Phase 3b ODIN study of once-daily PREZISTA in HIV-1 adults presented at CROI 2010

In a new study of treatment-experienced HIV-1-infected adults with no PREZISTA® (darunavir) resistance-associated mutations (RAMs), 72 percent of patients in the PREZISTA/ritonavir (r) (800/100 mg) once-daily arm achieved undetectable viral loads (<50 copies/mL) compared with 71 percent of patients in the PREZISTA/r (600/100 mg) twice-daily arm. The study met its primary objective of non-inferiority.  These data from the Phase 3b ODIN study were presented today at CROI 2010, the 17th Conference on Retroviruses and Opportunistic Infections, in San Francisco.  

Once-daily PREZISTA/r is an investigational regimen for treatment-experienced adult patients.  The current FDA-approved dosing recommendation is PREZISTA/r 800/100 mg once daily for treatment-naive adults (patients starting treatment for the first time) and PREZISTA/r 600/100 twice daily for treatment-experienced adults (patients who have taken HIV medications in the past), in combination with other antiretrovirals and with food. Tibotec plans to file data supporting the use of once-daily dosing for treatment-experienced adults from the ODIN (Once-daily Darunavir In treatment-experieNced patients) study with the U.S. Food and Drug Administration, the European Medicines Agency (EMEA) and other national regulatory agencies for approval.

"It is our hope that with FDA approval, PREZISTA once-daily dosing will provide an important option for treatment-experienced patients with no PREZISTA resistance-associated mutations, which represents a large percentage of the treatment-experienced population," said Ron Falcon, vice president, Tibotec Therapeutics Clinical Affairs.  

In the ODIN study, 590 patients were randomized to receive treatment with either PREZISTA/r 800/100 mg once daily or PREZISTA/r 600/100 mg twice daily. For both treatment arms, PREZISTA/r was used in combination with an optimized background regimen (OBR) of at least two nucleoside reverse transcriptase inhibitors (NRTIs). Overall, 46 percent of patients were protease inhibitor (PI)-naive and 13 percent were non-nucleoside reverse transcriptase inhibitor (NNRTI)-naive; 86 percent were susceptible to eight PIs (excluding ritonavir) and 60 percent were susceptible to at least two NRTIs in their OBR. At 48 weeks, a similar proportion of patients in both treatment arms achieved an undetectable viral load of <50 copies/mL (72 percent once-daily vs. 71 percent twice-daily). The study met its primary objective of non-inferiority.

The incidence of serious adverse events in the study was 5.4 percent in the once-daily group vs. 9.1 percent in the twice-daily group.  The incidence of grade 2 to 4 adverse events was 3.7 percent vs. 4.4 percent for nausea, 3.7 percent vs. 3.7 percent for diarrhea and 2.4 percent vs. 3.0 percent for vomiting, respectively. The incidence of grade 2 to 4 lipid and liver abnormalities with once-daily treatment vs. twice-daily treatment was 5.2 percent vs. 11.0 percent for triglycerides, 10.1 percent vs. 20.6 percent for total cholesterol, 9.8 percent vs. 16.7 percent for LDL cholesterol, and 1.7 percent/2.1 percent vs. 3.5 percent/3.5 percent for ALT/AST.