The data indicated that combination therapy with T-20 reduced HIV to undetectable levels in the blood in at least twice the percentage of patients than those who did not take the drug. Results of the studies initially were reported earlier this year. (See BioWorld Today, May 17, 2002, and April 19, 2002.)
The data were presented in Barcelona, Spain, at the XIV International AIDS Conference, which runs through Friday.
Trimeris, of Durham, N.C., said those receiving T-20 were less likely to experience virological failure or relapse over 24 weeks.
TORO 1 enrolled 491 patients who had been treated with 12 antiretroviral agents. Patients who received T-20 as part of their combination regimen achieved a reduction in HIV levels of 1.697 log10 copies/mL, compared to 0.763 log10 copies/mL for those in the control arm. Fifty-two percent of patients receiving T-20 experienced a 1.0 log10 or greater reduction in HIV levels.
TORO 2 enrolled 504 patients who previously had been treated with 11 antiretroviral drugs. Twenty-eight percent of patients who received T-20 in combination with an optimized background regimen had undetectable blood levels (less than 400 copies/mL) of HIV at 24 weeks, compared to 14 percent receiving an optimized background regimen alone (p<0.0001). Combination therapy with T-20 further reduced HIV viral load to less than 50 copies/mL in 12 percent of patients, compared to 5 percent who took combination therapy alone (p=0.0099).
Co-developed by Hoffmann-La Roche Inc., of Nutley, N.J., T-20 is the most clinically advanced in an investigational class of HIV drugs called fusion inhibitors. Unlike existing anti-HIV drugs, which target viral enzymes involved in replication of the virus, T-20 is designed to block HIV from fusing with a host cell.
In other news from the conference:
Abbott Laboratories, of Abbott Park, Ill., said data showed the three-year efficacy and tolerability in an ongoing Phase II study of a Kaletra-based regimen in 100 patients new to antiretroviral therapy provided viral suppression, as measured by viral load, and immunologic response, as measured by CD4 levels. Of the six patients who experienced viral rebound (HIV RNA >400 copies/mL) and had genotypic analysis available, none showed detectable protease inhibitor-resistant mutations through the three years of study. In an intent-to-treat analysis, 75 percent of patients maintained undetectable viral loads. Kaletra was approved for marketing by the FDA in September 2000.
AnorMED Inc., of Vancouver, British Columbia, reported that it identified a new lead drug candidate for HIV called AMD-070, one of a new class of HIV entry inhibitors that target CXCR4, a chemokine receptor. In order to enter and infect cells, HIV must bind to either the CXCR4 or CCR5 chemokine receptor. The company said different strains of HIV prefer one receptor or the other. Blocking the CXCR4 and CCR5 receptors can prevent the relevant HIV strains from entering and infecting the target cells, the company said.
Boehringer Ingelheim Pharmaceuticals Inc., of Ridgefield, Conn., said its Phase II study of tipranavir demonstrated a significant reduction in HIV-1 levels in patients who previously had received treatment with multiple protease inhibitor-based regimens. Patients with 11 to 20 PI mutations at baseline achieved a 1.77 to 2.56 log10 reduction in HIV-1 viral levels, it said.
Gilead Sciences Inc., of Foster City, Calif., reported 48-week results from an ongoing Phase III trial comparing Viread (tenofovir disoproxil fumarate) in terms of efficacy and safety to stavudine when used as part of a first-line treatment regimen. The data, which will be presented Friday, are from Study 903, a three-year, randomized, double-blind, active-controlled trial. The trial was designed to compare the efficacy and safety of a treatment regimen of Viread, lamivudine and efavirenz to a regimen of stavudine, 3TC and efavirenz in 600 patients. In the analysis of the intent-to-treat population, 87 percent of patients in both the Viread arm and the stavudine arm achieved suppression of HIV RNA below 400 copies/mL, the primary efficacy endpoint, following 48 weeks of treatment. When missing data are excluded, 95 percent of patients receiving Viread compared to 96 percent of patients receiving stavudine had reductions in HIV RNA to below 400 copies/mL.
Hollis-Eden Pharmaceuticals Inc., of San Diego, reported preliminary data from a Phase II trial conducted in South Africa in HIV-infected patients treated with HE2000, a immune-regulating hormone. Findings included a downward slope in viral load during the study period in the 100-mg dose group (0.45 log). However, in the 50-mg dose group there was a statistically significant downward slope in viral load vs. placebo (p<0.01). HE2000-treated patients also experienced increases in a number of cell types associated with innate and adaptive cell-mediated immunity throughout the study, including killer cells, dendritic cells and Th1 cells. The changes in the 18 treated patients were statistically significant vs. the six placebo patients (p<0.05).
International HIV Resistance Response Database Initiative, or RDI, is a new initiative in HIV management presented at the conference. RDI will combine data from thousands of HIV patients around the world into a freely accessible database that could enhance the ability of physicians to choose the most effective drugs. The RDI is made up of a group of individuals, companies and institutions that are pooling data from thousands of patients, in particular, their genotype, the drugs used in their treatment and their response to those drugs as determined by the amount of virus in their blood. RDI was started by Visible Genetics Inc., of Toronto.
Panacos Pharmaceuticals Inc., of Gaithersburg, Md., made its first public presentation on its drug candidate, PA-457, which the company said is the first in a new class known as budding inhibitors. Budding is the final step in HIV infection of a human cell, when newly formed virus particles are released to spread throughout the body and infect new cells. The company said PA-457 inhibits HIV infection in vitro and that the compound retains its potency against virus isolates that are resistant to all classes of approved drugs.
Progenics Pharmaceuticals Inc., of Tarrytown, N.Y., reported additional results from the ongoing Phase II studies of its investigational viral entry inhibitor, PRO 542. It said the data support the company's efforts to demonstrate that PRO542 produces an antiviral response in HIV-infected individuals for whom available antiretroviral medications have failed. Single doses of PRO 542 reduced viral concentrations by 60 percent to 80 percent on average for approximately five weeks in treatment-experienced patients, the company said.
The Immune Response Corp., of Carlsbad, Calif., presented data suggesting that Remune induced helper T-cell immune responses aimed specifically at HIV in chronically infected HIV-positive individuals taking highly active antiretroviral therapy (HAART). Helper T-cell responses are thought to be important in controlling HIV-1 infection. All five patients treated with Remune showed a significant increase (p=0.008) in helper T-cell immune response against HIV-1. None of the patients receiving placebo exhibited helper T-cell responses. The drug has completed a Phase II trial, which the company initially reported as a failure, and later recharacterized as a success. (See BioWorld Today, Aug. 31, 2002.)
ViroLogic Inc., of South San Francisco, reported that research published in this week's issue of the Journal of the American Medical Association indicated that resistance testing should play a greater role in guiding treatment for newly infected HIV patients. The study used ViroLogic's PhenoSense HIV drug resistance assay. Researchers found that the percentage of newly infected patients harboring resistant virus is rising, from less than 10 percent in 1998-99 to 16 percent in 2001. Transmission of virus resistant to non-nucleoside reverse transcriptase inhibitors experienced a particularly steep rise during that period, the company said, important because many HIV physicians prescribe NNRTIs as first-line treatment after an HIV diagnosis.
Visible Genetics Inc., of Toronto, presented new data confirming that its interpretation system, part of the Trugene HIV-1 genotyping kit, is able to predict how patients will respond to different HIV drugs. Data demonstrated that genotyping, with interpretation by VGI's GuideLines version 3, was more highly predictive of response to therapy than phenotyping.