FDA Antiviral Drugs Advisory Committee Recommends Accelerated Approval for Experimental Protease Inhibitor Tipranavir (Aptivus)

Boehringer Ingelheim Pharmaceuticals, Inc. announced today that the US Food and Drug Administration’s (FDA) Antiviral Drugs Advisory Committee has recommended approval of the company’s experimental HIV protease inhibitor tipranavir (Aptivus). Although the FDA is not bound to accept the recommendations of its advisory committees, it almost always does.

Tipranavir is a non-peptidic protease inhibitor that requires “boosting” with low-dose ritonavir (Norvir) and must be used in combination with other antiretroviral agents.

Following are excerpts for the text of the company’s announcement about today’s recommendation of approval for tipranavir:

“We are pleased with the committee’s recommendation and commend its thorough discussion of the tipranavir clinical data,” said Burkhard Blank, M.D., Senior Vice President, Medical and Drug Regulatory Affairs, Boehringer Ingelheim Pharmaceuticals, Inc.  “We look forward to working with the FDA on the comments raised by the Advisory Committee and on the next steps of the application review process.”

The committee's positive recommendation is based on data from two large, well-controlled Phase 3 clinical trials, RESIST-1 and RESIST-2, conducted in protease inhibitor (PI)-resistant treatment-experienced patients.  These patients had taken three classes of anti-HIV drugs and were failing their PI-based regimen at the time of study entry.  These trials examine the treatment response of tipranavir boosted with ritonavir (TPV/r) versus a comparator group in which patients received one of several marketed ritonavir-boosted PIs.  In addition, patients in both arms received an optimized background regimen of other antiretroviral drugs.

Following the expected official approval of tipranavir, Boehringer Ingelheim will continue to provide the drug to eligible patients prior to its commercial availability through a Compassionate Use Program, which is being run as an Expanded Access Program in the U.S.

About Tipranavir

Tipranavir is a non-peptidic protease inhibitor currently in late Phase 3 clinical development.  Boehringer Ingelheim submitted a New Drug Application for tipranavir to the U.S. Food and Drug Administration in late 2004 that was granted a priority, six-month review in February 2005. 

Based on available clinical and in vitro data, tipranavir/ritonavir (tipranavir/r) appears to retain activity against many strains of HIV-1 that are resistant to commercially available protease inhibitors.  These findings are currently being further evaluated in ongoing studies.  Tipranavir/r is also being evaluated for use in pediatric and treatment-naïve patient populations in Phase 2 and 3 studies that are currently underway.

The most commonly (≥ 1%) reported adverse events in patients across all tipranavir clinical trials to date are gastrointestinal, including diarrhea, nausea and vomiting, as well as fatigue and headache.  Mild rash occurred more often in women than in men.  The most common (≥ 2%) grade 3/4 laboratory abnormalities in patients are elevated liver enzymes and lipids.  Patients treated with tipranavir/r experienced a significantly higher rate of liver enzyme and lipid elevations; however, most laboratory abnormalities were asymptomatic and most patients were successfully treated without discontinuation. 

Tipranavir co-administered with low-dose ritonavir has been associated with reports of clinical hepatitis and hepatic decompensation, including some fatalities.  These have generally occurred in patients with advanced HIV disease taking multiple concomitant medications. A causal relationship to tipranavir could not be established. 

Ongoing studies will continue to evaluate the safety and efficacy of tipranavir/r. There are no study results demonstrating the effects of tipranavir on the clinical progression of HIV.

Tipranavir does not cure HIV infection/AIDS or prevent the transmission of HIV to others. 

About Boehringer Ingelheim

Boehringer Ingelheim is committed to the research and development of novel antiretroviral agents.  VIRAMUNE (nevirapine), a product of original research done at Boehringer Ingelheim, was the first member of the non-nucleoside reverse transcriptase inhibitor (NNRTI) class of anti-HIV drugs.  Boehringer Ingelheim is involved in basic research and is committed to the development of tipranavir and improving HIV therapy by providing physicians and patients with innovative antiretrovirals.

For more information on Boehringer Ingelheim, please visit http://us.boehringer-ingelheim.com.

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