Important note: Information in this article was accurate in March 2003. The state of the art may have changed since the publication date.
Treatment Issues: Newsletter of Experimental AIDS Therapies - Volume 17, Number 3, March 2003
Fuzeon was approved in the U.S. primarily on the basis of 24-week efficacy and safety data from two large clinical trials called TORO 1 and TORO 2 (T-20 versus Optimized Regimen Only, 1 and 2)
HIV-positive people with current viral load over 5000 copies and experience with all three classes of antiretroviral drugs (ARV) were recruited for the trials and evaluated for drug resistance during a six-week screening period. On average, participants had CD4 counts below 100, viral loads above 100,000 and had used 12 antiretroviral drugs in the past. An optimized regimen (OR) was selected by the patient and doctor based on resistance results, treatment history and tolerability experience. On average, the OR contained 4 drugs (patients in TORO 1 were sensitive to fewer than 2 of their drugs, on average). Patients were then randomly assigned to either start their OR along with twice-daily T-20 injections or to start the OR alone. All in all, the participants in these trials had fairly advanced HIV disease, were highly treatment-experienced and had less than perfect susceptibility to the best available antiretroviral regimens. Twenty-four week data are shown here but both trials were continued and will eventually report 48-week data.
The primary measure of efficacy in these trials was the difference at 24 weeks between viral load reductions in those taking the OR plus T-20 and those on the OR alone.
In addition, the studies evaluated how many in each group had viral load go below 50 copies and how many went below 400 copies. CD4 count changes were also reported.
TORO 1
TORO 1 was conducted in the U.S., Canada, Mexico and Brazil. A final report of 24-week data was published in the New England Journal of Medicine (NEJM), March 2003. This trial involved 491 people.
| Primary Result: (log10 copies) | T-20 + OR | OR (OR=Optimized Regimen) |
| Drop in viral load from baseline: | -1.70 | -0.76 |
Secondary Results: |
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| Percent below 50 copies: | 20% | 7% |
| Percent below 400 copies: | 32% | 16% |
| Increase in CD4 count: | +76 cells | +32 cells |
TORO 2
TORO 2 was conducted in Europe and Australia. A preliminary report of 24-week data was presented at the International AIDS Conference in Barcelona, July 2002. Publication of final 24-week results is expected soon. This trial involved 504 people.
| Primary Result: (log10 copies) | T-20 + OR | OR |
| Drop in viral load from baseline: | -1.43 | -0.65 |
Secondary Results: |
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| Percent below 50 copies: | 12% | 5% |
| Percent below 400 copies: | 28% | 12% |
| Increase in CD4 count: | +65 cells | +38 cells |
Safety
Pooled safety data from both TORO 1 and TORO 2 were reported in the NEJM article.
There was little difference between the frequency and severity of the most common treatment-associated side effects in the T-20 group and the OR group and people taking T-20 actually had slightly less nausea and diarrhea.
Local injection site reactions were the most frequent adverse events associated with the use of T-20. In Phase III clinical studies, 98 percent of patients had at least one local injection site reaction. Manifestations of injection site reactions may include pain and discomfort, hardness, redness, nodules and cysts, itching, and bruising.
Hypersensitivity reactions have been associated with T-20 therapy (less than 1 percent) and have recurred on rechallenge. Symptoms of an allergic reaction may include rash, fever, nausea and vomiting, chills, rigors, low blood pressure, and elevated serum transaminases. In addition, an increased rate of bacterial pneumonia was observed in patients treated with T-20 in the Phase III clinical trials compared to the control arm. It is unclear if the increased incidence of pneumonia is related to T-20 use.
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