-CM manual


Medicare Coverage:

The information contained in this section is for informational purposes only. HCSC makes no representation as to the accuracy of this information. It is not to be used for claims adjudication for HCSC Plans.

The Centers for Medicare and Medicaid Services (CMS) does not have a national Medicare coverage position. Coverage may be subject to local carrier discretion.

A national coverage position for Medicare may have been developed since this medical policy document was written. See Medicare's National Coverage at <http://www.cms.hhs.gov.

References:

1. Product Information: LEMTRADA(TM) intravenous injection, alemtuzumab intravenous injection. Genzyme Corporation, Cambridge, MA, 2014 www.genzyme.com. Accessed April 1, 2015.

2. Food and Drug Administration. FDA Labeling. Lemtrada ™ (alemtuzumab) injection Available at: <http://www.fda.gov> Accessed April 1, 2015.

3. TEC Specialty Pharmacy Report #03-2013. Chicago Illinois, Blue Cross Blue Shield Association Technology Evaluation Center. February 22, 2013

4. Cohen JA, Coles AJ, Arnold DL, et al. 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(9856):1819-1828.

5. Coles AJ, Twyman CL, Arnold DL, et al. Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial. Lancet 2012; 380 (9856):1829-1839.

Policy History:

Date Reason
9/1/2015 New medical document. Alemtuzumab (Lemtrada) may be considered medically necessary for patients 17 years of age or older for the treatment of relapsing forms of multiple sclerosis (MS) (relapsing-remitting or secondary progressive multiple sclerosis) when the patient meets ALL the following criteria: 1) Inadequate response to at least two drugs indicated for the treatment of MS, 2) HIV negative, 3) Not used in combination with another MS disease modifying agent, and 4) When the prescriber and patient are enrolled in the Lemtrada Risk Evaluation and Mitigation Strategy (REMS) program. In addition the following was added: Alemtuzumab (Lemtrada) is considered experimental, investigational and/or unproven for all other indications.

Archived Document(s):

Title:Effective Date:End Date:
Alemtuzumab (Lemtrada)10-15-201710-14-2018
Alemtuzumab (Lemtrada)09-15-201610-14-2017
Alemtuzumab (Lemtrada)09-01-201509-14-2016
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