Clinical UM Guideline
|Guideline #:||CG-DRUG-20||Current Effective Date:||04/05/2016|
|Status:||Revised||Last Review Date:||02/04/2016|
This document addresses enfuvirtide (Fuzeon®) (Genetech, San Francisco, CA) which was approved by the U.S. Food and Drug Administration (FDA) as the first injectable agent in the treatment of human immunodeficiency virus (HIV) infection in adults and children older than 6 years of age who have ongoing viral replication despite ongoing antiretroviral therapy. Enfuvirtide is the first in a class of HIV drugs known as fusion inhibitors that interfere with the ability of the virus to enter the cell and is used in conjunction with other anti-retroviral agents.
Not Medically Necessary:
The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.
|J1324||Injection, enfuvirtide, 1 mg [Fuzeon]|
Enfuvirtide is an inhibitor of the fusion of HIV-1 with CD4+ cells. Enfuvirtide interferes with the entry of HIV-1 into cells by inhibiting fusion of viral and cellular membranes. The FDA approved enfuvirtide in 2003 in combination with other antiretroviral agents for the treatment of HIV-1 infection in treatment experienced individuals with HIV-1 replication despite ongoing antiretroviral therapy.
Two 24-week randomized, controlled, open-label studies (TORO-1 and TORO-2) included 955 individuals with HIV-infected treatment-experience consisting of 3 to 5 antiretroviral agents selected on the basis of the participants' prior treatment history and baseline genotypic and phenotypic viral resistance measurements. Subjects were randomized at a 2:1 ratio to subcutaneous enfuvirtide 90 mg given twice a day with background regimen or background regimen alone. Participants 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 individuals receiving therapy without enfuvirtide (Lalezari, 2003; Lazarrin, 2003; Nelson 2005; Trottier, 2005). The two phase III multicenter trials required subjects to have either:
In an optional 48-week extension study, Reynes (2007) and colleagues evaluated the long-term virologic and immunologic effects of enfuvirtide therapy. Viral load reduction of greater than or equal to 1.0 log10 from baseline was considered a response. Out of the original combined cohort of 955 individuals, 362 (55%) individuals in the enfuvirtide treatment group completed 96 weeks of the study. At 96 weeks, mean copies of viral load decreased from baseline -1.1 log10 for participants that switched from the control group to enfuvirtide plus optimized background (OB) antiretroviral therapy versus -2.1 log10 reduction in HIV-1-RNA copies for those in the treatment group. A viral load of less than 400 copies per millimeter was achieved for 26.5% of participants and 17.5% of the participants achieved less than 50 copies per millimeter. The investigators concluded safety and efficacy of enfuvirtide plus OB were durable in the 96-week study.
In a subset analysis of the TORO study, body composition and metabolic parameters were evaluated at 48 weeks in participants from the enfuvirtide treatment group compared to the OB group (Cooper, 2011). There were no significant differences between the groups for increases in total cholesterol, high-density lipoprotein (HDL) and glucose. There was a significant mean change of body weight from baseline +0.99 kg (95% confidence interval [CI] +0.54- + 1.44) for the treatment group but there was no significant change from baseline for the OB control group. There was a significant difference in the mean change from baseline waist circumference between treatment groups of 1.73 (95% CI 0.27- 3.20). The mean changes in other anthropometric measurements between cohorts were not significantly different. The authors concluded regimens with enfuvirtide did not have an adverse effect on body composition and metabolic parameters when compared to OB antiretroviral regimens.
A 2-year safety and tolerability study of enfuvirtide as salvage therapy was conducted in 23 Thai individuals with HIV-1 disease. A total of 96 weeks of treatment was completed by 74% (17) participants. Of the 17 participants, 6 withdrew prior to completion of the study, with 2 consents withdrawn, 1 adverse event reported, and 3 deaths from HIV related complications. Local injection site reactions were the most common adverse event and good control of the HIV disease was reported.
According to the product information label (2015), there are no studies of enfuvirtide in antiretroviral-naïve subjects. Additionally, there was insufficient data to establish recommended dosing for the pediatric population below 6 years of age.
Adverse Events and Warnings
Warnings and precautions from the FDA Product Information Label (2015) include the following:
The most common adverse reactions are local injection site reactions, diarrhea, nausea, and fatigue. In a randomized study by Lalezari (2008), the local injection site reactions were significantly reduced with the use of needle-free injection devices.
The updated U.S. Public Health Service guideline for the management of occupational exposure and postexposure prophylaxis (PEP) (Kuhar, 2013) states enfuvirtide:
…is not generally recommended as PEP, unless its use is deemed necessary during expert consultation due to its subcutaneous route of administration, significant side effects, and potential for development of anti-T20 antibodies that may cause false-positive HIV antibody tests among uninfected patients.
Enfuvirtide is listed in the guideline as an alternative agent for use as PEP only with expert consultation.
The American Hospital Formulary Service (2015) states:
Enfuvirtide is used in conjunction with other antiretrovirals for postexposure prophylaxis of HIV infection following occupational exposure (PEP) in health-care personnel and other individuals exposed via percutaneous injury (e.g., needlestick, cut with sharp object) or mucous membrane or nonintact skin (e.g., chapped, abraded, dermatitis) contact with blood, tissue, or other body fluids that might contain HIV.
There are ongoing clinical trials studying enfuvirtide as a component of multidrug regimens for initial treatment of HIV infection, but the results of the pivotal trial need to be validated. Additional clinical trials are investigating the various combinations of anti-HIV drugs to determine the optimal combination and timing.
Peer Reviewed Publications:
Government Agency, Medical Society, and Other Authoritative Publications:
|Websites for Additional Information|
The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.
|Revised||02/04/2016||Medical Policy & Technology Assessment Committee (MPTAC) review. Reformatted criteria. Expanded Medically Necessary criteria to include intolerance to ART therapy. Updated Description, Discussion, and References sections. Removed ICD-9 codes from Coding section.|
|Reviewed||02/05/2015||MPTAC review. Updated Description, Discussion, and References sections.|
|Reviewed||02/13/2014||MPTAC review. Updated Description/Scope, Discussion, References section. Added Websites section.|
|Reviewed||02/14/2013||MPTAC review. Updated Discussion, References sections.|
|Reviewed||02/16/2012||MPTAC review. Updated Discussion, References sections.|
|Reviewed||02/17/2011||MPTAC review. Updated Discussion, References sections.|
|Reviewed||05/13/2010||MPTAC review. Updated Coding, References sections.|
|Revised||05/21/2009||MPTAC review. Added medical necessity criteria for occupational postexposure prophylaxis. Added clarifying not medically necessary criteria. Rationale, references, websites and coding updated.|
|New||05/17/2007||MPTAC review. Initial guideline development.|