Enfuvirtide (Fuzeon)

Summary

Enfuvirtide is an FDA approved twice daily peptide injection given under the skin (Fuzeon, approved March 2003) that blocks HIV-1 from fusing with, and so entering, CD4 cells (the immune cells HIV infects), reserved for treatment experienced patients whose virus is resistant to other drugs. In the two TORO phase 3 trials (1,005 people combined), adding enfuvirtide to an optimized regimen lowered HIV RNA (the amount of virus in the blood) by an extra 0.78 to 0.93 log10 copies per mL at 24 weeks, roughly a 6 to 8 fold larger drop, at the cost of injection site reactions in nearly every patient. It is rarely used today because newer oral and long acting drugs exist, but it remains a legitimate prescription antiretroviral (HIV medicine).

What is Enfuvirtide?

Enfuvirtide is an HIV-1 fusion inhibitor (synthetic 36 amino acid peptide mimicking the gp41 HR2 region). It is also known as Fuzeon, T-20, pentafuside, DP-178.

How does it work?

Enfuvirtide is a peptide copy of part of the HR2 region of the HIV-1 envelope glycoprotein gp41. It binds the HR1 region of gp41 during the conformational change that follows CD4 and coreceptor binding, blocking formation of the six-helix bundle that pulls the viral and cell membranes together. This stops the virus entering the cell. It has no activity against HIV-2 and is not affected by resistance to reverse transcriptase, protease, or integrase inhibitors.

FDA-approved uses of Enfuvirtide

Yes. Fuzeon was approved in March 2003 as the first HIV fusion inhibitor (a drug that stops the virus from entering cells). Its label covers HIV-1 infection in treatment experienced patients with evidence of HIV-1 replication (the virus still multiplying) despite ongoing antiretroviral therapy, always in combination with other antiretroviral (HIV) agents. Drugs@FDA, FDA's database of approved drugs, now lists the product's marketing status as discontinued, although the approval has not been withdrawn. [4] [6]

What does the evidence say about Enfuvirtide?

Two randomized open label phase 3 trials (TORO 1, n = 501, and TORO 2, n = 504) in heavily treatment experienced patients showed that enfuvirtide plus an optimized background regimen reduced HIV RNA by 1.70 and 1.43 log10 copies per mL at 24 weeks versus 0.76 and 0.65 with background alone. Pooled 48 week results confirmed durable benefit. Injection site reactions occurred in about 98% of patients and bacterial pneumonia was more frequent.

Human evidence

TORO 1 (North and South America, n = 501): mean change in HIV RNA at 24 weeks minus 1.696 log10 with enfuvirtide versus minus 0.764 log10 with optimized background alone (difference 0.93 log10); CD4 count rose 76 versus 32 cells per microliter. TORO 2 (Europe and Australia, n = 504): minus 1.43 versus minus 0.65 log10 (difference 0.78 log10). At 48 weeks in the pooled analysis, 30.4% of enfuvirtide patients had HIV RNA under 400 copies per mL versus 12.0% of controls. Injection site reactions occurred in 98% of enfuvirtide recipients and pneumonia in 4.7 versus 0.6 events per 100 patient years.

Animal evidence

Preclinical work characterized peptide inhibition of HIV-1 fusion in cell culture and pharmacokinetics in animals. Because HIV-1 does not infect standard laboratory animals, efficacy was established in humans rather than in animal disease models.

Key studies

Is Enfuvirtide legal in the United States?

FDA and compounding status

FDA approved prescription drug (Fuzeon, approved March 13, 2003, the first HIV fusion inhibitor). Drugs@FDA lists the Fuzeon product's marketing status as discontinued as of the last verified date; the approval itself has not been withdrawn. It is not on any 503A bulks list and is not a research chemical.

WADA status

Not WADA prohibited. Not named on the current prohibited list. Athletes should still confirm against the list in force for their season.

Regulatory timeline

1. Mar 13, 2003FDA

   FDA approves Fuzeon (enfuvirtide), the first HIV fusion inhibitor

   FDA approved enfuvirtide injection (Fuzeon), a 36-amino-acid peptide that blocks HIV-1 fusion with host cells, for treatment-experienced patients with HIV-1.

   Regulatory: FDA approvedSource: Drugs@FDA: Fuzeon (enfuvirtide) NDA 021481

Full tracker for Enfuvirtide or the category-wide tracker.

Enfuvirtide dose on the FDA label

Doses below are quoted from the FDA label for its approved uses, plus the doses used in the pivotal trials where noted. The prescriber sets the dose; PeptideAgent does not recommend doses or protocols.

FDA label (Fuzeon, 2019, via Drugs@FDA): adults, 90 mg (1 mL) injected subcutaneously twice daily into the upper arm, anterior thigh, or abdomen; pediatric patients weighing at least 11 kg, 2 mg/kg twice daily up to a maximum of 90 mg twice daily, with the dose adjusted as weight changes. It is always used in combination with other antiretroviral agents in treatment experienced patients with ongoing HIV-1 replication.

Routes reported

What are the side effects and interactions of Enfuvirtide?

Side effects

Interactions

Contraindications

How do people access Enfuvirtide legally?

Typical cost: List price is over 3,000 USD per month, making it one of the most expensive antiretrovirals. It is typically covered by insurance, Medicaid, or AIDS Drug Assistance Programs when a resistance profile justifies its use.

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Frequently asked questions

Decisions about starting, stopping, or combining any treatment belong with a licensed clinician who knows your history.

Sources

Numbered citations above point to these primary sources. PubMed entries link to the indexed abstract.