Evidence memo / Immune & thymic

Enfuvirtide

Also: Fuzeon · T-20

Enfuvirtide (Fuzeon) is an HIV fusion inhibitor, a peptide that blocks the virus from entering cells. It is approved as part of combination antiretroviral therapy for treatment-experienced adults who still have HIV replication. It is given by subcutaneous injection. The Watchlist boundary is keeping it to its approved HIV treatment role and noting the near-universal injection-site reactions.

Approved for specific usesPost-market evidenceSafety / regulatory watch

The verdict

Our read at a glance.

Whether enfuvirtide's approved role in combination HIV therapy is understood within that specific treatment-experienced setting, rather than generalized.

The signal
Randomized trials, including the TORO studies, showed enfuvirtide added to an optimized background regimen improved viral suppression in treatment-experienced patients. It is used in combination, not as monotherapy.
The unknown
Its place now that many oral options and newer agents exist, given that it requires twice-daily injections and causes frequent injection-site reactions.
Our read
A specific HIV salvage drug used in combination, not a general antiviral. Enfuvirtide has real trial support for treatment-experienced HIV, but the injection burden and side effects keep it a targeted option.

The mechanism

How it works.

Enfuvirtide is a synthetic 36-amino-acid peptide copied from a stretch of HIV's gp41 fusion protein. It binds the matching region of gp41 on the virus, jamming the hairpin folding motion the protein must complete to pull the viral and cell membranes together. With fusion blocked, the virus cannot enter and infect a new T cell, and it is used in combination when other antiretrovirals have failed.

Safety & regulatory boundary

The consequential part.

Enfuvirtide causes injection-site reactions in nearly all users, can increase the risk of bacterial pneumonia, and has been linked to hypersensitivity reactions. It is approved only as part of combination HIV therapy in treatment-experienced patients, not as a standalone or preventive agent. Fuzeon is the approved product and is not the same as compounded or research-labeled enfuvirtide.

What's next

What we're watching.

Its role relative to newer entry inhibitors and long-acting agents, and adherence given the injection burden.

Context

Why this is discussed.

Enfuvirtide was the first HIV entry and fusion inhibitor and is a salvage option when other antiretrovirals have failed.

The evidence base

20 cited references.

Registered trials8

Intensification With Enfuvirtide in Naive HIV-infected Patients (ANRS130)

ClinicalTrials.gov · PHASE3 · COMPLETED · 2006-04

Raltegravir in Patients With End Stage Liver Disease and in Transplant Recipients

ClinicalTrials.gov · PHASE1/PHASE2 · COMPLETED · 2010-05

Efficacy and Tolerance of the Switch From Enfuvirtine to Raltegravir in Antiretroviral Therapy Regimen in HIV Patients With Undetectable Viral Load

ClinicalTrials.gov · PHASE3 · COMPLETED · 2007-05

Early Intensification of Antiretroviral Therapy Including Enfuvirtide in HIV-1-Related Progressive Multifocal Leucoencephalopathy (ANRS125)

ClinicalTrials.gov · PHASE2 · COMPLETED · 2005-04

Trial to Evaluate the Interest of a Reductive Anti Retroviral Strategy Using Dual Therapy Inspite of Triple Therapy

ClinicalTrials.gov · PHASE3 · COMPLETED · 2014-12

Study to Compare Bictegravir/Lenacapavir Versus Current Therapy in People With HIV-1 Who Are Successfully Treated With a Complicated Regimen

ClinicalTrials.gov · PHASE2/PHASE3 · ACTIVE_NOT_RECRUITING · 2022-08-16

Optimized Antiretroviral Therapy During Allogeneic Hematopoietic Stem Cell Transplantation in HIV-1 Individuals

ClinicalTrials.gov · EARLY_PHASE1 · COMPLETED · 2013-06

Optimizing Treatment for Treatment-Experienced, HIV-Infected People

ClinicalTrials.gov · PHASE3 · COMPLETED · 2008-01

Indexed literature (PubMed)12

Enfuvirtide

PubMed · 2006

Antiviral Agents

PubMed · 2012

Enfuvirtide

Chen RY et al. · Expert Opin Investig Drugs · 2002

Enfuvirtide

PubMed · 2012

Enfuvirtide

Lalezari JP et al. · Drugs Today (Barc) · 2004

HIV entry inhibitors

Esté JA et al. · Lancet · 2007

Enfuvirtide

Dando TM et al. · Drugs · 2003

New antiretroviral drugs

Gulick RM · Clin Microbiol Infect · 2003

Efficacy of new antiretroviral drugs in treatment-experienced HIV-infected patients: a systematic review and meta-analysis of recent randomized controlled trials

Pichenot M et al. · HIV Med · 2012

Anti-HIV drugs

De Clercq E · Verh K Acad Geneeskd Belg · 2007

Emerging anti-HIV drugs

De Clercq E · Expert Opin Emerg Drugs · 2005

Virus Entry Inhibitors: Past, Present, and Future

Su S et al. · Adv Exp Med Biol · 2022

Keep reading

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