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Ublituximab-xiiy (Briumvi®) for intravenous use
08.02.02b

Policy

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.

MEDICALLY NECESSARY

Ublituximab-xiiy (Briumvi®​) is considered medically necessary and, therefore, covered for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome (CIS), relapsing-remitting multiple sclerosis (RRMS), and active secondary progressive multiple sclerosis (SPMS), in adults when all​ of the following are met:
  • The individual has a confirmed diagnosis of relapsing MS (RMS) 
  • The individual has active disease 
  • The individual does not have a diagnosis of primary progressive MS (PPMS)
EXPERIMENTAL/INVESTIGATIONAL

All other uses for ublituximab-xiiy (Briumvi) 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 service.

Guidelines

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, ublituximab-xiiy (Briumvi) is covered under the medical benefits of the Company's products when the medical necessity criteria listed in this medical policy are met.

DOSING

The dosing of ublituximab-xiiy (Briumvi) is as follows:​
  • Initial dose: 150 mg intravenous (IV) infusion
  • Second dose: 450 mg IV infusion administered 2 weeks after the first infusion
  • Subsequent doses: 450 mg  IV infusion administered 24 weeks after the first infusion and every 24 weeks thereafter
  • Observe the individual for at least 1 hour after completion of the first two infusions. Post-infusion monitoring of subsequent infusions is at the provider's discretion unless infusion reaction and/or hypersensitivity has been observed in association with the current or any prior infusion.​
US FOOD AND DRUG ADMINISTRATION STATUS

Ublituximab-xiiy (Briumvi) was approved by the US Food and Drug Administration (FDA) on December 28, 2022, for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome (CIS), relapsing-remitting multiple sclerosis (RRMS), and active secondary progressive multiple sclerosis (SPMS), in adults.

PEDIATRIC USE
The safety and effectiveness of ublituximab-xiiy (Briumvi) have not been established in pediatric individuals.

Description

Multiple sclerosis (MS) is a disease that disrupts the flow of information in the central nervous system (CNS), which affects the brain, spinal cord, and optic nerves in individuals with MS. A triggering event causes the individual's immune system to attack the CNS, resulting in damage to the outer protective layer, called myelin, of the CNS system. This results in unpredictable disruptions in the flow of signals from the brain to the body along the CNS pathways. Some common symptoms are fatigue, numbness/tingling, pain, paralysis, mood changes, and memory problems. A 2019 study found that nearly 1 million people in the United States are living with MS. The exact cause of MS is not known. Most individuals who are diagnosed with MS are between 20 and 50 years old, and most are female. Each individual with MS experiences the disease differently, but there are four basic types of MS: clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS), primary progressive MS (PPMS), and secondary progressive MS (SPMS).

CIS is the first episode of neurological symptoms, which lasts for at least 24 hours, in an individual. The episode does not meet the diagnosis of MS because the individual who experiences CIS may not go on to develop MS. If CIS is accompanied with identifiable CNS lesions on a magnetic resonance imaging (MRI) scan, it is more likely that the individual will later be diagnosed with MS. There are some therapies approved for CIS that can delay the onset of MS.

RRMS is the most common course of the disease in individuals diagnosed with MS. This disease course type is characterized by clearly defined exacerbations (relapses) of new or increasing neurological symptoms that are followed by periods of complete or partial recovery (remissions). The disease may be active (with or without MRI activity) or not active, and the symptoms may worsen or not worsen during each episode.

PPMS is the course of MS characterized by the lack of early relapses or remissions as the neurological functioning worsens. PPMS can be further classified as active (with or without MRI activity) or not active, as well as with progression or without progression. The individual may have brief periods of stable disease as well as periods of increasing disability with or without new relapses or MRI activity.

SPMS is the progression of MS after a time of RRMS. Some individuals with RRMS will transition to SPMS. This course of the disease is characterized by a progressive worsening of CMS function, with the accumulation of disability, over time. This course of the disease can also be further classified as active (with or without MRI activity) or not active, as well as with progression or without progression. During this course of the disease, the individual may still occasionally experience relapses as well as times of stable disease.

Ublituximab-xiiy (Briumvi) is a recombinant chimeric monoclonal immunoglobulin (Ig) G1 antibody directed against cluster of differentiation (CD)20-expressing B cells. The precise mechanism by which ublituximab-xiiy (Briumvi) exerts its therapeutic effects in MS 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 (Briumvi) results in cell lysis through mechanisms including antibody-dependent cellular cytolysis and complement-dependent cytolysis.

The safety and efficacy of ublituximab-xiiy (Briumvi) was evaluated in two identical, simultaneously run clinical trials: NCT03277261 (ULTIMATE 1) and NCT03277248 (ULTIMATE 2). The clinical trials were phase III, randomized, multicenter, double-blinded, active-controlled studies comparing individuals who received intravenous (IV) ublituximab-xiiy (Briumvi) and oral placebo versus individuals who received IV placebo and oral teriflunomide (Aubagio). The primary endpoint was the annualized relapse rate (ARR). Some secondary endpoints included total number of gadolinium (Gd)-enhancing T1 lesions per MRI scan, total number of new and enlarging T2 hyperintense lesions per MRI scan, and time to confirmed disability progression (CDP) for at least 12 weeks.

In ULTIMATE 1, 271 individuals were randomly assigned to receive ublituximab-xiiy (Briumvi) and 274 individuals received teriflunomide (Aubagio). The ARR for the ublituximab-xiiy (Briumvi) cohort was 0.076 versus 0.188 for the teriflunomide (Aubagio) cohort, which represented a 59 percent relative reduction rate (P<0.001). The mean number of T1 Gd-enhancing lesions in the ublituximab-xiiy (Briumvi) cohort was 0.016 versus 0.491 for the teriflunomide (Aubagio) cohort, which represented a 97 percent relative reduction rate (P<0.001). The mean number of new or enlarging T2 hyperintense lesions for the ublituximab-xiiy (Briumvi) cohort was 0.213 versus 2.789 for the teriflunomide (Aubagio) cohort, which represented a 92 percent relative reduction rate (P<0.001).

In ULTIMATE 2, 272 individuals were randomly assigned to receive ublituximab-xiiy (Briumvi) and 272 individuals received teriflunomide (Aubagio). The ARR for the ublituximab-xiiy (Briumvi) cohort was 0.091 versus 0.178 for the teriflunomide (Aubagio) cohort, which represented a 49 percent relative reduction rate (P=0.002). The mean number of T1 Gd-enhancing lesions in the ublituximab-xiiy (Briumvi) cohort was 0.009 versus 0.250 for the teriflunomide (Aubagio) cohort, which represented a 97 percent relative reduction rate (P<0.001). The mean number of new or enlarging T2 hyperintense lesions for the ublituximab-xiiy (Briumvi) cohort was 0.282 versus 2.831 for the teriflunomide (Aubagio) cohort, which represented a 90 percent relative reduction rate (P<0.001). The proportion of individuals with 12-week CDP risk reduction (pooled analysis between ULTIMATE 1 and ULTIMATE 2) was 5.2 percent for the ublituximab-xiiy (Briumvi) cohort versus 5.9 percent for the teriflunomide (Aubagio) cohort, which was an insignificant change (16 percent; ​P=0.510).
 
OFF-LABEL INDICATION

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

American Hospital Formulary Service (AHFS). Ublituximab-xiiy (Briumvi®). AHFS Drug Information 2025. [LexiComp Web site]. 02/17/2025. Available at: https://online.lexi.com/lco/action/home [via subscription only]. Accessed May 12, 2025.

Briumvi® (ublituximab-xiiy). [prescribing information]. Morrisville, NC: TG Therapeutics, Inc. 10/2024. Available at: https://www.tgtherapeutics.com/. Accessed May 12, 2025.

ClinicalTrials.gov. Study to assess the efficacy and safety of ublituximab in participants with relapsing forms of multiple sclerosis (RMS) (ULTIMATE 1). ClinicalTrials.gov Identifier: NCT03277261. First Posted: September 11, 2017. Last Update Posted: December 6, 2021. Available at: https://clinicaltrials.gov/. Accessed May 12, 2025.

ClinicalTrials.gov. Study to assess the efficacy and safety of ublituximab in participants with relapsing forms of multiple sclerosis (RMS) (ULTIMATE II). ClinicalTrials.gov Identifier: NCT03277248. First Posted: September 11, 2017. Last Update Posted: December 6, 2021. Available at: https://clinicaltrials.gov/. Accessed May 12, 2025.

Elsevier's Clinical Pharmacology Compendium. Ublituximab-xiiy (Briumvi®). [Clinical Key Web site]. 04/29/2025. Available at: https://www.clinicalkey.com/#!/ [via subscription only]. Accessed May 12, 2025.

Merative Micromedex® DRUGDEX® (electronic version). Ublituximab-xiiy (Briumvi®). [Micromedex Web site]. Merative L.P., Ann Arbor, Michigan, USA. 01/30/2025. Available at: https://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed May 12, 2025.

National Multiple Sclerosis Society. [National Multiple Sclerosis Society web site]. 2025. Available at: https://www.nationalmssociety.org/. Accessed May 12, 2025.

Olek MJ, Mowry E. Initial disease-modifying therapy for relapsing-remitting multiple sclerosis in adults. [UpToDate Web site]. 01/10/2025. Available at: https://www.uptodate.com/contents/initial-disease-modifying-therapy-for-relapsing-remitting-multiple-sclerosis-in-adults?search=ublituximab&source=search_result&selectedTitle=4~7&usage_type=default&display_rank=3. Accessed May 12, 2025.

Steinman L, Fox E, Hartung HP, et al. Ublituximab versus teriflunomide in relapsing multiple sclerosis. N Engl J Med. 2022;387(8):704-704.

UpToDate® LexidrugTM. Ublituximab-xiiy (Briumvi®). [UpToDate Lexidrug Web site]. 05/05/2025. Available at: https://online.lexi.com/lco/action/home [via subscription only]. Accessed May 12, 2025.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Ublituximab-xiiy (Briumvi®). Prescribing information. [FDA Web site]. 10/30/2024. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm. Accessed May 12, 2025. ​

Coding

CPT Procedure Code Number(s)
N/A
ICD - 10 Procedure Code Number(s)
N/A
ICD - 10 Diagnosis Code Number(s)

G35.A Relapsing-remitting multiple sclerosis​

G35.C1 Active secondary progressive multiple sclerosis

G35.D Multiple sclerosis, unspecified


HCPCS Level II Code Number(s)

J2329 Injection, ublituximab-xiiy, 1mg

Revenue Code Number(s)
N/A

Coding and Billing Requirements

Policy History


Revisions From 08.02.02b:
10/01/2025
​This version of the policy will become effective 10/01/2025.
 
Inclusion of a policy in a Code Update memo does not imply that a full review of
the policy was completed at this time.
 
The following ICD-10 codes have been added to this policy:
G35.A Relapsing-remitting multiple sclerosis
G35.C1 Active secondary progressive multiple sclerosis​
G35.D Multiple sclerosis, unspecified​
 
The following ICD-10 code has been removed from this policy:
G35 Multiple sclerosis​

Revisions From 08.02.02a:
07/09/​2025
​The policy has been reviewed and reissued to communicate the Company’s continuing position on ublituximab-xiiy (Briumvi®).​
​03/06/2024

​The policy has been reviewed and reissued to communicate the Company’s continuing position on ublituximab-xiiy (Briumvi®).

07/01/2023

This version of the policy will become effective 07/01/2023.

Inclusion of a policy in a Code Update memo does not imply that a full review of
the policy was completed at this time.

The following HCPCS codes have been removed from this policy:

C9399 Unclassified drugs or biologicals

J3590 Unclassified biol​ogics​

The following HCPCS code has been added to this policy:

J2329 Injection, ublituximab-xiiy​, 1 mg


Revisions From 08.02.02:
03/13/2023
The following new policy has been developed to communicate the Company’s coverage criteria for ublituximab-xiiy (BriumviTM) for intravenous use​. The policy will become effective 03/13/2023.​

10/1/2025
10/1/2025
08.02.02
Medical Policy Bulletin
Commercial
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