The AIDS Beacon™

Description

Fuzeon is the first fusion inhibitor approved by the U.S. Food and Drug Administration for patients who have already started antiretroviral therapy for HIV infection. Fusion inhibitors are drugs that disable HIV from “fusing,” or binding, to healthy CD4 cells in HIV-positive patients. Fuzeon must be used in combination with other drugs – usually three or four – in a regimen known as Highly Active Antiretroviral Treatment (HAART).

Fuzeon is an option for patients who don’t respond well to other HIV treatments or have developed resistance to other HIV drugs. The FDA has not approved Fuzeon for HIV-positive patients beginning drug therapy for the first time. Fuzeon is only approved to treat adults or children ages 6 years or older for HIV-1.

Mechanism of Action

Fuzeon prevents HIV from infecting healthy CD4 cells by binding to the virus’s “gp41” protein on the surface of the virus. This prevents HIV copies from attaching to the surface of CD4 cells. Currently, Fuzeon is the only FDA approved fusion inhibitor in the Entry Inhibitor drug class. The drug is unique for its ability to target the virus’s protein to prevent membrane fusion (binding and fusing) rather than proteins on the surface of the human cell.

By disabling HIV infections in CD4 cells, Fuzeon may improve CD4 count because healthy cells are able to divide into new, uninfected daughter cells. This also results in a decrease of viral load.

History

The active ingredient in Fuzeon, enfuvirtide (T-20), was created by the pharmaceutical company Trimeris in 1996. Three years later, Trimeris partnered with Hoffmann-La Roche Inc. to develop the drug further. Fuzeon was approved by the FDA on March 15, 2003 as a treatment component for HIV-1 in patients who have already undergone antiretroviral therapy.

Usage in HIV

Fuzeon is often an option for patients unresponsive to previous antiretroviral treatments. For the best results, researchers suggest taking Fuzeon with other HIV drugs that are still fully or moderately effective in treating HIV if a patient has developed resistance to other antiretroviral drugs. Although Fuzeon is an alternative to drugs an individual has developed resistance to, it should be taken with other medications with little resistance to achieve the best possible outcome.

Dosage and Administration

Fuzeon cannot be taken in pill form because it has a fragile structure. Instead, the drug must be injected under the skin twice daily. Ninety milligrams (mg) of Fuzeon is considered one dose – making daily intake of the drug 180 mg for individuals receiving the treatment. The drug can be injected into areas near the lower stomach, upper arm, or upper leg. To prevent infection or irritation, individuals should avoid using the same injection sites more than once in a day or two.

The drug is originally packaged as two separate vials: one with the drug in powder form, and another with sterilized water to mix with the powder. Both vials must be stored at room temperature (59 to 86 degrees Fahrenheit) or in a refrigerator if room temperature storage is not an option. To prepare a dose, the contents of the water vial must be transferred and mixed with the powder in the opposite vial with a sterile syringe. For best results, the powder must be completely dissolved in the liquid.

If a dose is mixed, it must either be used immediately or stored for use up to 24 hours in the refrigerator. Food does not affect Fuzeon, so patients can take the drug on an empty or full stomach.

Taking Fuzeon regularly is important for the health of the patient using the drug. If doses are missed or skipped, patients are at an increased risk of HIV developing resistance to Fuzeon, making the virus harder to treat. If a patient misses a dose, he or she should prepare and inject the dose as soon as possible. If the missed dose is close to the next planned one, do not take two doses. Instead, wait 12 hours to administer more of the drug.

Like all other injectable medications, patients should carefully handle and dispose used syringes in specialized containers for sharp objects. Syringes should never be thrown in the trash can. Patients should talk to their doctor or pharmacist about obtaining a specialized container and how to dispose of used syringes.

For children ages 6 to 16 years, dosage is calculated by weight. For every kilogram of a child’s weight, two milligrams of Fuzeon are measured and administered. Children should still take two doses per day without exceeding 90 milligrams of the drug.

Since Fuzeon can be difficult to prepare and administer, Roche offers a free support program for patients taking or starting the drug. The Nurse Connections Program is dedicated to helping patients prepare Fuzeon vials for use. The program connects patients to nurses who visit patients at home and teach them how to inject properly. In addition, the program has an assistance hotline staffed by nurses to answer any questions patients have about the drug, including how to prepare and administer Fuzeon.

Side Effects

Irritation and inflammation of injection sites are common side effects from using Fuzeon. Pain, discomfort, hardened skin, redness, bumps, itching, and swelling may occur. Contact a physician immediately if a severe skin reaction develops or if these symptoms last more than seven days.

Results from a clinical trial by Hoffmann-La Roche recorded two cases of bacterial pneumonia thought to result from the use of Fuzeon. One patient with the condition discontinued treatment and subsequently died. Bacterial pneumonia did not occur in the other control groups of the study who were taking other HIV medications, but not Fuzeon. At this time, researchers do not know the relationship between Fuzeon and bacterial pneumonia. Notify a physician immediately if a cough, fever, or issues with breathing arise.

More common side-effects include peripheral neuropathy (damage to nerves in the brain and spinal cord), insomnia, depression, decreased appetite, fatigue, muscle pain, constipation, sinus problems, enlarged lymph nodes, loss of weight, weakness or loss of strength, pancreas problems, and glomerulonephritis – inflammation of the glomeruli (small blood vessels in the kidneys).

In rare cases, some patients have allergic reactions to the drug. Symptoms of an allergic reaction to Fuzeon include rash, trouble breathing, fever with vomiting, nausea, blood in the urine, swelling of the feet, chills, shaking, low blood pressure, and increased liver enzymes.

Drug Interactions

Fuzeon is not known to interact with the effectiveness of other medications, including other HIV drugs, but the drug can negatively affect some medical conditions. Patients who are allergic to any of Fuzeon’s ingredients should not consider taking it. Because each person has a different reaction or sensitivity to drugs, patients should discuss all medical conditions and both over-the-counter and prescription medications while taking Fuzeon. Similarly, patients taking the drug should talk to a physician about alcohol consumption and if adverse reactions occur.

Precautions

Women who are pregnant or breastfeeding should talk to a doctor about taking Fuzeon. The FDA lists Fuzeon as a “Category B” threat, which means that animal trials have shown that Fuzeon was no risk to fetuses; however, there have been no such controlled studies on pregnant woman. Although it is not clear whether Fuzeon can be transferred through breast milk, HIV-positive women should not breastfeed because of the possibility of the virus being transferred to the child.

Patients should discuss their medical conditions with their doctors before and while using the drug. Although Fuzeon increases CD4 counts and decreases viral loads, patients can still experience opportunistic infections. Fuzeon does not slow the transmission of HIV, so patients must continue to use condoms or other forms of protection to prevent transmission of the virus during sexual intercourse.

Ongoing Clinical Trials:

Open:

Currently, there are four open clinical trials for Fuzeon, most for the development of new combination therapies.

Phase not determined (0):

• National Institute of Allergy and Infectious Diseases (NIAID): Safety and effectiveness of addition of maraviroc to ART regimens in HIV-infected adults with suboptimal CD4 T-cell count recovery despite sustained virologic suppression (NCT00709111)

Phase 2:

• Canadian Immunodeficiency Research Collaborative: Study to assess safety and quality of life of patients using biojector versus needles for Fuzeon administration (NCT00333736)

Phase 2/3:

• University of California, San Diego: Clinical trial of CNS-targeted HAART (CIT2) (NCT00624195)

Phase 3:

• National Institute of Allergy and Infectious Diseases (NIAID): Optimizing treatment for treatment-experienced, HIV infected people (NCT00537394)

Closed:

Phase not determined:

• Institute for Interdisciplinary Infectiology: Cohort study for patients using Fuzeon (NCT00216359)

• National Institute of Allergy and Infectious Diseases (NIAID): Effect of a Fuzeon-based anti-HIV drug regimen on latent HIV reservoirs in treatment naive adults (NCT00051831)

• National Institute of Allergy and Infectious Diseases (NIAID): Treatment Intensification for HIV Infected Patients With Multi-Drug Resistant Virus (NCT00102934)

Phase 2:

• Hoffmann-La Roche: INNOVE Study: A study of 3 months induction with Fuzeon + Optimized Background (OB) versus OB alone in HIV-1 infected patients with virological failure (NCT00615134)

Phase 3:

• French National Agency for Research on AIDS and Viral Hepatitis: Intensification with Fuzeon in naive HIV-infected patients (ANRS130) (NCT00302822)

For a more detailed listing of clinical trials involving Fuzeon, please see the U.S. government clinical trials Web site.

Clinical Trial Results:

A study to evaluate the safety and efficacy of adding Fuzeon to oral highly active antiretroviral therapy (HAART) in human immunodeficiency virus (HIV) patients with prior treatment experience (2008): The study compared patients taking Fuzeon with HAART to the results of patients taking HAART alone. Fuzeon used with HAART resulted in better viral suppression. A summary of the study can be found at the Clinical Trials Web site.

BLQ Study: A study of a protease inhibitor with Fuzeon in treatment-experienced patients with HIV-1 (2006): The experimental study measured the safety and effectiveness of Fuzeon with developing protease inhibitors. The study confirmed that Fuzeon is a safe and effective addition to protease inhibitor treatments. A summary of the study can be found at the Clinical Trials Web site.

Fuzeon, an HIV-1 fusion inhibitor, for drug-resistant HIV infection in North and South America (also known as the TORO 1 study group) (2003): Along with the TORO 2 study group, this Phase 3 study of Fuzeon was the basis for FDA approval of the drug in 2003. Researchers found that when the drug was used with other HIV medications, viral load decreased more and CD4 cells increased in comparison to treatments undergone over the course of at least six months by the same patients. Patients were twice as likely to achieve undetectable plasma levels of HIV in comparison to patients receiving an antiretroviral alone. These patients were previously treated with three classes of other antiretroviral drugs, with some patients having developed resistance to other HIV drugs. The study can be found in the New England Journal of Medicine.

Efficacy of Fuzeon in patients infected with drug-Resistant HIV-1 in Europe and Australia (also known as the TORO 2 study group) (2003): This Phase 3 study concluded that an optimized background regimen with Fuzeon was effective in combination with other HIV medications in decreasing viral load and increasing CD4 cell count.  The study can be found in the New England Journal of Medicine.

Patient Assistance Programs:

Roche Patient Assistance Foundation
877-757-6243
http://www.rocheusa.com/programs/patientassist.asp

Fuzeon Reimbursement Assistance Program
877-4FUZEON
http://www.fuzeon.com/consumer/reimbursement_assistance.aspx

Roche Nurse Connections Program
877-438-9366
http://www.fuzeon.com/consumer/fuzeon_nurse_connections.aspx

Links of Interest

Fuzeon Product Web site
http://www.fuzeon.com/

Disposing of used needles responsibly
http://www.rocheusa.com/sharps/index.asp

The FDA approves Fuzeon
http://www.fda.gov/ForConsumers/ByAudience/ForPatientAdvocates/HIVandAIDSActivities/ucm125088.htm

Roche’s Detailed Information on Fuzeon for Patients and Caregivers
http://www.rocheusa.com/products/fuzeon/ppi.pdf