Efficacy of Investigational Anti-HIV Agent Tipranavir Demonstrated by New Data
INGELHEIM, Germany,, February 28 (ots/PRNewswire)
- Tipranavir/r More Effective Than Lopinavir/r in Large-Scale Studies of Treatment-Experienced HIV-Positive Patients
New data from multiple analyses presented last week at the 12th Conference on Retroviruses and Opportunistic Infections support the efficacy of the investigational non-peptidic protease inhibitor tipranavir in treatment-experienced HIV-positive patients. In a 24-week analysis of the RESIST pivotal Phase III studies, treatment regimens containing tipranavir boosted with low-dose ritonavir (tipranavir/r) were more effective than regimens containing lopinavir, the market leading protease inhibitor (PI) that is boosted with low-dose ritonavir (lopinavir/r or Kaletra(R)). In another recent 24-week analysis, tipranavir-containing regimens were consistently more effective than regimens containing a comparator PI of lopinavir, saquinavir, amprenavir or indinavir, regardless of the number and type of baseline protease mutations. These analyses also indicate that more patients achieved a treatment response whenever other active anti-HIV agents were added to tipranavir therapy.
"The RESIST data illustrate that tipranavir is an effective anti-HIV agent that may offer a new treatment for a wide range of treatment-experienced patients," stated Dr. David Cooper, Director of the National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia.
Efficacy of Tipranavir/r vs. Lopinavir/r (1)
In the RESIST studies, treatment response was defined as a confirmed 1 log(10) drop in viral load at 24 weeks. Treatment response was achieved by 39.6% of patients who received tipranavir/r therapy compared to 21.4% of patients who received lopinavir/r (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 lopinavir/r. At 24 weeks, 34.1% of patients in the tipranavir/r arm and 18.3% in the lopinavir/r arm achieved a viral load of less than 400 copies/mL. Patients treated with tipranavir/r also experienced a greater increase in CD4+ cell count than those treated with lopinavir/r, with CD4+ increases of 31 cells/mm3 vs. 6 cells/mm3, respectively.
Addition of Active Anti-HIV Agents (1)
A separate analysis showed that the use of more active anti-HIV agents in patients' optimized background regimen (OBR) increased treatment response in both the tipranavir/r and the comparator PI/r arms. A consistently greater proportion of patients in the tipranavir/r arm achieved a treatment response vs. the comparator PI/r arm with the addition of each active anti-HIV agent: 13.1% of patients in the tipranavir/r arm experienced a treatment response vs. 9.1% of patients in the comparator PI/r arm when no additional active anti-HIV agents were included in patients' OBR; 37.4% vs. 12.9% of patients experienced a treatment response with one additional active agent; 46.2% vs. 19.9% with two additional agents; and 54.7% vs. 34.3% with three or more additional agents.
Impact of Baseline Protease Mutations on Response to Tipranavir (2)
An additional analysis of the RESIST data shows that a consistently greater proportion of patients taking tipranavir/r responded to treatment than patients taking a comparator PI/r, regardless of the number and type of baseline protease mutations.
Treatment response was achieved by 50.4% vs. 29.8% of patients with 12 or fewer protease gene mutations in the tipranavir/r and comparator PI/r arms, respectively. In the presence of 19 or more mutations, 31.7% of patients taking tipranavir/r vs. 7.7% of patients taking a comparator PI/r achieved a treatment response.
The number of primary PI mutations did not affect response to tipranavir therapy. In patients with up to six primary PI mutations, more than 40% in the tipranavir/r arm responded to treatment. In the comparator PI/r arm, treatment response varied based on the total number of primary PI mutations present -- 28% of patients with 1-2 mutations, 13.6% with 3-4 mutations, and 16.7% with 5-6 mutations achieved a treatment response.
RESIST 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-1 and RESIST-2 are randomized, controlled, open-label Phase III trials 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.
Patients enrolled in the RESIST studies were randomized to receive an optimized standard of care regimen containing tipranavir/r 500mg/200mg twice daily or a comparator PI/r at its standard dose. All patients received baseline genotype testing prior to randomization to aid investigators in the selection of the comparator PI. Comparator PIs included lopinavir, saquinavir, amprenavir and indinavir; however, lopinavir was selected for 50% of patients in the comparator PI arm.
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 selected by investigators prior to randomization.
Tipranavir
Tipranavir is a non-peptidic protease inhibitor currently in Phase III of clinical development for use in treatment-experienced patients. Tipranavir is also being evaluated for use in pediatric and treatment-naïve patient populations.
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. These findings are currently being further evaluated in ongoing studies.
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. Patients treated with tipranavir experienced a higher rate of liver enzyme and lipid elevations; however, most laboratory abnormalities were asymptomatic and most patients were successfully treated without discontinuation.
Boehringer Ingelheim
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.
References:
(1) Cooper et al. 24-Week RESIST Study Analyses: the efficacy of
tipranavir/ritonavir (TPV/r) is superior to lopinavir/ritonavir
(LPV/r), and the TPV/r treatment response is enhanced by inclusion of
genotypically active antiretrovirals in the optimized background
regimen (OBR). 12th Conference on Retroviruses and Opportunistic
Infections, February 22-25, 2005, Boston, MA. Abstract #: 560.
(2) Schapiro et al. Impact of baseline genotype on response to
tipranavir/ritonavir (TPV/r) compared with standard-of-care comparator
PI (CPI/r) in treatment-experienced patients: results from the phase 3
RESIST-1 and RESIST-2 trials. 12th Conference on Retroviruses and
Opportunistic Infections, February 22-25, 2005, Boston, MA.
Abstract #: 104.INGELHEIM, Germany,, February 28 /PRNewswire/ --
Web site: http://www.boehringer-ingelheim.com/hiv
Contact:
Judith von Gordon, External Communications, Boehringer Ingelheim
GmbH, +49-61-32-77-3582, fax: +49-61-32-77-6601,
Judith.von.Gordon@ing.boehringer-ingelheim.com