Clinical UM Guideline
|Guideline #:||CG-DRUG-20||Current Effective Date:||04/16/2013|
|Status:||Reviewed||Last Review Date:||02/14/2013|
Enfuvirtide (Fuzeon) (Hoffman-La Roche Inc., Nutley, NJ and Trimeris, Inc., Durham, NC) was approved by the U.S. Food and Drug Administration (FDA) for use in conjunction with other anti-retroviral agents in the treatment of human immunodeficiency virus (HIV) infection in adults and children older than 6 years old 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.
Enfuvirtide is considered medically necessary when all of the following criteria are met:
*Failure is defined as a confirmed HIV RNA level of greater than 50 copies/mL while on therapy.
Enfuvirtide is considered medically necessary for postexposure prophylaxis of HIV infection in healthcare workers and other individuals exposed occupationally via percutaneous injury or mucous membrane or nonintact skin contact with blood, tissues, or other body fluids associated with a risk for transmission of the HIV virus.
Not Medically Necessary:
Enfuvirtide is considered not medically necessary when the criteria above are not met.
Enfuvirtide is considered not medically necessary for all other applications.
The following codes for treatments and procedures applicable to this document are included below for informational purposes. A draft of future ICD-10 Coding (effective 10/01/2014) related to this document, as it might look today, is included below for your reference. 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]|
|ICD-10 Diagnosis||ICD-10-CM draft codes; effective 10/01/2014:|
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. Enfuvirtide binds to the first heptad-repeat (HR1) in the glycoprotein 41 (gp41) subunit of the viral envelope glycoprotein and prevents the conformational changes required for the 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 3 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% 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 two-year safety and tolerability study of enfuvirtide as salvage therapy was conducted in twenty-three Thai individuals with HIV-1 disease. Ninety-six weeks of treatment was completed by 74% (17) participants. Six participants withdrew prior to completion of the study, with two consents withdrawn, one adverse event reported, and three 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 (2012), 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 (2012) 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 U.S. Public Health Service guideline for the management of occupational exposure and postexposure prophylaxis (PEP) (Center for Disease Control and Prevention [CDC], 2005) states enfuvirtide has theoretic benefits for use in PEP, since its activity occurs before the virus enters the cell. Enfuvirtide may be considered an alternative to expanded PEP regimens (CDC, 2005). However, it is not routinely recommended for this use in part due to the inconvenience of the subcutaneous administration and the availability of other regimens.
The American Hospital Formulary Service (2012) states:
Enfuvirtide is recommended as an alternative agent for use in conjunction with other antiretroviral agents for postexposure prophylaxis of HIV infection in health-care workers and other individuals exposed occupationally via percutaneous injury or mucous membrane or nonintact skin contact with blood, tissues, or other body fluids associated with a risk for transmission of the virus. Although enfuvirtide is not recommended for routine postexposure prophylaxis following occupational exposure to HIV because the drug is administered subcutaneously, some experts suggest that enfuvirtide can be considered for use in expanded regimens with expert consultation.
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:
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.
|Reviewed||02/14/2013||Medical Policy & Technology Assessment Committee (MPTAC) review. Updated Discussion, References and Websites sections.|
|Reviewed||02/16/2012||MPTAC review. Updated Discussion, References and Websites sections.|
|Reviewed||02/17/2011||MPTAC review. Updated Discussion, References and Websites sections.|
|Reviewed||05/13/2010||MPTAC review. Updated Coding, References and Websites 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.|