June 13, 2006

Aptivus Study Halted

June 13, 2005 (AIDSmeds)—A clinical trial of Aptivus® (tipranavir) has been discontinued due to limited effectiveness, along with earlier concerns of liver toxicities, in treatment-naive study volunteers receiving the drug. While Aptivus remains an approved option for treatment-experienced patients, the new study results and clinical trial closure will likely raise significant questions about the use of Aptivus in HIV-positive patients starting therapy for the first time.

Study 1182.33 was designed to evaluate the effectiveness and safety of Aptivus (500 mg twice daily) combined with one of two doses of Norvir® (ritonavir; 100 or 200 mg twice daily) compared to Kaletra® (lopinavir plus ritonavir; 400 mg plus 100 mg twice daily) in HIV-positive volunteers starting treatment for the first time. All patients selected their own nucleoside reverse transcriptase inhibitors to combine with Aptivus/Norvir or Kaletra.

To help keep levels of Aptivus high in the blood, which is very important for the drug to be effective, it is necessary to combine Aptivus with Norvir.

In February, Boehringer Ingelheim announced that it was discontinuing the study's evaluation of Aptivus plus 200 mg Norvir. After 48 weeks of treatment, patients in both Aptivus/Norvir groups and the Kaletra group had similar viral load responses to treatment. While safety in both Aptivus/Norvir study groups was generally similar to that in the Kaletra group, the rate of liver enzyme increases reported in patients receiving Aptivus plus 200mg Norvir – the dose currently used to treat HIV-positive people who have tried and failed other protease inhibitors in the past – was higher than in the other study groups.

Because of this less favorable benefit-risk profile, the study of Aptivus plus 200 mg Norvir twice-daily was discontinued. However, the manufacturer opted to continue studying Aptivus plus 100 mg Norvir compared to Kaletra.

The manufacturer recently conducted an analysis involving all patients enrolled in the study for 60 weeks. At that time point, more volunteers taking Aptivus plus 100 mg Norvir had detectable viral loads (above 50 copies/mL), compared to those in the Kaletra group. As a result, the study of Aptivus plus 100 mg Norvir was terminated as well.

While these study results suggest that Aptivus will not likely be a recommended protease inhibitor option for HIV-positive people starting therapy for the first time, the manufacturer claims that the benefit-risk profile for Aptivus plus Norvir has not changed for highly treatment-experienced patients.

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