By Liz Highleyman

Tibotec's investigational next-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine (TMC278) has previously demonstrated good efficacy and tolerability in an international Phase 2b trial of treatment-naive patients through 48 weeks.

Investigators presented 96-week follow-up data at the XVII International Conference on AIDS taking place this week in Mexico City.

In this trial (TMC278-C204), 368 patients (one-third of whom were women) were randomly assigned to receive rilpivirine at one of 3 blinded once-daily doses (25 mg, 75 mg, or 150 mg), or else 600 mg open-label efavirenz (Sustiva), as part of a combination antiretroviral regimen that included 2 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs); 76% received zidovudine (AZT; Retrovir) + lamivudine (3TC; Epivir), while 24% took tenofovir (Viread) + emtricitabine (Emtriva).

Results

• In a time to loss of virological response (TLOVR) analysis, 76% of patients in the rilpivirine 25 mg arm, 72% in the 75 mg arm, and 71% in the 150 mg arm (73% for all rilpivirine arms combined) achieved HIV RNA < 50 copies/mL, compared with 71% in the efavirenz arm.

• Mean CD4 cell increases were 146, 172, and 159 cells/mm3 in the respective rilpivirine dose groups, compared with 160 cells/mm3 in the efavirenz group.

• Only 1 patient in the rilpivirine arms and 2 in the efavirenz arm discontinued treatment between 48 and 96 weeks.

• Overall, patients in the rilpivirine combined group (all doses) and the efavirenz group experienced similar frequencies and types of serious adverse events (SAEs), 12% vs 15%, respectively.

• Rates of grade 3 or 4 adverse events (AEs) were 27% and 21%, respectively.

• Rates of grade 3 or 4 laboratory abnormalities were 27% and 24%, respectively.

• Participants taking rilpivirine were less likely than those taking efavirenz to experience rash (9% vs 21%), central nervous system AEs (31% vs 48%), and psychiatric events (16% vs 21%).

• Triglyceride levels fell by about 10 mg/dL in the rilpivirine arm, compared with a 29 mg/dL rise in the efavirenz group.

Based on these findings, the investigators concluded that "TMC278 [rilpivirine] was generally well tolerated with less increase in serum lipids and lower incidences of rash, nervous system and psychiatric events, compared with efavirenz."

They added that "TMC278 demonstrated a high response rate and sustained virologic response over 96 weeks."

"NNRTIs have been an integral part of combination antiretroviral therapy for over a decade," investigator Peter Shalit, MD, of Swedish Medical Center in Seattle said in a press release issued by Tibotec. "[These] Phase IIb data show potential for rilpivirine as a once-daily treatment option for patients who have not previously taken anti-HIV medications."

Tibotec has started enrollment and is recruiting treatment-naive patients for 2 large Phase 3 trials of rilpivirine, using the 25 mg dose, in Africa, Asia, Europe, North America, and South America.

Hospital Carlos Mac Gregor IMSS, Mexico City, Mexico; Hospital Juan A Fernández and Fundación Huesped, Buenos Aires, Argentina; Hospital das Clíncias, Pinheiros, Brazil; Beijing You'an Hospital, Beijing, China; Chelsea and Westminster NHS Foundation Trust and PKR/SSR, London, UK; Swedish Medical Center, Seattle, WA; Tibotec BVBA, Mechelen, Belgium; Tibotec Inc, Yardley, PA.

8/08/08

Sources

M Santoscoy, P Cahn, C Gonsalez, and others. TMC278 (rilpivirine), a next-generation NNRTI, demonstrates long-term efficacy and tolerability in ARV-naive patients: 96-week results of study C204. XVII International Conference on AIDS (AIDS 2008). Mexico City. August 3-8, 2008. Abstract TUAB0103. (Abstract)

Tibotec Therapeutics. Ninety-six Week Data on Tibotec Investigational NNRTI, TMC278, Presented at AIDS 2008. Press Release. August 5, 2009.