Boehringer Ingelheim Announces 24-Week Interim Results from Second Phase III Pivotal Study of Tipranavir

GLASGOW, Scotland -- New data from a pivotal Phase III study (RESIST-2) show 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 one 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 Seventh International Congress on Drug Therapy in HIV Infection.

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 percent 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 percent of participants in the tipranavir/r group and 13.1 percent of participants in the CPI/r group achieved viral loads of less than 400 copies/mL, and 22.5 percent vs. 8.6 percent 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 one 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 percent in the tipranavir/r arm vs. 13.0 percent in the CPI/r arm achieved a viral load of less than 400 copies/mL and 23.1 percent vs. 4.3 percent 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 III 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.

Source: Boehringer Ingelheim