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Boehringer Ingelheim Announces 24-Week Interim Results from Tipranavir RESIST-1 Phase 3 Study
Washington, November 1 (ots/PRNewswire) - New data from a pivotal Phase 3 study (RESIST-1) demonstrate that a statistically significant greater percentage of HIV-positive patients taking a tipranavir-based regimen achieved a treatment response versus those taking a regimen containing one of several marketed protease inhibitors (PIs). Treatment response in this study of treatment-experienced patients was defined as a 1 log(10) or greater decrease in viral load from baseline. Tipranavir is an investigational non-peptidic protease inhibitor that requires boosting with low-dose ritonavir. These data were presented at the 44th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC).
RESIST-1 was conducted in 620 patients in the United States, Canada, and Australia. A related study, RESIST-2, enrolled 863 patients in Europe and Latin America. The interim analyses of RESIST-1 and RESIST-2 formed the foundation of the New Drug Application (NDA), which was submitted to the U.S. Food and Drug Administration (FDA) for marketing approval of tipranavir on October 22, 2004.
In the RESIST-1 study (1182.12), treatment response, defined as a 1 log10 or greater decrease in viral load from baseline, was achieved by 41.5% of patients who received tipranavir/r, versus 22.3% of patients in the comparator protease inhibitor boosted with low-dose ritonavir (CPI/r) arm (p<0.0001). Moreover, a greater proportion of patients receiving tipranavir therapy achieved a viral load below the level of quantification than those who were treated with a CPI/r.
At 24 weeks, 34.7% of participants in the tipranavir/r group and 16.5% of participants in the CPI/r group achieved viral loads of less than 400 copies/mL, and 25.1% vs. 10% achieved less than 50 copies/mL (p<0.001). Patients who received enfuvirtide as part of their treatment were generally more immuno-compromised. For these patients, their response rates improved to 47.1% vs. 21.9% (<400 copies/mL) and 32.8% vs. 14.3% (<50 copies/mL). These differences remain statistically significant.
Patients taking tipranavir/r also experienced greater increases in their CD4+ cell count than those taking a CPI/r, with CD4+ increases of 36 cells/mm3 and 6 cells/mm3, respectively (p<0.001).
"RESIST-1 examined patients with advanced HIV disease who, on average, previously received 12 antiretroviral drugs, were experiencing virologic failure, and had documented PI resistance," said Charles Hicks, M.D., Associate Professor of Medicine in the Division of Infectious Diseases at Duke University Medical Center. "These data suggest that tipranavir could have the potential to advance the care of treatment-experienced patients."
The tipranavir/r adverse event profile was similar to events observed in the CPI/r group through 24 weeks. The participants in the tipranavir/r group experienced a higher rate of liver enzyme and lipid elevations; however, most laboratory abnormalities were asymptomatic and most patients were successfully treated without treatment discontinuation.
"Boehringer Ingelheim is pleased about the encouraging preliminary results from RESIST-1," 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. "This important milestone brings us one step closer to providing tipranavir to patients in need of new HIV treatment options."
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-1 is a randomized, controlled, open-label Phase 3 trial designed to study the safety and efficacy of tipranavir, boosted with low-dose ritonavir, versus a low-dose ritonavir-boosted CPI in treatment-experienced patients with documented PI resistance. All patients had baseline genotypic resistance testing prior to randomization to aid investigators in the selection of the CPI/r.
Patients enrolled in RESIST-1 were randomized to receive a 500mg/200mg twice-daily dose of tipranavir combined with ritonavir or a CPI combined with ritonavir at its standard boosting dose. CPIs included lopinavir, saquinavir, amprenavir or indinavir. All patients combined their PI with an optimized background regimen (OBR) of anti-HIV medications. The OBR was selected on the basis of treatment history and baseline genotypic resistance testing. The use of enfuvirtide was allowed, but had to be selected by investigators prior to randomization.
Tipranavir is a non-peptidic protease inhibitor currently in late Phase 3 clinical development - the final stage of clinical testing prior to FDA review. Tipranavir is also being evaluated for use in pediatric and treatment-naïve patient populations in Phase 2 studies that are currently underway.
Based on available clinical and in vitro data, tipranavir appears to remain active against strains of HIV-1 that are resistant to commercially available protease inhibitors. Ongoing clinical studies are designed to confirm these data.
In studies to date, the most commonly reported adverse events are gastrointestinal-related and include diarrhea, nausea, fatigue, headache and vomiting. The most common laboratory abnormalities are elevated liver enzymes (AST/ALT) and triglycerides.
Tipranavir does not cure HIV infection/AIDS or prevent the transmission of HIV to others.
Boehringer Ingelheim is committed to the research and development of novel antiretroviral agents. VIRAMUNE(R) (nevirapine), a product of original research done at Boehringer Ingelheim, was the first member of the non-nucleoside reverse transcriptase inhibitor (NNRTI) class of anti-HIV drugs. Boehringer Ingelheim is involved in basic research and is committed to the development of tipranavir and improving HIV therapy by providing physicians and patients with innovative antiretrovirals.
For more information on Boehringer Ingelheim Pharmaceuticals, Inc., please visit http://us.boehringer-ingelheim.com.
Hicks et al. RESIST-1: A Phase 3 Randomized, Controlled, Open-Label Multicenter Trial Comparing Tipranavir/Ritonavir (TPV/r) to an Optimized Comparator Protease Inhibitor/r (CPI/r) Regimen in Antiretroviral (ARV) Experienced Patients: 24-Week Data, 44th Interscience Conference on Antimicrobial Agents and Chemotherapy; October 31 - November 2, 2004, Washington, D.C. Abstract #3726
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