FDA recommends approval of the investigational anti-HIV drug tipranavir

Boehringer Ingelheim today announced that the U.S. Food and Drug Administration's (FDA) Antiviral Drugs Advisory Committee recommended the approval of the investigational anti-HIV drug tipranavir (11-3). Tipranavir is a non-peptidic protease inhibitor that requires boosting with low-dose ritonavir and must be used in combination with other antiretroviral agents.

"We are pleased with the committee's recommendation and commend its thorough discussion of the tipranavir clinical data," said Dr. Andreas Barner, Member of the Board of Managing Directors of Boehringer Ingelheim, responsible for Research, Development and Medicine. "We look forward to soon being able to offer patients in need a new, efficacious treatment alternative."

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.

The committee's recommendations will be considered by the FDA in its review of the New Drug Application that Boehringer Ingelheim submitted for tipranavir. The FDA is not bound by the committee's recommendation, but takes its advice into consideration when reviewing investigational drugs seeking approval.

Boehringer Ingelheim will continue to provide tipranavir 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.

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/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-naive patient populations in Phase 2 and 3 studies that are currently underway.

The most commonly (greater than or equal to 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 (greater than or equal to 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.

Tipranavir does not cure HIV infection/AIDS or prevent the transmission of HIV to others. There are no study results demonstrating the effects of tipranavir on the clinical progression of HIV.