Notification



Notification Issue Date:



Medical Policy Bulletin


Title:Belimumab (Benlysta®) for Intravenous Use

Policy #:08.00.99c



The Company makes decisions on coverage based on Policy Bulletins, benefit plan documents, and the member’s medical history and condition. Benefits may vary based on contract, and individual member benefits must be verified. The Company determines medical necessity only if the benefit exists and no contract exclusions are applicable.

When services can be administered in various settings, 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. This decision is based on the member’s current medical condition and any required monitoring or additional services that may coincide with the delivery of this service.

This Medical Policy Bulletin document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy Bulletin will be reviewed regularly and be updated as scientific and medical literature becomes available. For more information on how Medical Policy Bulletins are developed, go to the About This Site section of this Medical Policy Web site.



Policy

Coverage is subject to the terms, conditions, and limitations of the member's contract.

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

Belimumab (Benlysta®) for intravenous use is considered medically necessary and, therefore, covered when used for the treatment of individuals five years of age and older who meet all of the following criteria:
  • Active systemic lupus erythematosus (SLE)
  • Positive autoantibody test (e.g., antinuclear antibody test [ANA], antibodies to DNA [Anti-dsDNA], Anti-Smith [Anti-Sm])
  • Concurrent treatment with at least one of the following: steroids, antimalarials, immunosuppressives, or nonsteroidal anti-inflammatory drugs (NSAIDS)

EXPERIMENTAL/INVESTIGATIONAL

Belimumab (Benlysta®) for intravenous use is considered experimental/investigational and, therefore, not covered because the safety and/or effectiveness of this service cannot be established by review of the available published peer-reviewed literature in the following clinical circumstances:
  • In individuals with severe, active lupus nephritis or severe, active central nervous system lupus
  • In combination with other biologics or intravenous cyclophosphamide

All other uses for belimumab (Benlysta®) for intravenous use 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 drug.

BILLING REQUIREMENTS

For drugs that have more than one method of administration, application of the JA modifier is required to indicate the route of administration.
  • To report the intravenous route of administration, append the following modifier: JA Administered Intravenously

Inclusion of a code in this policy does not imply reimbursement. Eligibility, benefits, limitations, exclusions, utilization management/referral requirements, provider contracts, and Company policies apply.
Guidelines

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, belimumab (Benlysta®) for intravenous use is covered under the medical benefits of the Company's products when the medical necessity criteria listed in this medical policy are met.

However, services that are identified in this policy as experimental/investigational are not eligible for coverage or reimbursement by the Company.

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

Belimumab (Benlysta®) for intravenous use was approved by the FDA on March 9, 2011 for the treatment of adult patients with active, autoantibody-positive, systemic lupus erythematosus who are receiving standard therapy. Supplemental approvals for belimumab (Benlysta®) for intravenous use have since been issued by the FDA. The efficacy of belimumab (Benlysta®) for intravenous use has not been evaluated in individuals with severe active lupus nephritis or severe active central nervous system lupus. Belimumab (Benlysta®) for intravenous use has not been studied in combination with other biologics or intravenous cyclophosphamide. Use of belimumab (Benlysta®) for intravenous use is not recommended in these situations.

PEDIATRIC INDIVIDUALS
Intravenous administration of belimumab (Benlysta®) is indicated in individuals aged five years and older; its safety and effectiveness have not been established in pediatric individuals younger than five years of age. The safety and effectiveness of subcutaneous administration of belimumab (Benlysta®) have not been established in pediatric individuals younger than 18 years of age.

Description

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by periods of illness and remissions in which the immune system produces antibodies to cells within the body leading to widespread inflammation and tissue damage. Immunologic abnormalities, especially the production of a number of antinuclear antibodies (ANA), are a prominent feature of the disease. SLE has a variety of clinical manifestations, and it can affect joints, skin, brain, lungs, kidneys, and blood vessels. Individuals with SLE may experience fatigue, pain or swelling in joints, skin rashes, and fevers.

On March 9, 2011, the US Food and Drug Administration (FDA) approved belimumab (Benlysta®) for intravenous use, an intravenously delivered agent, for use in individuals with active, autoantibody-positive lupus (systemic lupus erythematosus [SLE]) who are receiving standard therapy, including corticosteroids, antimalarials, immunosuppressives, and nonsteroidal anti-inflammatory drugs (NSAIDs). It is the first inhibitor intended to target B-lymphocyte stimulator (BLyS) protein, which may reduce the number of abnormal B cells. BLyS is overexpressed in patients with systemic lupus erythematosus (SLE) and other autoimmune diseases. After subsequent studies using the intravenous formulation, the FDA granted approval in pediatric individuals age five years and older. Additionally, a subcutaneous formulation of belimumab (Benlysta®) for use in adults was also FDA approved.

PEER-REVIEWED LITERATURE

SUMMARY
Two clinical studies involving 1,684 individuals with lupus demonstrated the safety and effectiveness of belimumab (Benlysta®) for intravenous use. The studies diagnosed individuals with active lupus and randomized them to receive belimumab (Benlysta®) for intravenous use plus standard therapy, or an inactive infused solution (placebo) plus standard therapy. The studies excluded anyone who had received prior B-cell targeted therapy or intravenous cyclophosphamide, and those who had active lupus involving the kidneys or central nervous system.

The individuals treated with belimumab (Benlysta®) for intravenous use and standard therapies experienced less disease activity than those who received a placebo and standard-of-care medicines. Results suggested, but did not definitively establish, that some patients had a reduced likelihood of severe flares, and some reduced their steroid doses.

Subsequent safety and efficacy results for subjects treated up to seven years continue to support disease control and safety profile in individuals with active SLE taking belimumab plus standard therapy.

OFF-LABEL INDICATIONS

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

Belimumab (Benlysta). American Hospital Formulary Service (AHFS). Drug Information. [Lexicomp Web site]. 12/21/2011. Available at: http://online.lexi.com/lco/action/doc/retrieve/docid/essential_ashp/5072084 [via subscription only]. Accessed March 20, 2020.


Belimumab (Benlysta). Elsevier’s Clinical Pharmacology Compendium. 05/03/2019. [Clinical Key Web site]. Available at: https://www.clinicalkey.com/pharmacology/ [via subscription only]. Accessed March 20, 2020.

Belimumab (Benlysta). Lexi-Drugs Compendium. 01/27/2020. [Lexicomp Online Web site]. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed March 20, 2020.

Belimumab (Benlysta). Micromedex® DrugDex® Compendium. [Micromedex® Solutions Web site]. 11/06/2019. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed March 20, 2020.

Bishton M, Spencer A, Dickinson M, et al. A single-arm, phase II study of the anti-Blys monoclonal antibody belimumab in symptomatic Waldenstrom macroglobulinemia. Clin Lymphoma Myeloma Leuk. 2013;13(5):575-8.

Dooley MA, Houssiau F, Aranow C, et al. Effect of belimumab treatment on renal outcomes: results from the phase 3 belimumab clinical trials in patients with SLE. Lupus. 2013;22(1):63-72.

Furie R, Stohl W, Ginzler EM, et al. Biologic activity and safety of belimumab, a neutralizing anti-B-lymphocyte stimulator (BLyS) monoclonal antibody: a phase I trial in patients with systemic lupus erythematosus. Arthritis Res Ther.2008;10(5):R109.

Ginzler EM, Wallace DJ, Merrill JT, et al. Disease control and safety of belimumab plus standard therapy over 7 years in patients with systemic lupus erythematosus. J Rheumatol. 2014;41(2):300-9.

Human Genome Sciences, Rockville MD. and GlaxoSmithKline, Research Triangle Park, NC. Benlysta® (belimumab) Prescribing Information. 01/2020. Available at: https://www.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_Information/Benlysta/pdf/BENLYSTA-PI-MG.PDF. Accessed March 20, 2020.

Lateef A, Petri M. Biologics in the treatment of systemic lupus erythematosus. Curr Opin Rheumatol. 2010;22(5):504-509.

Lutalo PM, D'Cruz DP. Update on belimumab for the management of systemic lupus erythematosus. Expert Opin Biol Ther. 2014;14(11):1701-8.

Mariette X, Seror R, Quartuccio L, et al. Efficacy and safety of belimumab in primary Sjögren's syndrome: results of the BELISS open-label phase II study. Ann Rheum Dis. 2015;74(3):526-31.

Navarra S, Buzman R, Gallacher A, et al. Belimumab, a BLyS-specific inhibitor, reduces disease activity and flares, and predinosone use in patients with active SLE: efficacy and safety results from the phase 3 BLISS-52 study. Late Breaking Abstract B L1. Presented at the ACR/ARHP meeting. 2009.

Navarra SV, Guzmán RM, Gallacher AE, et al. Efficacy and safety of belimumab in patients with active systemic lypus erythematosus: a randomized, placebo-controlled, phase 3 trial. Lancet. 2011;377(9767):721:-731.

Novitas Solutions, Inc. Article (A53127) For Self-Administered Drug Exclusion List. [Novitas Medicare Services Web site]. Original: 10/01/2015, Revised: 12/02/2019. Available at:
https://www.cms.gov/medicare-coverage-database/details/article-details.aspx?articleId=53127&ver=88&name=331*1&UpdatePeriod=855&bc=AAAAEAAAAAAA&. Accessed March 20, 2020.

Novitas Solutions, Inc. FUTURE Article (A53127) For Self-Administered Drug Exclusion List. [Novitas Medicare Services Web site]. Original: 10/01/2015, Revised: 05/03/2020. Available at:
https://www.cms.gov/medicare-coverage-database/details/article-details.aspx?articleId=53127&ver=96&name=331*1&UpdatePeriod=877&bc=AAAACAAAAAAA&. Accessed March 23, 2020.

Singh JA, Noorbaloochi S, Tucker MD. Belimumab for systemic lupus erythematosus (Protocol). Cochrane Database of Systematic Reviews 2013, Issue 7. Art. No.: CD010668.

Stohl W, Merrill JT, McKay JD, et al. Efficacy and safety of belimumab in patients with rheumatoid arthritis: a phase II, randomized, double-blind, placebo-controlled, dose-ranging Study. J Rheumatol. 2013;40(5):579-89.

Thanou-Stavrakil A, Sawalha H. An update on belimumab for the treatment of lupus. Biologics. 2011;5:33-43.

van Vollenhoven RF, Zamani O, Wallace DJ, et al. Belimumab, a BLyS-Specific inhibitor, reduces disease activity and severe flares in seropositive SLE patients: BLISS-76 study. Ann Rheum Dis. 2010;69(suppl 3):74.

Wallace DJ, Navarra S, Petri MA, et al. Safety profile of belimumab: pooled data from placebo-controlled phase 2 and 3 studies in patients with systemic lupus erythematosus. Lupus. 2013;22(2):144-54.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Belimumab (Benlysta). Approval letter and prescribing information. [FDA web site]. 01/17/2020. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed March 20, 2020.



Coding

Inclusion of a code in this table does not imply reimbursement. Eligibility, benefits, limitations, exclusions, precertification/referral requirements, provider contracts, and Company policies apply.

The codes listed below are updated on a regular basis, in accordance with nationally accepted coding guidelines. Therefore, this policy applies to any and all future applicable coding changes, revisions, or updates.

In order to ensure optimal reimbursement, all health care services, devices, and pharmaceuticals should be reported using the billing codes and modifiers that most accurately represent the services rendered, unless otherwise directed by the Company.

The Coding Table lists any CPT, ICD-9, ICD-10, and HCPCS billing codes related only to the specific policy in which they appear.

CPT Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD - 10 Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD -10 Diagnosis Code Number(s)

M32.0 Drug-induced systemic lupus erythematosus

M32.10 Systemic lupus erythematosus, organ or system involvement unspecified

M32.11 Endocarditis in systemic lupus erythematosus

M32.12 Pericarditis in systemic lupus erythematosus

M32.13 Lung involvement in systemic lupus erythematosus

M32.14 Glomerular disease in systemic lupus erythematosus

M32.15 Tubulo-interstitial nephropathy in systemic lupus erythematosus

M32.19 Other organ or system involvement in systemic lupus erythematosus

M32.8 Other forms of systemic lupus erythematosus

M32.9 Systemic lupus erythematosus, unspecified



HCPCS Level II Code Number(s)

J0490 Injection, Belimumab 10 mg


Revenue Code Number(s)

N/A


Misc Code

:


THE FOLLOWING MODIFIER IS USED WHEN REPORTING
Belimumab (Benlysta®) for Intravenous Use

JA Intravenous administration



Coding and Billing Requirements

For drugs that have more than one method of administration, application of the JA modifier is required to indicate the route of administration.
  • To report the intravenous route of administration, append the following modifier: JA Administered Intravenously

Inclusion of a code in this policy does not imply reimbursement. Eligibility, benefits, limitations, exclusions, utilization management/referral requirements, provider contracts, and Company policies apply.
Cross References


Policy History

REVISIONS FROM 08.00.99c:
06/08/2020This version of the policy will become effective 06/08/2020.

This policy was updated to include coverage for belimumab (Benlysta®) in pediatric individuals five years of age or older, in accordance with US Food and Drug Administration labeling. A Billing Requirement was added to this policy regarding the Coding Modifier: JA Intravenous administration.

REVISIONS FROM 08.00.99b:
03/27/2019The policy has been reviewed and reissued to communicate the Company’s continuing position on Belimumab (Benlysta®) for intravenous use.
03/28/2018This policy has been reissued in accordance with the Company's annual Policy Confirmation Review track. The references were updated accordingly. The policy was updated to be consistent with current template wording and format. The adoptable source for this policy is FDA labeling (07/2017), Micromedex (10/2017), and AHFS (3/2017).

Effective 10/05/2017 this policy has been updated to the new policy template format.
Version Effective Date: 06/08/2020
Version Issued Date: 06/08/2020
Version Reissued Date: N/A



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