The purpose of this policy is to provide general information applicable to the administration of health benefits that Horizon Blue Cross Blue Shield of New Jersey and Horizon Healthcare of New Jersey, Inc. (collectively “Horizon BCBSNJ”) insures or administers. If the member’s contract benefits differ from the medical policy, the contract prevails. Although a service, supply or procedure may be medically necessary, it may be subject to limitations and/or exclusions under a member’s benefit plan. If a service, supply or procedure is not covered and the member proceeds to obtain the service, supply or procedure, the member may be responsible for the cost. Decisions regarding treatment and treatment plans are the responsibility of the physician. This policy is not intended to direct the course of clinical care a physician provides to a member, and it does not replace a physician’s independent professional clinical judgment or duty to exercise special knowledge and skill in the treatment of Horizon BCBSNJ members. Horizon BCBSNJ is not responsible for, does not provide, and does not hold itself out as a provider of medical care. The physician remains responsible for the quality and type of health care services provided to a Horizon BCBSNJ member.
Horizon BCBSNJ medical policies do not constitute medical advice, authorization, certification, approval, explanation of benefits, offer of coverage, contract or guarantee of payment.
Approximately 1.2 million Americans have HIV-1 infection. Up to 25,000 Americans with HIV-1 infection are considered multi-drug resistant (MDR), with approximately 12,000 of these patients failing their current antiretroviral regimen.
Ibalizumab-uiyk (Trogarzo) is a novel biologic HIV-1 antiretroviral drug. It is indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in heavily treatment-experienced adults with multidrug resistant HIV-1 infection failing their current antiretroviral regimen. Ibalizumab-uiyk (Trogarzo) is reserved for treatment-experienced people living with HIV, and it is a CD4-directed post-attachment HIV-1 inhibitor. Ibalizumab-uiyk, a recombinant humanized monoclonal antibody, blocks HIV-1 from infecting CD4+ T cells by binding to domain 2 of CD4 and interfering with post-attachment steps required for the entry of HIV-1 virus particles into host cells and preventing the viral transmission that occurs via cell-cell fusion. Trogarzo was approved under orphan drug designation as well as fast track, priority review, and breakthrough therapy designations.
The FDA approval of Trogarzo was based on a single arm, multicenter clinical trial conducted in 40 heavily treatment-experienced HIV-infected patients with multidrug resistant HIV-1. Patients were required to have 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. Patients must have been treated with antiretrovirals for at least 6 months and be failing or had recently failed (i.e., in the last 8 weeks) therapy. The primary endpoint was to demonstrate the antiviral activity of ibalizumab 7 days after the first dose of ibalizumab. Patients receiving their current failing ART regimens were monitored during a 7-day control period. Thereafter, a loading dose of 2,000 mg of intravenous ibalizumab was added to their regimen. As the primary efficacy endpoint, 83% patients achieved ≥ 0.5 log10 decrease in viral load 7 days after initiating Ibalizumab therapy (95% CI: 67%, 93%), which was day 14 of the study. Ibalizumab was continued at doses of 800 mg IV every two weeks after 24 weeks. At Week 25, viral load <50 and <200 HIV-1 RNA copies/mL was achieved in 43% and 50% of subjects, respectively. Furthermore, at Week 25, 55% of patients had a ≥ 1 log10 reduction in viral load, and 48% of patients had a ≥ 2 log10 reduction in viral load. The most common adverse reactions were diarrhea, dizziness, nausea, and rash.
(Note: For Medicare Advantage, please refer to the Medicare Coverage Section below for coverage guidance.)
I. Ibalizumab-uiyk (Trogarzo) is therapy is medically necessary based on the FDA-approved indication for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in heavily treatment-experienced adults with multidrug resistant HIV-1 infection failing their current antiretroviral regimen:
· Member is ≥18 years of age
· Member has documented RNA viral load >1,000 copies/mL
· Member has 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
· Member has a history of at least 6 months on antiretroviral treatment
· Member will be using ibalizumab-uiyk (Trogarzo) in combination with antiretroviral treatment drugs.
· Nucleoside Reverse Transcriptase Inhibitors (NRTIs) include: Emtriva® (emtricitabine), Epivir® (3TC, lamivudine), Retrovir® (AZT, zidovudine), Videx-EC® (ddI, didanosine), Viread® (tenofovir DF), Zerit® (d4T, stavudine), and Ziagen® (abacavir). Several of the NRTI drugs may be combined into one tablet to make it easier to take your medications. These drugs are known as fixed-dose combinations: Combivir® (zidovoudine + lamivudine), Descovy® (tenofovir alafenamide + emtricitabine), Epzicom® (lamivudine+ abacavir), Trizivir® (zidovudine+ lamivudine+ abacavir), and Truvada® (tenofovir DF+ emtricitabine)
· Non-nucleoside reverse transcriptase inhibitors (NNRTIs) include: Edurant® (rilpivirine), Intelence® (etravirine), Rescriptor® (delavirdine), Sustiva® (efavirenz), and Viramune® (nevirapine).
· Protease Inhibitors (PIs) include: Aptivus® (tipranavir), Crixivan® (indinavir), Invirase® (saquinavir), Kaletra® (lopinavir + ritonavir), Lexiva® (fosamprenavir), Norvir® (ritonavir), Prezista®(darunavir), Reyataz® (atazanavir), and Viracept® (nelfinavir).]
· Multi-class drug combinations include drugs from two different groups in a complete HIV drug regimen, which are the following: Atripla® (efavirenz + emtricitabine + tenofovir DF), Complera® (rilpivirine + emtricitabine + tenofovir DF), Genvoya® (elvitegravir + cobicistat + emtricitabine + tenofovir alafenamide), Odefsey® (rilpivirine + emtricitabine + tenofovir alafenamide), Stribild® (elvitegravir + cobicistat + emtricitabine + tenofovir DF), Triumeq® (dolutegravir + lamivudine + abacavir)
· Guidelines for the use of Antiretroviral agents in HIV-1-infected adults and adolescents from the Department of Health & Human Services (DHHS) have been updated to incorporate Trogarzo (ibalizumab-uiyk). In the management of treatment experienced patients with virologic failure the DHHS guidelines state patients with ongoing detectable viremia who lack sufficient treatment options to construct a fully suppressive regimen may be candidates for the CD4 post-attachment inhibitor ibalizumab. ]
II. When ibalizumab-uiyk (Trogarzo) is considered medically necessary, initial therapy will be approved for 6 months based on FDA-approved labeling:
III. Continued therapy with ibalizumab-uiyk (Trogarzo) will be considered every 6 months if the following criteria are met:
· Administer intravenously as a single loading dose of 2,000 mg followed by a maintenance dose of 800 mg every 2 weeks after dilution in 250 mL of 0.9% sodium chloride injection
· If an 800 mg maintenance dose was missed by 3 or more days, another 2,000 mg loading dose should be administered, instead of an 800 mg dose
· Decreased viral load indicating clinically significant disease response and improvement to achieve <200 copies/mL
· Absence of resistance or unacceptable toxicity from the requested drug (e.g. immune reconstitution inflammatory syndrome (IRIS))
[INFORMATIONAL NOTE: Patients with an immune reconstitution inflammatory syndrome (IRIS) may develop symptoms within one week to a few months after the initiation of antiretroviral therapy (ART). Immune reconstitution inflammatory syndrome (IRIS) can have various manifestations, including lymph node inflammation associated with Mycobacterium avium intracellulare (MAI), eye inflammation (uveitis or vitritis) associated with cytomegalovirus (CMV), worsening of tuberculosis, cryptococcosis, or toxoplasmosis symptoms, and elevated liver enzymes in people with hepatitis B or C co-infection. There have also been case reports of temporary worsening of Pneumocystis pneumonia (PCP), progressive multifocal lymphadenopathy (PML), herpes simplex and varicella zoster (shingles), warts due to human papillomavirus (HPV) and other skin conditions.]
III. All other uses of ibalizumab-uiyk (Trogarzo) are considered investigational.
There is no National Coverage Determination (NCD) or Local Coverage Determination (LCD) for jurisdiction JL for this service. Therefore, Medicare Advantage Products will follow the Horizon BCBSNJ medical policy.
Horizon BCBSNJ Medical Policy Development Process:
This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.
HIV-1, Ibalizumab-uiyk (Trogarzo) for
1. Trogarzo (ibalizumab-uiyk) [Prescribing Information]. TalMed Biologics. Irvine, CA. 3/2018.
2. U.S. Food and Drug Administration: News Release. FDA approves new HIV treatment for patients who have limited treatment options. March 6, 2018. Available: https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm599657.htm. Accessed March 2018.
3. ClinicalTrials.gov. Ibalizumab Plus Optimized Background Regimen in Patient With Multi-Drug Resistant HIV . Available at: https://clinicaltrials.gov/ct2/show/NCT02475629?term=TMB-301&rank=1. Accessed March 2018.
4. FDA Center Watch. Trogarzo (ibalizumab-uiyk). Available: https://www.centerwatch.com/drug-information/fda-approved-drugs/drug/100252/trogarzo-ibalizumab-uiyk. Accessed March 2018.
5. "Virologic Failure Management Of The Treatment-Experienced Patient Adult And Adolescent ARV". Aidsinfo, 2018, https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv/15/virologic-failure. Accessed 6 Dec 2018.
(The list of codes is not intended to be all-inclusive and is included below for informational purposes only. Inclusion or exclusion of a procedure, diagnosis, drug or device code(s) does not constitute or imply authorization, certification, approval, offer of coverage or guarantee of payment.)
* CPT only copyright 2018 American Medical Association. All rights reserved. CPT is a registered trademark of the American Medical Association.
Medical policies can be highly technical and are designed for use by the Horizon BCBSNJ professional staff in making coverage determinations. Members referring to this policy should discuss it with their treating physician, and should refer to their specific benefit plan for the terms, conditions, limitations and exclusions of their coverage.
The Horizon BCBSNJ Medical Policy Manual is proprietary. It is to be used only as authorized by Horizon BCBSNJ and its affiliates. The contents of this Medical Policy are not to be copied, reproduced or circulated to other parties without the express written consent of Horizon BCBSNJ. The contents of this Medical Policy may be updated or changed without notice, unless otherwise required by law and/or regulation. However, benefit determinations are made in the context of medical policies existing at the time of the decision and are not subject to later revision as the result of a change in medical policy