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Clinical Policy Bulletin:
Enfuvirtide (Fuzeon)
Number: 0671


Policy

  1. Aetna considers enfuvirtide (Fuzeon) injection medically necessary for HIV-infected persons over the age of 6 years who meet either of the following medical necessity criteria:

    1. Viremia despite 3 or more prior months of therapy with a nucleoside/nucleotide reverse transcriptase inhibitor (NRTI), non-nucleoside reverse transcriptase inhibitor (NNRTI), and a protease inhibitor (PI) (see Appendix); or
    2. Viremia and documented resistance or intolerance to at least 1 member in each of the NRTI, NNRTI and PI classes.
       
  2. Aetna considers enfuvirtide experimental and investigational for treatment-naive HIV-infected persons and for all other indications because its effectiveness for indications other than the ones listed above has not been established.



Background

Enfuvirtide (Fuzeon) injection (Hoffman-La Roche Inc., Nutley, NJ and Trimeris, Inc., Durham, NC) was approved by the Food and Drug Administration for the combination treatment of human immunodeficiency virus (HIV) infection in adults and children (older than 6 years of age) who have ongoing viral replication despite ongoing anti-retroviral therapy.  Enfuvirtide is the first in a new class of HIV drugs known as fusion inhibitors.

Two 24-week randomized, controlled open-label studies (TORO-1 and TORO-2) of 955 HIV-infected treatment-experienced patients showed that patients receiving enfuvirtide as a part of a combination of anti-HIV drugs experienced greater immunologic improvements and were twice as likely to achieve undetectable plasma levels of HIV compared to patients receiving therapy without enfuvirtide (Lalezari et al, 2003; Lazzarin et al, 2003).

Enfuvirtide is administered as a twice-daily subcutaneous injection.  The recommended adult dose is 90 mg twice-daily; the dosage for children (at least 6 years old) is 2 mg/kg twice-daily.

Injection site reactions with pain, erythema, induration, nodules and cysts occurred in 98 % of patients receiving enfuvirtide, but led to discontinuation of the drug in only 3 %.  Other events most frequently reported in subjects receiving enfuvirtide were diarrhea, nausea, and fatigue.  Less common adverse events include headache, peripheral neuropathy, dizziness, insomnia, depression, decreased appetite, asthenia, myalgia, constipation and pancreatitis.  The product labeling states that physicians should monitor patients for signs and symptoms of pneumonia.  Although bacterial pneumonia was uncommon in clinical trials, more patients treated with enfuvirtide developed bacterial pneumonia than did patients who did not receive enfuvirtide.

The Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission’s recommendations for use of anti-retroviral drugs in pregnant HIV-1-infected women (2012) stated that “Safety and PK [pharmacokinetic] data in pregnancy are insufficient to recommend use of the entry inhibitors enfuvirtide and maraviroc in ARV-naïve women during pregnancy.  Use of these agents can be considered for women who have failed therapy with several other classes of ARV drugs after consultation with HIV and obstetric specialists”.  Furthermore, the Panel on Antiretroviral Therapy and Medical Management of HIV-Infected Children’s guidelines on “The use of anti-retroviral agents in pediatric HIV infection” (2012) stated that “Currently, data are insufficient to recommend use of enfuvirtide for initial therapy of children”.

Appendix

Table: Pharmaceuticals for HIV and AIDS

Protease Inhibitors (PIs)
Generic name Brand Name Abbreviation Manufacturer
Saquinavir Invirase SQV (HGC) Roche
Saquinavir Fortovase SQV (SGC) Roche
Ritonavir Norvir RTV Abbott
Indinavir Crixivan IDV Merck
Nelfinavir Viracept NFV Pfizer
Amprenavir Agenerase APV GSK
Lopinavir + ritonavir Kaletra LPV Abbott
Atazanavir Reyataz ATZ BMS
       
Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs)
Generic name Brand Name Abbreviation Manufacturer
Zidovudine Retrovir AZT or ZDV GSK
Lamivudine Epivir 3TC GSK
Zidovudine + lamivudine Combivir AZT + 3TC GSK
ABC + AZT = 3TC Trizivir ABC+AZT+3TC GSK
Abacavir Ziagen ABC GSK
Zalcitabine Hivid ddC Roche
Didanosine (bv) Videx ddI BMS
Didanosine (drc) Videx EC ddI BMS
Stavudine Zerit d4T BMS
Emtricitabine Emtriva FTC Gilead
Tenofovir disoproxil fumarate Viread TDF or Bis(POC) PMPA Gilead
       
Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
Generic name Brand Name Abbreviation Manufacturer
Nevirapine Viramune NVP Boehringer
Delavirdine Rescriptor DLV Pfizer
Efavirenz Sustiva EFV BMS
       
Adapted from AIDSMeds.com; 2003.
Key: GSK = GlaxoSmithKline; BMS = Bristol-Myers Squibb; HGC = hard gel cap; SGC = soft gel cap; bv = buffered versions; drc = delayed-release capsules.
 
CPT Codes / HCPCS Codes / ICD-9 Codes
HCPCS codes covered if selection criteria are met:
J1324 Injection, enfuvirtide, 1 mg
ICD-9 codes covered if selection criteria are met:
042 Human immunodeficiency virus [HIV] disease
Other ICD-9 codes related to the CPB:
790.8 Viremia, unspecified


The above policy is based on the following references:
  1. No authors listed. Enfuvirtide (Fuzeon) for HIV infection. Med Lett Drugs Ther. 2003;45(1159):49-50.
  2. Tashima KT, Carpenter CC. Fusion inhibition--a major but costly step forward in the treatment of HIV-1. N Engl J Med. 2003;348(22):2249-22450.
  3. Kilby JM, Eron JJ. Novel therapies based on mechanisms of HIV-1 cell entry. N Engl J Med. 2003;348(22):2228-2238.
  4. Lazzarin A, Clotet B, Cooper D, et al., and the TORO 2 Study Group. Efficacy of enfuvirtide in patients infected with drug-resistant HIV-1 in Europe and Australia. N Engl J Med. 2003;348(22):2186-2195.
  5. Steinbrook R. HIV infection--a new drug and new costs. N Engl J Med. 2003;348(22):2171-2172.
  6. Lalezari JP, Henry K, O'Hearn M, et al., and the TORO 1 Study Group. Enfuvirtide, an HIV-1 fusion inhibitor, for drug-resistant HIV infection in North and South America. N Engl J Med. 2003;348(22):2175-2185.
  7. Roche Pharmaceuticals and Trimeris, Inc. Fuzeon (enfuvirtide) for injection. Complete Product Information. No. 27898287. Nutley, NJ: Roche Laboratories, Inc.; March 2003.
  8. AIDSMeds.com. Drugs for HIV and AIDS. Brooklyn, NY: AIDSMeds.com; April 22, 2003. Available at: http://www.aidsmeds.com/List.htm. Accessed: August 8, 2003.
  9. Lalezari JP, DeJesus E, Northfelt DW, et al. A controlled Phase II trial assessing three doses of enfuvirtide (T-20) in combination with abacavir, amprenavir, ritonavir and efavirenz in non-nucleoside reverse transcriptase inhibitor-naive HIV-infected adults. Antivir Ther. 2003;8(4):279-287.
  10. Hardy H, Skolnik PR. Enfuvirtide, a new fusion inhibitor for therapy of human immunodeficiency virus infection. Pharmacotherapy. 2004;24(2):198-211.
  11. Clotet B, Raffi F, Cooper D, et al. Clinical management of treatment-experienced, HIV-infected patients with the fusion inhibitor enfuvirtide: Consensus recommendations. AIDS. 2004;18(8):1137-1146.
  12. Canadian Coordinating Office for Health Technology Assessment (CCOHTA). Enfuvirtide, a new treatment for HIV infection. Issues in Emerging Health Technologies Issue 50. Ottawa, ON: CCOHTA; 2003.
  13. Sax PE, Losina E, Weinstein MC, et al. Cost-effectiveness of enfuvirtide in treatment-experienced patients with advanced HIV disease. J Acquir Immune Defic Syndr. 2005;39(1):69-77.
  14. Montaner J, Guimaraes D, Chung J, et al. Prognostic staging of extensively pretreated patients with advanced HIV-1 disease. HIV Clin Trials. 2005;6(6):281-290.
  15. Nelson M, Arasteh K, Clotet B, et al. Durable efficacy of enfuvirtide over 48 weeks in heavily treatment-experienced HIV-1-infected patients in the T-20 versus optimized background regimen only 1 and 2 clinical trials. J Acquir Immune Defic Syndr. 2005;40(4):404-412.
  16. Dwyer DE, Workman C, Hales G, et al. Enfuvirtide in HIV-1-infected individuals changing therapy to a nucleoside reverse transcriptase inhibitor sparing regimen: The ALLIANCE Study. Antivir Ther. 2006;11(4):409-419.
  17. Youle M, Staszweski S, Clotet B, et al. Concomitant use of an active boosted protease inhibitor with enfuvirtide in treatment-experienced, HIV-infected individuals: Recent data and consensus recommendations. HIV Clin Trials. 2006;7(2):86-96.
  18. Salzberger B, Daumer M, Gute P, et al. Consensus recommendation from a group of German experts for the use of enfuvirtide in heavily pretreated HIV patients. Eur J Med Res. 2007;12(3):93-102.
  19. Ruof J, Dusek A, DeSpirito M, Demasi RA. Cost-efficacy comparison among three antiretroviral regimens in HIV-1 infected, treatment-experienced patients. Clin Drug Investig. 2007;27(7):469-479.
  20. Wright D, Rodriguez A, Godofsky E, et al. Efficacy and safety of 48 weeks of enfuvirtide 180 mg once-daily dosing versus 90 mg twice-daily dosing in HIV-infected patients. HIV Clin Trials. 2008;9(2):73-82.
  21. Pulido F, Del Pozo MA, Fernández-Guerrero M, et al; ESPPE Study Group. Patients' perception and effectiveness of a treatment containing enfuvirtide when used in HIV-infected patients without very advanced disease. HIV Clin Trials. 2008;9(2):83-90.
  22. Streinu-Cercel A, de Gorgolas M, Müller M, et al. Switching from a toxicity-causing antiretroviral to enfuvirtide in patients with HIV: The SWITCH TOX study. HIV Clin Trials. 2008;9(6):375-386.
  23. Clotet B, Capetti A, Soto-Ramirez LE, et al. A randomized, controlled study evaluating an induction treatment strategy in which enfuvirtide was added to an oral, highly active antiretroviral therapy regimen in treatment-experienced patients: The INTENSE study. J Antimicrob Chemother. 2008;62(6):1374-1378.
  24. Makinson A, Reynes J. The fusion inhibitor enfuvirtide in recent antiretroviral strategies. Curr Opin HIV AIDS. 2009;4(2):150-158.
  25. Viard JP, Fagard C, Chaix ML, et al; ANRS 123 ETOILE trial group. Immunological success is predicted by enfuvirtide but not interleukin-2 therapy in immunodepressed patients. AIDS. 2009;23(11):1383-1388.
  26. Teicher E, Abbara C, Duclos-Vallée JC, et al. Enfuvirtide: A safe and effective antiretroviral agent for human immunodeficiency virus-infected patients shortly after liver transplantation. Liver Transpl. 2009;15(10):1336-1342.
  27. Cooper DA, Cordery DV, Reiss P, et al; TORO 1 and TORO 2 Study Groups. The effects of enfuvirtide therapy on body composition and metabolic parameters over 48 weeks in the TORO body imaging substudy. HIV Med. 2011;12(1):31-39.
  28. Prasithsirikul W, Hanvanich M, Suwanagool S, et al. Two-year safety and tolerability study of enfuvertide use in salvage therapy of Thai HIV-1 experienced cases. J Med Assoc Thai. 2011;94(3):303-308.
  29. Pichenot M, Deuffic-Burban S, Cuzin L, Yazdanpanah Y. Efficacy of new antiretroviral drugs in treatment-experienced HIV-infected patients: A systematic review and meta-analysis of recent randomized controlled trials. HIV Med. 2012;13(3):148-155.
  30. Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission. Recommendations for use of antiretroviral drugs in pregnant HIV-1-infected women for maternal health and interventions to reduce perinatal HIV transmission in the United States. Rockville (MD): Public Health Service Task Force; July 31, 2012. Available at: http://www.guideline.gov/content.aspx?id=38253&search=enfuvirtide. Accessed July 23, 2013.
  31. Panel on Antiretroviral Therapy and Medical Management of HIV-Infected Children. Guidelines for the use of antiretroviral agents in pediatric HIV infection. Bethesda (MD): U.S. Department of Health and Human Services (DHHS); November 5, 2012. Available at: http://www.guideline.gov/content.aspx?id=38702&search=enfuvirtide. Accessed July 24, 2013.


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Copyright Aetna Inc. All rights reserved. Clinical Policy Bulletins are developed by Aetna to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. This Clinical Policy Bulletin contains only a partial, general description of plan or program benefits and does not constitute a contract. Aetna does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Aetna or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. This Clinical Policy Bulletin may be updated and therefore is subject to change.
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