HEALTH-SYSTEM EDITION

P & T PORTFOLIO

Generic name

Enfuvirtide for injection

Proprietary name/manufacturer

Fuzeon/Roche, Trimeris

FDA-approved Indication

Approved for use in combination with other antiretroviral agents for the treatment of HIV-1 infection in treatment-experienced patients with evidence of HIV-1 replication despite ongoing antiretroviral therapy

Pharmacology

Enfuvirtide is a linear 36-amino acid synthetic peptide that interferes with the entry of HIV-1 into cells by inhibiting fusion of viral and cellular membranes, which prevents the conformational changes required for the fusion of viral and cellular membranes by binding to the first heptad-repeat (HR1) in the gp41 subunit of the viral envelope glycoprotein. Enfuvirtide appears to exhibit additive to synergistic effects in cell culture assays when combined with individual members of various other antiretroviral classes.

The accelerated FDA approval of enfuvirtide was based upon data from two ongoing 24-week multinational clinical trials involving approximately 1,000 treatment-experienced adult patients with HIV-1 infection. Study results demonstrated that patients receiving enfuvirtide as part of an optimized background regimen experienced greater immunologic improvements based upon CD4 cell counts and were twice as likely to achieve undetectable plasma levels of HIV compared with patients receiving an individualized regimen alone. In addition, patients with two or more active drugs in their background regimen were more likely to achieve undetectable levels of HIV.

However, there are no results from controlled clinical trials evaluating the effect of enfuvirtide on clinical progression of HIV-1 or in antiretroviral-naive patients. In addition, HIV-1 isolates with reduced susceptibility to enfuvirtide have been recovered from subjects treated with enfuvirtide in combination with other antiretrovirals during clinical trials. Only limited efficacy data are available in pediatric patients six years of age and older.

Warnings

• An increased rate of bacterial pneumonia was seen in subjects treated with enfuvirtide during clinical trials.

• Hypersensitivity reactions have been associated with enfuvirtide and may recur on rechallenge.

Adverse effects

The most common adverse effects with enfuvirtide included injection-site reactions (98%), diarrhea (26.8%), nausea (20.1%), fatigue (16.1%), and insomnia (11.3%).

Less common adverse effects included peripheral neuropathy (8.9%), depression (8.6%), cough (7.4%), decreased weight (6.5%), decreased appetite (6.3%), sinusitis (6.2%), anxiety (5.7%), and asthenia (5.7%).

Pharmacokinetics

Cost (AWP)*

Cost per 90-mg vial, $33.32; cost per year, $23,988

*AWP may not accurately represent the actual pharmacy cost because wide contractual variations exist among institutions.

Conclusion/comments

Enfuvirtide is a HIV-1 fusion inhibitor that has demonstrated efficacy when used in combination with other antiretrovirals for the treatment of HIV-1 infection in treatment-experienced patients with evidence of HIV-1 replication despite ongoing antiretroviral therapy. It is the first of a new class of agents that work by preventing the HIV virus from invading white blood cells, unlike other classes of HIV drugs that work after the HIV has entered the human immune cell and begun its replication process.

Unfortunately, it appears that the demand for enfuvirtide will exceed the amount of the drug produced in 2003 and possibly longer. In view of its limited supply, enfuvirtide distribution will be handled by a single mail-service pharmacy—Progressive Distribution Program, (866) 694-6670—for the first year or so of marketing. The drug's manufacturers have set up a program through which physicians can obtain enfuvirtide for individual patients on a first-come, first-served basis without having their treatment interrupted due to supply problems.

Published July 2003. Content based on medical literature and product information available at that time.

P&T Portfolio: Fuzeon. Drug Topics Jul. 21, 2003;147:HSE30.