2004-11-18

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-ExperiencedPatient Population

New tipranavir pivotal Phase III data show that a statisticallysignificant higher percentage of treatment-experienced HIV-positivepatients taking tipranavir therapy achieved treatment response versusthose taking other currently available protease inhibitors.Tipranavir is an investigational non-peptidic protease inhibitor indevelopment by Boehringer Ingelheim. These data from the RESIST-2study were presented at the 7th International Congress on DrugTherapy in HIV Infection in Glasgow.

In RESIST-2 (1182.48), treatment response was achieved by 41.0% ofpatients who received tipranavir boosted with low-dose ritonavir(tipranavir/r) compared to 14.9% of patients treated with acomparator protease inhibitor boosted with low-dose ritonavir (CPI/r)(p<0.001). Treatment response was defined as a 1 log(10) or greaterdecrease in viral load from baseline over 24 weeks.

Moreover, a greater proportion of patients receiving tipranavir/rachieved a viral load below the level of quantification than thosewho were treated with a CPI/r. At 24 weeks, 33.6% of participants inthe tipranavir/r group and 13.1% of participants in the CPI/r groupachieved viral loads of less than 400 copies/mL, and 22.5% vs. 8.6%achieved less than 50 copies/mL (p<0.0001). Patients takingtipranavir/r also experienced greater increases in their CD4+ cellcount than those taking a CPI/r, with CD4+ increases of 31cells/mm(3) and 1 cell/mm(3), respectively (p=0.02).

A subset of the study population received enfuvirtide as part oftheir treatment regimen. Of these patients, who generally had moreimpaired immune systems, 38.5% in the tipranavir/r arm vs. 13.0% inthe CPI/r arm achieved a viral load of less than 400 copies/mL, and23.1% vs. 4.3% achieved less than 50 copies/mL. These differences arestatistically significant.

The RESIST-2 study was conducted in 863 patients in Europe andLatin America. Baseline characteristics, including median viral loadand CD4+ cell count, were similar for patients in the tipranavir/rand the CPI/r groups. Patients in the study had received, on average,11 previous antiretroviral drugs, were experiencing virologicfailure, and had documented PI resistance.

The adverse event profile of the tipranavir/r group was similar tothe CPI/r group through 24 weeks. The tipranavir/r group experienceda higher rate of liver enzyme and lipid elevations; however, mostlaboratory abnormalities were asymptomatic and most patients remainedon treatment without permanent discontinuation.

"There is an increasing need for treatments that are effective incombating drug resistant virus," said Dr. Pedro Cahn of the FundacionHuesped, Buenos Aires, Argentina. "The RESIST-2 data suggest thattipranavir may have the potential to improve the care oftreatment-experienced patients."

A related Phase III pivotal study, RESIST-1, was conducted in 620patients in the United States, Canada and Australia. RESIST-1 studyresults were presented last month at the Interscience Conference onAntimicrobial Agents and Chemotherapy (ICAAC) in Washington, DC. Datafrom RESIST-1 and RESIST-2 formed the foundation of the submissionpackages to international regulatory authorities for marketingapproval of tipranavir.

"Boehringer Ingelheim is pleased by the interim results from theRESIST-2 pivotal study," said Dr. Andreas Barner, Vice-Chairman ofthe Board of Managing Directors and Head of Corporate Board DivisionPharma Research, Development and Medicine at Boehringer Ingelheim."These results, combined with those from RESIST-1, suggest thattipranavir may offer the international HIV community a much neededtreatment option for patients whose virus is resistant to availableprotease inhibitors."

Study Design

The RESIST (Randomized Evaluation of Strategic Intervention inMulti-Drug ReSistant Patients with Tipranavir) clinical trial programis one of the largest study programs undertaken with aninvestigational antiretroviral agent in patients previously treatedwith multiple combinations of antiretroviral drug regimens.

RESIST-2 is a randomized, controlled, open-label Phase III trialdesigned to study the efficacy and safety of tipranavir, boosted withlow-dose ritonavir, versus a low-dose ritonavir-boosted comparator PIin treatment-experienced patients with documented PI resistance. Allpatients received baseline genotype testing prior to randomization toaid investigators in the selection of the comparator PI.

Patients enrolled in RESIST-2 were randomized to receive anoptimized standard of care regimen containing tipranavir/r500mg/200mg twice daily or a CPI/r at its standard dose. CPIsincluded lopinavir, saquinavir, amprenavir and indinavir. Optimizedbackground regimens were chosen by patients' physicians on the basisof treatment history and baseline genotypic resistance testing. Theuse of enfuvirtide was allowed, but had to be pre-selected byinvestigators prior to randomization.

Tipranavir

Tipranavir is a non-peptidic protease inhibitor currently in PhaseIII of clinical development. In June 2004, Boehringer Ingelheimannounced the enrollment of the first patient in a broad-scale globaltipranavir Compassionate Use Program, which provides access toHIV-positive patients in clinical need of new treatment options.

Tipranavir is also being evaluated for use in pediatric andtreatment-naive patient populations. Phase II studies are currentlyunderway.

Based on available clinical and in vitro data, tipranavir isactive against most strains of HIV-1 that are resistant tocommercially available protease inhibitors. Ongoing studies aredesigned to confirm these data.

In studies to date, tipranavir has been well tolerated by mostpatients and has a safety profile similar to other PIs. The mostcommonly reported adverse events across all clinical trials weregastrointestinal-related and included diarrhea, nausea, fatigue,headache and vomiting. Consistent with other PIs, the most commonlaboratory abnormalities were elevated liver enzymes andtriglycerides.

Boehringer Ingelheim

Boehringer Ingelheim is committed to the research and developmentof novel antiretroviral agents. VIRAMUNE(R) (nevirapine) is a productof original research done at Boehringer Ingelheim. VIRAMUNE was thefirst member of the non-nucleoside reverse transcriptase inhibitor(NNRTI) class of anti-HIV drugs. Boehringer Ingelheim is committed tothe rapid development of the investigational non-peptidic proteaseinhibitor (NPPI) tipranavir in Phase III development and thenucleoside analogue (NRTI) alovudine in Phase II development. Thecompany is involved in basic research and is committed to improvingHIV therapy by providing physicians and patients with innovativeantiretrovirals.

For more information on Boehringer Ingelheim, please seehttp://www.boehringer-ingelheim.com/hiv .

Reference:

Cahn et al. 24-week data from RESIST 2: Phase 3 study of theefficacy and safety of either tipranavir/ritonavir (TPV/r) or anoptimized ritonavir (RTV)-boosted standard-of-care (SOC) comparatorPI (CPI) in a large randomized multicenter trial intreatment-experienced HIV+ patients. 7th International Congress onDrug Therapy in HIV Infection, Glasgow, UK, November 18, 2004.Abstract #: PL 14.3

Web site: http://www.boehringer-ingelheim.com http://www.boehringer-ingelheim.com/hiv

ots Originaltext: Boehringer IngelheimIm Internet recherchierbar: http://www.presseportal.de

Contact:Julia Meyer-Kleinmann, CD Communications, Boehringer Ingelheim GmbH, +49-61-32-77-8271, or fax +49-61-32-77-6601, or M-Kleinmann@ing.boehringer-ingelheim.com

Boehringer Ingelheim

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

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