August 15, 2006 (AIDSmeds)—Additional results from two ongoing clinical trials of Prezista™
(darunavir), Tibotec, Inc.’s protease inhibitor approved by the U.S.
Food and Drug Administration (FDA) in June, suggest that the drug
offers prolonged treatment effects for HIV-positive people with limited
treatment options. The new data, reflecting 48 weeks of follow up from
the clinical trials, were reported today at the XVI International AIDS
Conference (IAC) in Toronto.
Prezista was approved by
the FDA based largely on early results from two phase IIb clinical
trials called POWER 1 and POWER 2. The two studies enrolled 588
HIV-positive people who had previously been treated with at least one protease inhibitor, one non-nucleoside reverse transcriptase inhibitor(NNRTI), and one nucleoside reverse transcriptase inhibitor (NRTI). Patients also needed have evidence, by way of drug-resistance testing, of one or more HIV mutation known to contribute to resistance to older protease inhibitor options.
The study participants were randomized to one of two groups. In the first group, 131 patients are taking Norvir®
(ritonavir)-boosted Prezista (600mg plus 100mg Norvir) twice daily plus
an optimized background regimen (OBR). In the second group – the
control group – 124 patients are taking an approved Norvir-boosted
protease inhibitor plus OBR.
Twenty-four week data
from both studies combined, which were reviewed by the FDA and used to
support accelerated approval of the drug, demonstrated that patients in
POWERs’ Prezista groups were more likely to achieve undetectable viral loads and experience increases in CD4 cell counts compared to control patients in the study.
After
24 weeks of follow up, 45% of patients in the Prezista groups had viral
loads below 50, compared to 12.1% of patients in the control groups.
The
combined 48-week data from the studies were reported at IAC by Sharon
Walmsley, MD, a POWER researcher and Senior Scientist at the Toronto
General Research Institute. She reported data involving 110 patients
who had reached 48 weeks of treatment in the Prezista groups and 120
patients who reached 48 weeks of treatment in the control groups.
According
to Dr. Walmsley, 61% of patients taking a Prezista-based regimen had
viral loads that were at least 1 log below their pre-study levels. In
the control groups, only 15% had a similar viral load response after 48
weeks of treatment. As for undetectable viral loads, 46% of the
Prezista-treated patients had viral loads below 50 after 48 weeks,
compared to 10% of the control patients.
Encouraging
CD4 count data were reported as well. After almost a year of treatment,
Prezista-treated patients experienced, on average, a 102-cell increase,
compared to an approximate 19-cell increase in the control groups.
Thus far, the most common side effects in the Prezista-treated patients, compared to those in the control group, include diarrhea (20% in the Prezista group vs. 28% in the control group), nausea (18% vs. 13%), headache (15% vs. 20%), and fatigue (12% vs. 17%). Dr. Walmsley noted that while increases in cholesterol and triglycerides
have been noted in patients participating in the studies, these
increases do not appear to be any more common in the Prezista-treated
patients compared to those in the control groups.
The
POWER researchers plan to publish final data from POWER 1 and POWER 2
based on 96-week follow-up results. However, Dr. Walmsley and her group
will follow patients for a total of 144 weeks—approximately three years
of effectiveness and safety data.
