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The Lancet Publishes 48-week Results From Tipranavir RESIST Studies in HIV-1 Infected Patients

INGELHEIM, GERMANY -- August 8, 2006 -- Data from a 48-week combined analysis of the RESIST-1 and RESIST-2 studies, which evaluated Aptivus® (tipranavir) in treatment-experienced HIV-1 infected patients, were reported today in The Lancet, and demonstrate that Aptivus® provides a convincing and durable benefit, achieving and maintaining a superior treatment response in treatment-experienced HIV-positive patients.

"The 48-week results from the tipranavir RESIST studies are encouraging for patients with virus that is resistant to multiple protease inhibitors. These data demonstrate that this patient population clearly benefits from the use of antiretroviral agents that remain active against resistant viruses. When used appropriately, tipranavir can be central to achieving durable HIV suppression and immunologic improvement," said Charles Hicks, M.D., Associate Professor of Medicine, Infectious Diseases and International Health, Duke University Medical Center, Durham, North Carolina.

A combined analysis of the RESIST-1 and RESIST-2 clinical trials demonstrated that Aptivus® continues to outperform a group of ritonavir-boosted comparator protease inhibitors (PIs) that included lopinavir/r (Kaletra®), amprenavir/r (Agenerase®), saquinavir/r (Invirase®) and indinavir/r (Crixivan®), through 48 weeks. In the RESIST studies, treatment response was defined as a confirmed 1 log10 or greater decrease in viral load from baseline.

When compared to these PIs:
· More than double the percentage of patients in the Aptivus® arm responded to treatment (33.6% vs. 15.3% achieved a treatment response) and were able to reduce the amount of HIV present in their blood (viral load) to undetectable levels (30.4% vs. 13.8% achieved a viral load of less than 50 copies/mL, p <.0001)
· Treatment with Aptivus® more than doubled the amount of patients' immune (CD4+) cells (mean CD4+ increases of +44.8 cells/mm³ vs. +21.1 cells/mm³)
· Enfuvirtide-naïve patients receiving enfuvirtide with Aptivus® achieved increases in treatment response to 58.5% vs. 21.6% of enfuvirtide-naïve patients receiving enfuvirtide with a comparator protease inhibitor

These findings demonstrate that treatment regimens containing Aptivus® as part of combination therapy may provide an active backbone for patients with drug resistant HIV-1 strains who have experienced triple-class treatment failure. Once patients experience triple-drug class virological failure, their treatment options are extremely limited and they are at increased risk of death.1

Aptivus® also showed higher efficacy when administered in patients with less advanced disease (low viral loads, high CD4+ counts):
· In patients with a baseline viral load of less than or equal to 10,000 copies/mL, 54.1% of patients receiving Aptivus® achieved a treatment response vs. 33.3% of patients receiving a comparator protease inhibitor
· In patients with a baseline viral load greater than 10,000 up to 100,000 copies/mL, 33.5% of patients receiving Aptivus® achieved a treatment response vs. 15.7% of patients receiving a comparator protease inhibitor
· In patients with a baseline viral load of greater than 100,000 copies/mL, 25.7% of patients receiving Aptivus® achieved a treatment response vs. 7.6% of patients receiving a comparator protease inhibitor
· In patients with baseline CD4+ cell counts greater than 350 cells/mm3, 41.3% (45/109) of patients receiving Aptivus® achieved a treatment response vs. 21.8% (27/124) of patients in the CPI/r group

Aptivus® Clinical Trial Program
Boehringer Ingelheim is actively conducting a clinical trial program to further evaluate Aptivus® for the treatment of HIV-1 infection. The Aptivus® clinical trial program is comprised of ongoing and planned studies in more than 1,000 treatment-experienced patients, including paediatric, racially and gender diverse, or hepatitis co-infected patients.

About RESIST
The RESIST trials are randomised, controlled, open-label, Phase III trials designed to study Aptivus® combined with ritonavir versus a group of ritonavir-boosted comparator protease inhibitors. The RESIST clinical trial program is one of the largest study programs undertaken with an investigational antiretroviral agent in patients previously treated with three classes of antiretrovirals, with Phase II and III data from more than 1,400 patients taking the 500 mg/200 mg dose of Aptivus/r. Ninety-six week data from RESIST-1 and RESIST-2 are expected later this year.

About Aptivus®
Aptivus® is a new non-peptidic protease inhibitor which works by inhibiting the viral protease, an enzyme needed to complete the HIV replication process. It is approved for combination antiretroviral treatment of HIV-1 infected adults that are highly pre-treated with virus resistant to multiple protease inhibitors.

Based on available clinical and in vitro data, Aptivus® is active against most strains of HIV-1 that are resistant to commercially available protease inhibitors. The safety and efficacy of Aptivus® in paediatric patients has not yet been established.

Currently, phase II and III studies in paediatric and other populations are fully enrolled and ongoing.

In studies to date, Aptivus® has been well tolerated by most patients and has a safety profile similar to other PIs. The most commonly reported side effects of at least moderate intensity in patients enrolled in the RESIST studies taking Aptivus® are gastrointestinal, including diarrhoea, nausea, vomiting and abdominal pain. Fever, fatigue, headache, bronchitis, depression and rash also occurred.

Aptivus® boosted with low-dose ritonavir has been associated with reports of hepatic adverse events, which have included some fatalities. Extra vigilance is warranted in patients with chronic hepatitis B or hepatitis C co-infection, as these patients have an increased risk of liver toxicity. The most common moderate to severe laboratory abnormalities were elevated liver enzymes and elevated lipid levels. Most laboratory abnormalities were asymptomatic and most patients were successfully treated without discontinuation.

Aptivus® does not cure HIV infection/AIDS or prevent the transmission of HIV to others. Patients may continue to develop opportunistic infections and other complications associated with HIV disease.

Apart from the EU, Aptivus® has received U.S. marketing authorization by the FDA and was launched there in June 2005. Additional marketing authorizations from different countries have been received or are expected.

REFERENCES:
1 Ledergerber B, Lundgren JD, Walker AS, et al. Predictors of trend in CD4-positive T-cell count and mortality among HIV-1-infected individuals with virological failure to all three antiretroviral-drug classes. Lancet 2004;364(9428):51-62.


SOURCE: Boehringer Ingelheim

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