General Information

Edurant (rilpivirine) is a diarylpyrimidine non-nucleoside reverse transcriptase inhibitor of human immunodeficiency virus type 1 (HIV-1) and inhibits HIV-1 replication by non-competitive inhibition of HIV-1 reverse transcriptase.

Edurant is specifically approved in combination with other antiretroviral agents for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in treatment-naïve patients 12 years of age and older and weighing at least 35 kg with HIV-1 RNA less than or equal to 100,000 copies/mL.

Edurant is supplied as a tablet for oral administration. The recommended dose is one 25 mg tablet once daily taken orally with a meal. See drug label for specific dosing recommendations by age and with other treatments.

Clinical Trial Results

The FDA approval of Edurant was based on 48-week data from two randomized, double-blinded, active controlled trials TMC278-C209 (ECHO) and TMC278-C215 (THRIVE) and from a 96-week randomized, active-controlled, dose-comparison phase IIb trial. The phase III trials were identical in design, with the exception of the background regimen.
TMC278-C209 (ECHO)
This double-blind, randomized study (Efficacy Comparison in treatment-naive HIV-infected subjects Of TMC278 and EFV) enrolled 680 subjects across several international sites. The subjects received TMC278 (25 mg) as a once daily oral tablet or efavirenz (EFV) (600 mg) once daily, each combined with a fixed background regimen consisting of emtricitabine plus tenofovir disoproxil fumarate.
TMC278-C215 (THRIVE)
This double-blind randomized study (TMC278 against HIV, in a once daily RegImen Versus Efavirenz) enrolled 680 subjects across several international sites. The subjects received TMC278 (25 mg) once daily or EFV (600 mg) once daily, both combined with an investigator-selected background regimen consisting of two N[t]RTIs (abacavir + lamivudine or tenofovir disoproxil fumarate + emtricitabine or zidovudine + lamivudine).
Pooled Results
Both trials reached their primary objective, the non-inferiority of TMC278 vs. EFV in the proportion of patients achieving an undetectable viral load (less than 50 copies/mL) at week 48 (with a maximum allowable difference of 12%). Results showed that 84.3% of patients in the TMC278 group reached an undetectable viral load, compared with 82.3% of patients in the EFV group. The virologic failure rate was 9% in the TMC278 group and 4.8% in the EFV group.
Study TMC278-C204
This phase IIb randomized, active-controlled trial enrolled 368 HIV-1-infected treatment-naïve adults. It consisted of two parts: an initial 96 weeks, partially-blinded dose-finding part followed by a long-term, open-label part. After Week 96, subjects randomized to one of the thrree doses of Edurant were switched to Edurant 25 mg once daily. Subjects in the control arm received efavirenz 600 mg once daily in addition to a background regimen in both parts of the study. At 96 weeks, the proportion of subjects with <50 HIV-1 RNA copies/ml receiving Edurant 25 mg (N = 93) compared to subjects receiving efavirenz (N = 89) was 76% and 71%, respectively. The mean increase from baseline in CD4+ counts was 146 x 106 cells/mm3 in subjects receiving Edurant 25 mg and 160 x 106 cells/mm3 in subjects receiving efavirenz. At 192 weeks, 63% (59/93) of subjects who originally received 25 mg once daily achieved HIV RNA < 50 copies/mL compared to 61% (54/89) of subjects in the control group.