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24-week results from Aptivus® (tipranavir) RESIST studies published in Clinical Infectious Diseases

Pressmeddelande   •   Nov 16, 2006 15:03 CET

For medical media, outside the US only
Ingelheim/Germany, 16 November, 2006 - Data from two 24-week analyses of the RESIST-1 and RESIST-2 studies, which evaluated Aptivus® (tipranavir) in treatment-experienced HIV-1 infected patients, were published in the 15 November issue of Clinical Infectious Diseases. Data demonstrate that at 24-weeks Aptivus, used with ritonavir (Aptivus/r) as part of combination antiretroviral therapy, achieved superior antiviral and immunological activity in treatment-experienced patients with multidrug-resistant HIV-1 infection.

These 24-week results are supported by long-term data from RESIST combined analyses, which show that Aptivus/r provides a durable treatment response through nearly two years (96 weeks) of therapy.

“Findings from the RESIST studies, which are comprised of more than 1,400 patients, are important because once patients experience triple-class virological failure, their treatment options are extremely limited. Data show Aptivus provides these patients with an effective therapeutic option and the potential for long term treatment success.” said Pedro Cahn, M.D., director, Fundación Huesped, Buenos Aires, Argentina.

At 24 weeks, Aptivus/r outperformed a group of ritonavir-boosted comparator protease inhibitors that include lopinavir/r (Kaletra®), amprenavir/r (Agenerase®), saquinavir/r (Invirase®), and indinavir/r (Crixivan®). 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 protease inhibitors:

* More than twice the percentage of patients in the Aptivus/r arm reduced the amount of HIV present in their blood (viral load) to undetectable levels (less than 50 copies/mL), p<0.0001.1
* The virologic benefits of an Aptivus-based regimen were enhanced by co-administration with other active antiretroviral agents (e.g., the fusion inhibitor enfuvirtide), p<0.0001.1
* Treatment with Aptivus/r more than doubled the amount of patients’ immune (CD4+) cells, p<0.001.1

With regard to safety, gastrointestinal symptom disorders and elevated transaminase, cholesterol and triglycerides were more frequent in the Aptivus arms than in the comparator-ritonavir arms but necessitated discontinuation of treatment in a minority of cases. The majority of Grade 3 or 4 ALT elevations were clinically asymptomatic and more that three quarters of the patients developing a Grade 3 or 4 ALT elevation continued treatment with Aptivus/r.1 Rates of leucopoenia and increased lipase concentrations were more frequent in the comparator-ritonavir arms.

Aptivus Clinical Trial Programme
Boehringer Ingelheim is actively conducting a clinical trial programme to further evaluate Aptivus for the treatment of HIV-1 infection. So far Aptivus has already been studied in more than 6,800 patients.

The Aptivus clinical trial programme is comprised of ongoing and planned studies in more than 1,400 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 were presented 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.

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. Gastrointestinal symptom disorders and elevated transaminase, cholesterol and triglycerides were more frequent in the Aptivus arm than in the comparator-ritonavir group but necessitated discontinuation of treatment in a minority of cases. Rates of leucopoenia and increased lipase concentrations were more frequent in the comparator-ritonavir arm.

Aptivus boosted with low-dose ritonavir has been associated with reports of hepatic adverse events, which have included some fatalities. These have generally occurred in patients with advanced HIV disease taking multiple concomitant medications. 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 boosted with low-dose ritonavir has been associated with reports of both fatal and non-fatal intracranial hemorrhage (ICH). Caution should be used when prescribing Aptivus/r in patients who may be at risk of increased bleeding or who are receiving medications known to increase the risk of bleeding.

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.

Boehringer Ingelheim
Boehringer Ingelheim is committed to the research and development of novel antiretroviral agents. Apart from Aptivus® (tipranavir), Viramune® (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 on the market. The company is involved in basic research in that area and is committed to improving HIV therapy by providing physicians and patients with innovative antiretroviral treatment options.

1Notes
In 24-week analyses of RESIST-1 and RESIST-2:

RESIST-1
When Aptivus/r was compared to lopinavir/r, amprenavir/r, saquinavir/r, and indinavir/r:

* 34.7% vs. 16.5% of patients achieved viral loads of less than 400 copies/mL, respectively (p<0.0001)
* 25.1% vs. 10.0% of patients achieved viral loads of less than 50 copies/mL, respectively (p<0.0001)
* 32.8% vs. 14.3% of patients achieved a viral load of less than 50 copies/mL when co-administered with enfuvirtide, respectively (p<0.0001)
* Patients achieved mean CD4+ increases of +54 vs. +24 cells/mm3, respectively (p<0.001).

With regard to safety:

17 of 21 patients receiving Aptivus/r with grade 3 or 4 liver function test results continued to receive treatment without permanent discontinuation.

RESIST-2
When Aptivus/r was compared to lopinavir/r, amprenavir/r, saquinavir/r, and indinavir/r:

* 33.6% vs. 13.1% of patients achieved viral loads of less than 400 copies/mL, respectively (p<0.0001)
* 22.5% vs. 8.6% of patients achieved viral loads of less than 50 copies/mL, respectively (p<0.0001)
* Patients achieved mean CD4+ increases of +51 vs. +18 cells/mm3, respectively (p<0.001).

With regard to safety:

* 16 of 22 patients receiving Aptivus/r with grade 3 or 4 elevated transaminase levels continued to receive treatment without permanent discontinuation.


Contact:
Boehringer Ingelheim GmbH
Judith von Gordon
55216 Ingelheim am Rhein
GERMANY
Phone: +49/6132/77 35 82
Fax: +49/6132/77 66 01