18.11.2004 – 12:25
Boehringer Ingelheim Announces 24-Week Results From Second Phase III Pivotal Study of Tipranavir
Glasgow, Scotland, November 18 (ots/PRNewswire)
- RESIST-2 Data Demonstrate Efficacy in Treatment-Experienced Patient Population
New tipranavir pivotal Phase III data show that a statistically significant higher percentage of treatment-experienced HIV-positive patients taking tipranavir therapy achieved treatment response versus those taking other currently available protease inhibitors. Tipranavir is an investigational non-peptidic protease inhibitor in development by Boehringer Ingelheim. These data from the RESIST-2 study were presented at the 7th International Congress on Drug Therapy in HIV Infection in Glasgow.
In RESIST-2 (1182.48), treatment response was achieved by 41.0% of patients who received tipranavir boosted with low-dose ritonavir (tipranavir/r) compared to 14.9% of patients treated with a comparator protease inhibitor boosted with low-dose ritonavir (CPI/r) (p<0.001). Treatment response was defined as a 1 log(10) or greater decrease in viral load from baseline over 24 weeks.
Moreover, a greater proportion of patients receiving tipranavir/r achieved a viral load below the level of quantification than those who were treated with a CPI/r. At 24 weeks, 33.6% of participants in the tipranavir/r group and 13.1% of participants in the CPI/r group achieved viral loads of less than 400 copies/mL, and 22.5% vs. 8.6% achieved less than 50 copies/mL (p<0.0001). Patients taking tipranavir/r also experienced greater increases in their CD4+ cell count than those taking a CPI/r, with CD4+ increases of 31 cells/mm(3) and 1 cell/mm(3), respectively (p=0.02).
A subset of the study population received enfuvirtide as part of their treatment regimen. Of these patients, who generally had more impaired immune systems, 38.5% in the tipranavir/r arm vs. 13.0% in the CPI/r arm achieved a viral load of less than 400 copies/mL, and 23.1% vs. 4.3% achieved less than 50 copies/mL. These differences are statistically significant.
The RESIST-2 study was conducted in 863 patients in Europe and Latin America. Baseline characteristics, including median viral load and CD4+ cell count, were similar for patients in the tipranavir/r and the CPI/r groups. Patients in the study had received, on average, 11 previous antiretroviral drugs, were experiencing virologic failure, and had documented PI resistance.
The adverse event profile of the tipranavir/r group was similar to the CPI/r group through 24 weeks. The tipranavir/r group experienced a higher rate of liver enzyme and lipid elevations; however, most laboratory abnormalities were asymptomatic and most patients remained on treatment without permanent discontinuation.
"There is an increasing need for treatments that are effective in combating drug resistant virus," said Dr. Pedro Cahn of the Fundacion Huesped, Buenos Aires, Argentina. "The RESIST-2 data suggest that tipranavir may have the potential to improve the care of treatment-experienced patients."
A related Phase III pivotal study, RESIST-1, was conducted in 620 patients in the United States, Canada and Australia. RESIST-1 study results were presented last month at the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in Washington, DC. Data from RESIST-1 and RESIST-2 formed the foundation of the submission packages to international regulatory authorities for marketing approval of tipranavir.
"Boehringer Ingelheim is pleased by the interim results from the RESIST-2 pivotal study," said Dr. Andreas Barner, Vice-Chairman of the Board of Managing Directors and Head of Corporate Board Division Pharma Research, Development and Medicine at Boehringer Ingelheim. "These results, combined with those from RESIST-1, suggest that tipranavir may offer the international HIV community a much needed treatment option for patients whose virus is resistant to available protease inhibitors."
The RESIST (Randomized Evaluation of Strategic Intervention in Multi-Drug ReSistant Patients with Tipranavir) clinical trial program is one of the largest study programs undertaken with an investigational antiretroviral agent in patients previously treated with multiple combinations of antiretroviral drug regimens.
RESIST-2 is a randomized, controlled, open-label Phase III trial designed to study the efficacy and safety of tipranavir, boosted with low-dose ritonavir, versus a low-dose ritonavir-boosted comparator PI in treatment-experienced patients with documented PI resistance. All patients received baseline genotype testing prior to randomization to aid investigators in the selection of the comparator PI.
Patients enrolled in RESIST-2 were randomized to receive an optimized standard of care regimen containing tipranavir/r 500mg/200mg twice daily or a CPI/r at its standard dose. CPIs included lopinavir, saquinavir, amprenavir and indinavir. Optimized background regimens were chosen by patients' physicians on the basis of treatment history and baseline genotypic resistance testing. The use of enfuvirtide was allowed, but had to be pre-selected by investigators prior to randomization.
Tipranavir is a non-peptidic protease inhibitor currently in Phase III of clinical development. In June 2004, Boehringer Ingelheim announced the enrollment of the first patient in a broad-scale global tipranavir Compassionate Use Program, which provides access to HIV-positive patients in clinical need of new treatment options.
Tipranavir is also being evaluated for use in pediatric and treatment-naive patient populations. Phase II studies are currently underway.
Based on available clinical and in vitro data, tipranavir is active against most strains of HIV-1 that are resistant to commercially available protease inhibitors. Ongoing studies are designed to confirm these data.
In studies to date, tipranavir has been well tolerated by most patients and has a safety profile similar to other PIs. The most commonly reported adverse events across all clinical trials were gastrointestinal-related and included diarrhea, nausea, fatigue, headache and vomiting. Consistent with other PIs, the most common laboratory abnormalities were elevated liver enzymes and triglycerides.
Boehringer Ingelheim is committed to the research and development of novel antiretroviral agents. VIRAMUNE(R) (nevirapine) is a product of original research done at Boehringer Ingelheim. VIRAMUNE was the first member of the non-nucleoside reverse transcriptase inhibitor (NNRTI) class of anti-HIV drugs. Boehringer Ingelheim is committed to the rapid development of the investigational non-peptidic protease inhibitor (NPPI) tipranavir in Phase III development and the nucleoside analogue (NRTI) alovudine in Phase II development. The company is involved in basic research and is committed to improving HIV therapy by providing physicians and patients with innovative antiretrovirals.
For more information on Boehringer Ingelheim, please see http://www.boehringer-ingelheim.com/hiv .
Cahn et al. 24-week data from RESIST 2: Phase 3 study of the efficacy and safety of either tipranavir/ritonavir (TPV/r) or an optimized ritonavir (RTV)-boosted standard-of-care (SOC) comparator PI (CPI) in a large randomized multicenter trial in treatment-experienced HIV+ patients. 7th International Congress on Drug Therapy in HIV Infection, Glasgow, UK, November 18, 2004. Abstract #: PL 14.3
ots Originaltext: Boehringer Ingelheim
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