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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

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