Notification



Notification Issue Date:



Medicare Advantage Policy

Title:Ibalizumab-uiyk (Trogarzo™)
Policy #:MA08.096a

This policy is applicable to the Company’s Medicare Advantage products only. Policies that are applicable to the Company’s commercial products are accessible via a separate commercial policy database.


The Company makes decisions on coverage based on the Centers for Medicare and Medicaid Services (CMS) regulations and guidance, benefit plan documents and contracts, and the member’s medical history and condition. If CMS does not have a position addressing a service, the Company makes decisions based on Company Policy Bulletins. 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. Although the Medicare Advantage Policy Bulletin is consistent with Medicare’s regulations and guidance, the Company’s payment methodology may differ from Medicare.

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 Policy Bulletin document describes the status of CMS coverage, medical terminology, and/or benefit plan documents and contracts at the time the document was developed. This Policy Bulletin will be reviewed regularly and be updated as Medicare changes their regulations and guidance, scientific and medical literature becomes available, and/or the benefit plan documents and/or contracts are changed.



Policy

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

MEDICALLY NECESSARY

Ibalizumab-uiyk (Trogarzo™) is considered medically necessary and, therefore, covered for the treatment of human immunodeficiency virus type 1 (HIV-1) infection when all of the following criteria are met:
  • Individual is 18 years of age or older.
  • Documentation of viral load greater than 200 copies/mL.
  • Individual has multi-drug--resistant HIV characterized by both of the following features:
    • Individual has received anti-retroviral regimens for at least 6 months.
    • Documentation of resistance to at least one combination of antiretroviral medications from any of the following classes of antiretroviral medications, as measured by genotypic/phenotypic resistance testing:
      • Nucleoside reverse transcriptase inhibitor (NRTI) (e.g., abacavir [Ziagen], lamivudine [Epivir], tenofovir [Viread], emtricitabine [Emtriva])
      • Non-nucleoside reverse transcriptase inhibitor (NNRTI) (e.g., efavirenz [Sustiva], etravirine [Intelence], nevirapine [Viramune], rilpivirine [Edurant])
      • Protease inhibitor (PI) (e.g., atazanavir [Reyataz], darunavir [Prezista], ritonavir [Norvir])
      • Integrase strand transfer inhibitor (INSTI) (e.g., dolutegravir (Tivicay), elvitegravir [Vitekta], raltegravir [Isentress])
      • Chemokine coreceptor CCR5 antagonist (e.g., maraviroc [Selzentry])
      • Fusion inhibitor (e.g., enfuviritide [Fuzeon])
  • Ibalizumab-uiyk (Trogarzo™) will be used concomitantly with at least one antiretroviral drug to which the individual's virus is susceptible (i.e., optimized background regimen).

CONTINUATION THERAPY
Continuation of ibalizumab-uiyk (Trogarzo™) therapy is considered medically necessary and, therefore, covered when both of the following criteria are met:
  • Continued or sustained reduction in viral load, measured at least every six months
  • Concomitant administration with at least one antiretroviral drug to which the individual's virus is susceptible (i.e., optimized background regimen)

EXPERIMENTAL/INVESTIGATIONAL

All other uses for ibalizumab-uiyk (Trogarzo™) 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.
Policy Guidelines

BENEFIT APPLICATION

Subject to the applicable Evidence of Coverage, ibalizumab-uiyk (Trogarzo™) is covered under the medical benefits of the Company’s Medicare Advantage products when the medical necessity criteria listed in this medical policy are met.

There is no Medicare coverage determination addressing this drug; therefore, the Company policy is applicable.

For Medicare Advantage members, certain drugs are available through either the member's medical benefit (Part B benefit) or pharmacy benefit (Part D benefit), depending on how the drug is prescribed, dispensed, or administered. This medical policy only addresses instances when ibalizumab-uiyk (Trogarzo™) is covered under a member's medical benefit (Part B benefit). It does not address instances when ibalizumab-uiyk (Trogarzo™) is covered under a member’s pharmacy benefit (Part D benefit).

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

Ibalizumab-uiyk (Trogarzo™) was approved by the FDA on March 6, 2018 for the treatment of human immunodeficiency virus type 1 (HIV-1) infection, in combination with other antiretroviral(s), in heavily treatment-experienced adults with multidrug resistant HIV-1 infection failing their current antiretroviral regimen.

PEDIATRIC USE

The safety and effectiveness of ibalizumab-uiyk (Trogarzo™) have not been established in pediatric individuals.

Description

CD4+ T-Cells are a type of white blood cell that scouts the body for foreign antigens; once it discovers a foreign antigen, it causes an immune response to fight them off. The HIV-1 virus attaches to CD4 receptors, enters the cells, and transmits the virus.

In the treatment of HIV-1, anti-retroviral (ART) regimens are employed to reduce the viral load (plasma HIV RNA) level to the lowest levels, or even undetectable levels, in order to increase survival rates, reduce the potential transmission of the disease to others, and prevent drug resistance. ART regimens are usually comprised of 2-3 drugs with at least two different mechanisms of action. Some examples of drug classes include nucleoside reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI), integrase strand transfer inhibitors (INSTI), or protease inhibitors (PI).

Drug regimens become less effective over time due to HIV-1 mutations (as part of the virus's survival technique), drug interactions, poor adherence to the drug regimens (due to regimen complexity or intolerance), and many other factors. Studies have shown that failing regimens with incomplete viral load suppression should not be fully discontinued; partially effective regimens should still be continued with the possibility of the addition of new therapy. Over time, individuals with multi-drug resistance will change drugs and drug classes in order to decrease the viral load further; this is called primary resistance. NOTE: It has also been shown that multi-drug-resistant HIV-1 can be contracted by a person who doesn't have HIV (transmitted resistance), which complicates ART regimens even further.

On March 6, 2018, ibalizumab-uiyk (Trogarzo™) was approved by the US Food and Drug Administration (FDA) for the treatment of HIV-1 infection, in combination with other antiretroviral(s), in heavily treatment-experienced adults with multi-drug-resistant HIV-1 infection failing their current antiretroviral regimen. Ibalizumab-uiyk (Trogarzo™) is administered every two weeks as an intravenous infusion over at least 15-30 minutes.

Ibalizumab-uiyk (Trogarzo™), a recombinant humanized monoclonal antibody, is an HIV-1 antiretroviral drug. It binds to domain 2 of CD4 receptors to protect the cell. When HIV-1 attaches to the CD4 receptors, ibalizumab-uiyk (Trogarzo™) blocks HIV-1 from entering and infecting the CD4+ T cells.

PEER-REVIEWED LITERATURE
Summary

The safety and effectiveness of ibalizumab-uiyk (Trogarzo™) were studied in a Phase 3, single-arm, multicenter trial of 40 heavily treatment-experienced HIV-infected subjects with multi-drug-resistant HIV-1. Subjects had a viral load greater than 1,000 copies/mL and documented resistance to at least one antiretroviral medication from each of three classes of antiretroviral medications (NRTI, NNRTI, and PI) as measured by resistance testing. Subjects were required to be treated with antiretrovirals for at least 6 months and be failing or to have had recently failed (i.e., in the last 8 weeks) therapy. The three phases of treatment were as follows:
  • A Control period on Days 0-6 was designed as an observational period to establish baseline HIV viral load. Subjects either received no therapy (if discontinued within 8 weeks) or stayed on current failing therapy.
  • A Functional Monotherapy period was designed on Days 7-13. On Day 7, subjects received a 2,000 mg loading dose of ibalizumab-uiyk (Trogarzo™). Those who were taking their failing regimen continued to do so.
  • A Maintenance period was designed from Day 15 to Week 25. On Day 14, the viral load was assessed for the primary endpoint, and thereafter the background regimen was optimized to include at least one drug to which the subject’s virus was susceptible. On Day 21, subjects began a maintenance regimen of 800 mg of ibalizumab-uiyk (Trogarzo™) every two weeks through Week 25.

At baseline, median viral load and CD4+ T cell counts were 35,350 copies/mL and 73 cells/mm3, respectively. The subjects were heavily treatment-experienced: 53% of participants had been treated with 10 or more antiretroviral drugs prior to trial enrollment; 98% percent had been treated with NRTIs, 98% with PIs, 80% with NNRTIs, 78% with INSTIs, 30% with gp41 fusion inhibitors, and 20% with CCR5 co-receptor antagonists.

The results showed a statistically significant difference in the primary efficacy endpoint --- the proportion of subjects achieving a ≥ 0.5 log10 decrease in viral load from Days 7-13 (result was 83%), as compared to the those with the decrease on Days 0-6 (result was 3%.) Secondary endpoints at Week 25 resulted in 43% of subjects achieving a viral load of less than 50 HIV-1 RNA copies/mL, and 50% of subjects achieving a viral load less than 200 HIV-1 RNA copies/mL. There was also a mean increase of CD4+ T-cells by 44 cells/mm3 from baseline. Thirteen percent of subjects discontinued treatment due to adverse effects or death at completion. Two subjects experienced serious reactions including rash or immune reconstitution inflammatory syndrome.

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

Aberg JA, Gallant JE, Ghanem KG, Emmanuel P, Zingman BS, Horberg MA; Infectious Diseases Society of America. Primary care guidelines for the management of persons infected with HIV: 2013 update by the HIV medicine association of the Infectious Diseases Society of America. Clin Infect Dis. 2014;58(1):e1-34.

Aberg JA, Kaplan JE, Libman H, et al; HIV Medicine Association of the Infectious Diseases Society of America. Primary care guidelines for the management of persons infected with human immunodeficiency virus: 2009 update by the HIV medicine Association of the Infectious Diseases Society of America. Clin Infect Dis. 2009;49(5):651-81.

American Hospital Formulary Service (AHFS). Drug Information 2019. DRUG. [Lexicomp Online Web site]. 04/30/18. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed March 15, 2019.

Booth C. Transmitted resistance. In: Geretti AM, ed. Antiretroviral Resistance in Clinical Practice. London: Mediscript; 2006: Chapter 10. Available at: https://www.ncbi.nlm.nih.gov/books/NBK2242/ . Accessed March 15, 2019.

Daar ES. Selecting an antiretroviral regimen for treatment-experienced HIV-infected patients who are failing therapy. [UpToDate Web Site]. 06/12/18. Available at: https://www.uptodate.com/contents/selecting-an-antiretroviral-regimen-for-treatment-experienced-hiv-infected-patients-who-are-failing-therapy?search=multidrug%20resistant%20HIV&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1 [via subscription only]. Accessed March 15, 2019.

Elsevier’s Clinical Pharmacology Compendium. Trogarzo. 12/18/18. [Clinical Key Web site]. Available at: https://www.clinicalkey.com/pharmacology/ [via subscription only]. Accessed March 15, 2019.

Emu B, Fessel J, Schrader S, et al. Phase 3 Study of Ibalizumab for Multidrug-Resistant HIV-1. N Engl J Med. 2018;379(7):645-654.

Lexi-Drugs Compendium. Trogarzo. 01/24/19. [Lexicomp Online Web site]. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed March 15, 2019.

Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV. Department of Health and Human Services. 10/25/18. Available at: https://aidsinfo.nih.gov/contentfiles/lvguidelines/adultandadolescentgl.pdf or https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv/15/virologic-failure . Accessed March 15, 2019.

Truven Health Analytics. Micromedex® DrugDex® Compendium. Trogarzo. 11/06/18. Greenwood Village, CO. [Micromedex® Solutions Web site]. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed March 15, 2019.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. ibalizumab-uiyk (Trogarzo) prescribing information and approval letter [FDA Web site]. 05/30/2018. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/ . Accessed March 15, 2019.



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)

B20 Human immunodeficiency virus [HIV] disease

Z16.33 Resistance to antiviral drug(s)



HCPCS Level II Code Number(s)

J1746 Injection, ibalizumab-uiyk, 10 mg


Revenue Code Number(s)

N/A

Coding and Billing Requirements


Cross References




Policy History

Revisions from MA08.096a
04/22/2020This policy has been reissued in accordance with the Company's annual review process.
04/10/2019The policy has been reviewed and reissued to communicate the Company’s continuing position on ibalizumab-uiyk (Trogarzo™).
01/01/2019This policy has been identified for the HCPCS code update, effective 01/01/2019.

The following HCPCS code has been added to this policy:
J1746 Injection, ibalizumab-uiyk, 10 mg

The following HCPCS codes have been termed from this policy:
C9399 Unclassified drugs or biologicals
J3590 Unclassified biologics

Revisions from MA08.096
07/02/2018This new policy has been issued to communicate the Company’s coverage position.






Version Effective Date: 01/01/2019
Version Issued Date: 01/03/2019
Version Reissued Date: 04/23/2020