Coverage Policy Manual - Arkansas Blue Cross and Blue Shield

Coverage Policy Manual

Policy #:

2023041

Category:

Pharmacy

Initiated:

September 2023

Last Review:

September 2025

Ublituximab-xiiy (e.g., Briumvi)

Description:

The policy applies to the following medication: Ublituximab-siiy (e.g., Briumvi).

Policy/
Coverage:

Prior Approval is required for ublituximab-siiy (e.g., Briumvi).

INITIAL AND CONTINUATION APPROVAL will be for duration of treatment course or 12 months (whichever comes first). Approval timeframes may differ for members/participants of Self-Insured plans.

Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria

INITIAL APPROVAL

Ublituximab-siiy (e.g., Briumvi) meets member benefit certificate Primary Coverage Criteria that there be scientific evidence of effectiveness in improving health outcomes or for members with contracts without Primary Coverage Criteria, is considered Medically Necessary and is covered, when ALL the following criteria are met:

Initial Approval and Continuation of Therapy:

Member receives a “recommended” determination from InterQual Criteria Ublituximab-siiy (e.g., Briumvi),

based on diagnosis and requested product. Click the following link to view the InterQual® criteria: https://prod.ds.interqual.com/service/connect/transparency?tid=27b0a724-ca06-4b22-846b-598b8dae52fc

Does Not Meet Primary Coverage Criteria Or Is Not Covered For Contracts Without Primary Coverage Criteria

Ublituximab-siiy (e.g., Briumvi) does not meet member benefit certificate Primary Coverage Criteria that there be scientific evidence of effectiveness in improving health outcomes and is not covered for any indication or circumstance not described above.

For contracts without Primary Coverage Criteria, Ublituximab-siiy (e.g., Briumvi), is considered not Medically Necessary and is not covered or is investigational for any indication or circumstance not described above. Not Medically Necessary or Investigational services are specific contract exclusions in most member benefit certificates of coverage.

Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.

Please refer to a separate policy on Maximum Dosage and Frequency (policy #2025031) for pharmacologic/biologic medications.

Effective November 15, 2025 to February 10, 2026

Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria

Ublituximab-siiy (e.g., Briumvi) meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes when ALL the following criteria are met:

INITIAL APPROVAL:

1. Individual 18 years of age or older (Briumvi,2022); AND

2. Individual has a diagnosis of one of the following forms of relapsing multiple sclerosis (MS):

a. Relapsing-remitting multiple sclerosis (MS); OR

b. Active secondary progressive MS; OR

c. Clinically isolated syndrome of MS; AND

3. Individual is not receiving any of the below drugs concurrently:

a. Disease modifying agents: interferon beta preparations, glatiramer acetate, natalizumab, fingolimod, cladribine, siponimod, ponesimod, ozanimod, teriflunomide; OR

b. Targeted B-cell agents: rituximab, belimumab, ofatumumab, ocrelizumab; OR

c. Lymphocyte blockers: alemtuzumab or mitoxantrone; AND

4. Individual has experienced at least two relapses within the previous two years OR one relapse within the previous year OR is switching from another disease modifying drug, targeted B-cell agent drug or lymphocyte blocker.

CONTINUATION OF THERAPY:

1. Individual previously met the above criteria and has received ublituximab; AND

2. Individual has documentation of clinical improvement or stabilization on ublituximab; AND

3. Individual is not receiving any of the below drugs concurrently:

a. Disease modifying agents: interferon beta preparations, glatiramer acetate, natalizumab, fingolimod, cladribine, siponimod, teriflunomide; OR

b. Targeted B-cell agents: rituximab, belimumab, ofatumumab, ocrelizumab; OR

c. Lymphocyte blockers: alemtuzumab or mitoxantrone

Does Not Meet Primary Coverage Criteria Or Is Not Covered For Contracts Without Primary Coverage Criteria

Ublituximab-xiiy (e.g., Briumvi), for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.

For members with contracts without primary coverage criteria, ublituximab-xiiy (e.g., Briumvi), for any indication or circumstance not described above, is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.

POLICY GUIDELINES

Prescribing provider responsible for ensuring individual does not have an active serious infection including Hepatitis B (Briumvi, 2022).

DOSAGE AND ADMINISTRATION

For FDA labeled indications, Ublituximab-siiy (e.g., Briumvi) must be dosed in accordance with the indication specific recommended dose per FDA label unless otherwise specified below.

Administer ublituximab-xiiy by intravenous infusion.

First Infusion: 150 mg intravenous infusion
Second Infusion: 450 mg intravenous infusion two weeks after the first infusion
Subsequent Infusions: 450 mg intravenous infusion 24 weeks after the first infusion and every 24 weeks thereafter

Ublituximab-xiiy is available as 150 mg/6 mL (25 mg/mL) in a single-dose vial.

Please refer to separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.

Effective January 1, 2025 to November 14, 2025

Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria

INITIAL APPROVAL STANDARD REVIEW for up to 12 months:

1. Individual 18 years of age or older (Briumvi,2022); AND

2. Individual has a diagnosis of one of the following forms of relapsing multiple sclerosis (MS):

a. Relapsing-remitting multiple sclerosis (MS); OR

b. Active secondary progressive MS; OR

c. Clinically isolated syndrome of MS; AND

3. Individual has no evidence of active infection with hepatitis B (Briumvi, 2022); AND

4. Individual is not receiving any of the below drugs concurrently:

a. Disease modifying agents: interferon beta preparations, glatiramer acetate, natalizumab, fingolimod, cladribine, siponimod, ponesimod, ozanimod, teriflunomide; OR

b. Targeted B-cell agents: rituximab, belimumab, ofatumumab, ocrelizumab; OR

c. Lymphocyte blockers: alemtuzumab or mitoxantrone; AND

5. Individual has no evidence of serious active infection; AND

6. Individual has experienced at least two relapses within the previous two years or one relapse within the previous year; AND

7. Must be dosed in accordance with the FDA label.

CONTINUED APPROVAL for up to 1 year:

1. Individual previously met the above criteria and has received ublituximab; AND

2. Individual has documentation of clinical improvement or stabilization on ublituximab; AND

3. Individual is not receiving any of the below drugs concurrently:

a. Disease modifying agents: interferon beta preparations, glatiramer acetate, natalizumab, fingolimod, cladribine, siponimod, teriflunomide; OR

b. Targeted B-cell agents: rituximab, belimumab, ofatumumab, ocrelizumab; OR

c. Lymphocyte blockers: alemtuzumab or mitoxantrone; AND

4. Must be dosed in accordance with the FDA label.

Dosage and Administration

Dosing per FDA Guidelines

Administer ublituximab-xiiy by intravenous infusion.

1. First Infusion: 150 mg intravenous infusion

2. Second Infusion: 450 mg intravenous infusion two weeks after the first infusion

3. Subsequent Infusions: 450 mg intravenous infusion 24 weeks after the first infusion and every 24 weeks thereafter

Ublituximab-xiiy is available as 150 mg/6 mL (25 mg/mL) in a single-dose vial.

Please refer to separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.

Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria

Ublituximab-xiiy, for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.

For members with contracts without primary coverage criteria, ublituximab-xiiy, for any indication or circumstance not described above, is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.

Effective Date September 20, 2023 to December 31, 2024

Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria

INITIAL APPROVAL STANDARD REVIEW for up to 12 months:

Ublituximab-xiiy meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for the following conditions:

Relapsing-remitting multiple sclerosis (MS); OR
Active secondary progressive MS; OR
Clinically isolated syndrome of MS; AND
ALL of the following criteria are met:

a. Age greater than or equal to 18 years old; AND

b. No evidence of active infection with hepatitis B; AND

c. Prior to initiation, perform testing for quantitative serum immunoglobulins. For individuals with hypogammaglobulinemia, monitoring and treatment plan required with suggestion of immunology consult before initiating treatment; AND

d. No history of prior life-threatening infusion reactions to ublituximab; AND

5. Individual is not receiving any of the below drugs concurrently:

a. Disease modifying agents: interferon beta preparations, glatiramer acetate, natalizumab, fingolimod, cladribine, siponimod, teriflunomide; OR

b. Targeted B-cell agents: rituximab, belimumab, ofatumumab, ocrelizumab; OR

c. Lymphocyte blockers: alemtuzumab or mitoxantrone; AND

6. Individual has experienced at least two relapses within the previous two years or one relapse within the previous year; AND

7. Individual has least one T1 gadolinium-enhancing lesion on MRI within the previous year OR significant increase in T2 lesion load compared with a previous MRI; AND

8. Must be dosed in accordance with the FDA label.

CONTINUED APPROVAL for up to 1 year:

Previously met the above criteria and has received ublituximab; AND
Documentation of clinical improvement or stabilization on ublituximab; AND
Individual is not receiving any of the below drugs concurrently:

a. Disease modifying agents: interferon beta preparations, glatiramer acetate, natalizumab, fingolimod, cladribine, siponimod, teriflunomide; OR

b. Targeted B-cell agents: rituximab, belimumab, ofatumumab, ocrelizumab; OR

c. Lymphocyte blockers: alemtuzumab or mitoxantrone.

Dosage and Administration

Dosing per FDA Guidelines

Administer ublituximab-xiiy by intravenous infusion.

First Infusion: 150 mg intravenous infusion
Second Infusion: 450 mg intravenous infusion two weeks after the first infusion
Subsequent Infusions: 450 mg intravenous infusion 24 weeks after the first infusion and every 24 weeks thereafter

Ublituximab-xiiy is available as 150 mg/6 mL (25 mg/mL) in a single-dose vial.

Please refer to separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.

Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria

Rationale:

Ublituximab for patients with relapsing MS has been studied in two identical randomized trials, ULTIMATE I (n = 549) and ULTIMATE II (n = 545). Patients in these trials were randomly assigned in a 1:1 ratio to intravenous ublituximab (150 mg on day one, followed by 450 mg on day 15 and at weeks 24, 48, and 72) plus oral placebo, or to oral teriflunomide (14 mg daily) plus intravenous placebo. At a median follow-up of 95 weeks, the annualized relapse rate was lower with ublituximab compared with teriflunomide in ULTIMATE I (0.08 versus 0.19; rate ratio [RR] 0.41, 95% CI 0.27-0.62) and ULTIMATE II (0.09 versus 0.18; RR 0.51, 95% CI 0.33-0.78). The mean number of gadolinium-enhancing brain lesions on MRI was also lower with ublituximab compared with teriflunomide in ULTIMATE I (0.02 versus 0.49; RR 0.03, 95% CI 0.02-0.06) and ULTIMATE II (0.01 versus 0.25; RR 0.04, 95% CI 0.02-0.06).

In a pooled analysis of the two trials, worsening of disability at 12 weeks was similar with ublituximab and teriflunomide (5.2 versus 5.9 percent, hazard ratio 0.84; 95% CI 0.50-1.41).

2024 Update

Annual policy review completed with a literature search using the MEDLINE database through July 2024.

2025 Update

Annual policy review completed with a literature search using the MEDLINE database through September 2025.

CPT/HCPCS:

References:

Briumvi(2022) package insert Morrisville, NC: TG Therapeutics, Inc; 2022.

de Romeuf C, Dutertre CA, Le Garff-Tavernier M, et al.(2008) Chronic lymphocytic leukemia cells are efficiently killed by an anti-CD20 monoclonal antibody selected for improved engagement of FcgammaRIIIA/CD16. Br J Haematol 2008; 140:635.

Food and Drug Administration(2022) Briumvi (ublituximab-xiiy) injection, for intravenous use; labelling - package insert. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761238s000lbl.pdf.

Steinman L, Fox E, Hartung HP, et al.(2022) Ublituximab versus Teriflunomide in Relapsing Multiple Sclerosis. N Engl J Med 2022; 387:704.

Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants.