PRNewswire - November 18, 2004

RESIST-2 enrolled 863 patients in Europe and Latin America. Data from RESIST-1, a related study conducted in 620 patients in the United States, Canada and Australia, was presented earlier this year at the 44th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). 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-2 study (1182.48), treatment response, defined as 1 log(10) or greater decrease in viral load from baseline, was achieved by 41.0% of patients who received tipranavir/r, versus 14.9% of patients treated in the comparator protease inhibitor boosted with low-dose ritonavir (CPI/r) arm (p<0.001).

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/mm3 and 1 cell/mm3, respectively (p=0.02).

A subset of the study population received enfuvirtide as part of their treatment regimen. For these patients, who were generally more immunocompromised, 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 remain statistically significant. Baseline characteristics, including median viral load and CD4+ cell count, were similar for patients in the tipranavir/r and the CPI/r groups. RESIST-2 examined patients with advanced HIV disease who, on average, had received 12 antiretroviral drugs, were experiencing virologic failure, and had documented PI resistance.

"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." 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 remained on treatment without study discontinuation.

"Boehringer Ingelheim is pleased about the presentation of the preliminary results from RESIST-2," 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, coupled with the recent submission of the NDA and presentation of interim results from RESIST-1, brings us one step closer to providing tipranavir to patients in need of new treatment options."

Study Design

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 3 trial designed to study the safety and efficacy of tipranavir, boosted with low-dose ritonavir, versus a CPI, boosted with low-dose ritonavir, in treatment-experienced patients with documented PI resistance. All patients had baseline genotypic testing prior to randomization to aid investigators in the selection of the CPI/r.

Patients enrolled in RESIST-2 were randomized to receive a twice-daily dose of tipranavir/r 500mg/200mg or a CPI/r at its standard boosting dose. CPIs included lopinavir, saquinavir, amprenavir and 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

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 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 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

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, please visit http://us.boehringer-ingelheim.com.

Reference:

Abstract : PL 14.3. 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; November 14 - 18, 2004, Glasgow, U.K.

SOURCE Boehringer Ingelheim

Web Site: http://us.boehringer-ingelheim.com

041118
PR041138

Always watch for outdated information. This article first appeared in 2004. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 2004. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .