Description
Alemtuzumab (Lemtrada^™) is a CD52-directed cytolytic monoclonal antibody indicated for the treatment of patients with relapsing forms of multiple sclerosis (MS). Because of its safety profile, the use of alemtuzumab (Lemtrada^™) should generally be reserved for patients who have had an inadequate response to two or more drugs indicated for the treatment of MS.

Alemtuzumab (Lemtrada^™) is a recombinant humanized IgG1 kappa monoclonal antibody directed against the cell surface glycoprotein, CD52. The precise mechanism by which alemtuzumab exerts its therapeutic effects in multiple sclerosis is unknown, but is presumed to involve binding to CD52, a cell surface antigen present on T and B lymphocytes, and on natural killer cells, monocytes and macrophages. Following cell surface binding to T and B lymphocytes, alemtuzumab results in antibody-dependent cellular cytolysis and complement-mediated lysis. Based on animal data, Alemtuzumab (Lemtrada^™) may cause fetal harm.

Policy  
Alemtuzumab (Lemtrada) will be considered MEDICALLY NECESSARY if the following conditions are met:

1. Patient has a diagnosis of a relapsing form of multiple sclerosis (Relapsing-remitting MS (RRMS), Progressive-relapsing MS (PRMS), Secondary progressive MS (SPMS) with documented relapses) 
2. Patient has had an inadequate response to 2 or more drugs indicated for the treatment of multiple sclerosis
   • Avonex (interferon beta-1a)
   • Copaxone (glatiramer acetate)/Glatiramer
   • Glatopa (glatiramer acetate)
   • Extavia (interferon beta-1b)
   • Gilenya (fingolimod)
   • Tecfidera (dimethyl fumarate)
   • Aubagio (teriflunomide)
   • Betaseron (interferon beta-1b)
   • Plegridy (peginterferon beta-1a)
   • Rebif (interferon beta-1a)
   • Tysabri (natalizumab)
3. Submission of medical records (e.g., chart notes) documenting the planned dates of Lemtrada infusions
   • Patient completed the first course of treatment greater than or equal to 12 months prior to the planned infusion of the second course (submit documentation of the planned dates of infusions)
   • The request is NOT for a third (or subsequent) course of therapy with Lemtrada.

Alemtuzumab (Lemtrada) is contraindicated in patients with HIV.

Alemtuzumab (Lemtrada) is investigational and/or unproven therefore is considered NOT MEDICALLY NECESSARY for all uses that do not meet the above criteria.

Policy Guidelines
Alemtuzumab (Lemtrada^™) is administered by intravenous infusion.

For the treatment of relapsing multiple sclerosis, the first treatment course of 12 mg/day administered on 5 consecutive days is followed by the second treatment course of 12 mg/day administered on 3 consecutive days 12 months after the first treatment course.

Rationale 
This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, Blue Cross Blue Shield Association technology assessment program (TEC) and other non-affiliated technology evaluation centers, reference to federal regulations, other plan medical policies and accredited national guidelines.

The efficacy of Lemtrada was demonstrated in 2 studies (Study 1 and Study 2) that evaluated Lemtrada 12 mg in patients with relapsing remitting multiple sclerosis. Lemtrada was administered by IV infusion once daily over a 5-day course, then once daily over a 3-day course. Study 1 was a randomized, open label, active comparator study over a 2-year period in patients with relapsing remitting multiple sclerosis. The active comparator arm was interferon beta-1a 44 mcg given subcutaneously three times per week. Clinical outcomes measured were the annualized relapse rate (ARR) over 2 years and the time to confirmed disability progression. The ARR was significantly lower in the Lemtrada group as compared to the interferon group (0.26 vs. 0.52, p < 0.0001). The proportion of patients with disability progression at year 2 was also statistically lower in the Lemtrada group (13 percent vs. 21 percent), p = 0.0084). The change in T2 lesion volume from baseline was not statistically significant between the two groups. The setup of Study 2 was similar to that of Study 1. The ARR was significantly lower in the Lemtrada group (0.18 vs. 0.39, p < 0.0001). There was no significant difference between the treatment groups for the time to confirmed disability progression and for the primary MRI endpoint.

References

1. Alemtuzumab (Lemtrada™). Prescribing information. November 2014. Available at: http://products.sanofi.us/lemtrada/lemtrada.pdf
2. U.S. Food and Drug Administration (FDA). http://www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM425409.pdf

Coding Section 

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. 

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, Blue Cross Blue Shield Association technology assessment program (TEC) and other non-affiliated technology evaluation centers, reference to federal regulations, other plan medical policies and accredited national guidelines.

"Current Procedural Terminology © American Medical Association. All Rights Reserved" 

History From 2015 Forward