Background

Ublituximab-xiiy is a recombinant chimeric monoclonal IgG1 antibody with reduced fucose content directed against CD20-expressing B-cells. The precise mechanism by which Briumvi™ exerts its therapeutic effects in multiple sclerosis is unknown but is presumed to involve binding to CD20, a cell surface antigen present on pre-B and mature B lymphocytes. Following cell surface binding to B lymphocytes, ublituximab-xiiy results in cell lysis through mechanisms including antibody-dependent cellular cytolysis and complement-dependent cytolysis.

Policy

The use of Briumvi is MEDICALLY NECESSARY when the following criteria has been met:

• Patient is at least 18 years of age; AND
• Patient has been screened for the presence of Hepatitis B virus (HBV) prior to initiating treatment AND does not have active disease (i.e., positive HBsAg and anti-HBV tests); AND
• Patient has had baseline serum immunoglobulins assessed; AND
• Patient will not receive live or live-attenuated vaccines while on therapy or within 4 weeks prior to initiation of treatment; AND
• Patient does not have an active infection; AND
• Patient must have a confirmed diagnosis of multiple sclerosis (MS) as documented by laboratory report (i.e., MRI); AND
  • Must be used as single agent therapy; AND
  • Patient has a diagnosis of a relapsing form of MS [i.e., relapsing-remitting MS (RRMS)*, active secondary progressive disease (SPMS)**, or clinically isolated syndrome (CIS)***]

Definitive diagnosis of MS with a relapsing-remitting course is based upon BOTH dissemination in time and space. Unless contraindicated, MRI should be obtained (even if criteria are met).

• Dissemination in time (Development/appearance of new CNS lesions over time)
  • ≥ 2 clinical attacks; OR
  • 1 clinical attack AND one of the following:
    • MRI indicating simultaneous presence of gadolinium-enhancing and non-enhancing lesions at any time or by a new T2-hyperintense or gadolinium-enhancing lesion on follow-up MRI compared to baseline scan
    • CSF-specific oligoclonal bands
• Dissemination in space (Development of lesions in distinct anatomical locations within the CNS; multifocal)
  • ≥ 2 lesions; OR
  • 1 lesion AND one of the following:
    • Clear-cut historical evidence of a previous attack involving a lesion in a distinct anatomical location
    • MRI indicating ≥ 1 T2-hyperintense lesions characteristic of MS in ≥ 2 of 4 areas of the CNS (periventricular, cortical or juxtacortical, infratentorial, or spinal cord)

Active secondary progressive MS (SPMS) is defined as the following:

• Expanded Disability Status Scale (EDSS) score ≥ 3.0; AND
• Disease is progressive ≥ 3 months following an initial relapsing-remitting course (i.e., EDSS score increase by 1.0 in patients with EDSS ≤5.5 or increase by 0.5 in patients with EDSS ≥ 6);

AND

• • ≥ 1 relapse within the previous 2 years; OR
  • Patient has gadolinium-enhancing activity or new and unequivocally enlarging T2 contrast enhancing lesions as evidenced by MRI.

Definitive diagnosis of CIS is based upon ALL of the following:

• A monophasic clinical episode with patient-reported symptoms and objective findings reflecting a focal or multifocal inflammatory demyelinating event in the CNS
• Neurologic symptom duration of at least 24 hours, with or without recovery
• Absence of fever or infection
• Patient is not known to have multiple sclerosis

Definitive diagnosis of MS with a primary progressive course is based upon the following:¹⁰

• 1 year of disability progression independent of clinical relapse; AND
• TWO of the following:
  • ≥ 1 T2-hyperintense lesion characteristic of MS in one or more of the following regions of the CNS (periventricular, cortical or juxtacortical, or infratentorial)
  • ≥ 2 T2-hyperintense lesions in the spinal cord
  • Presence of CSF-specific oligoclonal bands

Authorizations can be renewed based on the following criteria:

• Patient continues to meet the universal and other indication-specific relevant criteria identified in section III; AND
• Patient has not received a dose of ocrelizumab or ublituximab within the past 5 months;

AND

• Absence of unacceptable toxicity from the drug. Examples of unacceptable toxicity include: severe infusion reactions, severe infections, progressive multifocal leukoencephalopathy, hypogammaglobulinemia, etc.; AND
• Continuous monitoring of response to therapy indicates a beneficial response [manifestations of MS disease activity include, but are not limited to, an increase in annualized relapse rate (ARR), development of new/worsening T2 hyperintensities or enhancing lesions on brain/spinal MRI, and progression of sustained impairment as evidenced by expanded disability status scale (EDSS), timed 25-foot walk (T25-FW), 9-hole peg test (9-HPT)]
  • Inadequate response, in those who have been adherent and receiving therapy for sufficient time to realize the full treatment effect, is defined as ≥ 1 relapse, ≥ 2 unequivocally new MRI-detected lesions, or increased disability on examination over a one-year period

References

1. 1.     Briumvi [package Insert]. Morrisville, NC; TG Therapeutics, Inc.; December 2022. Accessed January 2023.
2. 2.     Steinman L, Fox E, Hartung HP, et al; ULTIMATE I and ULTIMATE II Investigators. Ublituximab versus Teriflunomide in Relapsing Multiple Sclerosis. N Engl J Med. 2022 Aug 25;387(8):704-714. doi: 10.1056/NEJMoa2201904.
3. 3.     Gawronski KM, Rainka MM, Patel MJ, Gengo FM. Treatment Options for Multiple Sclerosis: Current and Emerging Therapies. Pharmacotherapy. 2010; 30(9):916-927.
4. 4.     Goodin DS, Frohman EM, Garmany GP Jr, et al. Disease modifying therapies in multiple sclerosis: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines. Neurology. 2002 Jan 22; 58(2):169-78.
5. 5.     Freedman MS, Selchen D, Arnold DL, et al. Treatment optimization in MS: Canadian MS Working Group updated recommendations. Can J Neurol Sci. 2013 May;40(3):307-23.
6. 6.     Polman CH, Reingold SC, Banwell B, et al. Diagnostic criteria for multiple sclerosis: 2010 Revisions to the McDonald criteria. Ann Neurol. 2011 Feb; 69(2): 292–302. doi: 10.1002/ana.22366.
7. 7.     Lublin FD, Reingold SC, Cohen JA, et al. Defining the clinical course of multiple sclerosis: the 2013 revisions. Neurology. 2014 Jul 15;83(3):278-86.
8. 8.     Multiple Sclerosis Coalition. The use of disease-modifying therapies in multiple sclerosis: principles and current evidence. 2017 March. http://www.nationalmssociety.org/getmedia/5ca284d3-fc7c-4ba5-b005-ab537d495c3c/DMT_Consensus_MS_Coalition_color. Accessed 4/2018.
9. 9.     Rae-Grant, A, Day GS, Marrie RA, et al. Practice guideline recommendations summary: Disease-modifying therapies for adults with multiple sclerosis. Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology® 2018;90:777-788.
10. 10.  Thompson AJ, Banwell BL, Barkhof F, et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018 Feb;17(2):162-173. doi: 10.1016/S1474-4422(17)30470-2.
11. 11.  Kappos L, Bar-Or A, Cree BAC, et al. Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study. Lancet. 2018;391(10127):1263. Epub 2018 Mar 23.
12. 12.  Lorscheider J, Buzzard K, Jokubaitis V, et al, on behalf of the MSBase Study Group. Defining secondary progressive multiple sclerosis. Brain, Volume 139, Issue 9, September 2016, Pages 2395–2405, https://doi.org/10.1093/brain/aww173.
13. 13.  MICROMEDEX Healthcare Series. Drugdex Evaluations. (2023, January). Ublituximab-xiiy.  Retrieved January 2023 from MICROMEDEX Healthcare Series.    

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 and Blue Shield Association technology assessment program (TEC) and other nonaffiliated technology evaluation centers, reference to federal regulations, other plan medical policies, and accredited national guidelines.

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