Phase III EMERALD study of Symtuza (darunavir + cobicistat + emtricitabine + tenofovir alafenamide) in HIV published in The Lancet HIV.- Janssen Pharma.

Janssen Pharmaceutica announced results from the pivotal Phase III EMERALD study of Symtuza (darunavir + cobicistat + emtricitabine + tenofovir alafenamide) in HIV patients which were published online in The Lancet HIV. The study met its primary endpoint, which focused on virologic rebound rate, and demonstrated that switching to the investigational single-tablet regimen (STR) containing darunavir 800 mg, cobicistat 150 mg, emtricitabine 200 mg and tenofovir alafenamide 10 mg (D/C/F/TAF) was non-inferior to continuing treatment with a boosted protease inhibitor (PI) plus emtricitabine and tenofovir disoproxil fumarate in human immunodeficiency virus type 1 (HIV-1) positive, virologically suppressed adults. There were no observed resistance associated mutations (RAMs) to study drugs through 48 weeks.

Through 48 weeks, cumulative virologic rebound was 2.5% (D/C/F/TAF, n=19) vs. 2.1% (control, n=8) with 12/19 in D/C/F/TAF and 4/8 in the control group re-suppressed (<50 c/mL) by the end of the evaluation period. Additionally, at week 48, virologic suppression was 94.9% (D/C/F/TAF) and 93.7% (control), and virologic failure occurred in 0.8% and 0.5%, respectively, with no discontinuations for virologic failure and no observed RAMs to any study drug through 48 weeks.

D/C/F/TAF also demonstrated similar safety versus control group through 48 weeks. Rates of discontinuations due to adverse events (AEs) were 1.4% (D/C/F/TAF) vs. 1.3% (control); Grade 3-4 AEs were 6.8% (D/C/F/TAF) vs. 8.2% (control); and serious AEs were 4.6% (D/C/F/TAF) vs. 4.8% (control). There were no deaths in either arm of the study. The most common AEs were nasopharyngitis (D/C/F/TAF 10.6% vs. control 10.3%), upper respiratory tract infection (10.6% vs. 10.3%), and diarrhea (7.9% vs. 4.2%). If approved in the U.S., D/C/F/TAF would be the only complete regimen that may deliver the potential adherence benefit of a once-daily STR with the durability and high genetic barrier to resistance of darunavir and the demonstrated bone and renal safety profile of TAF. Data will be presented at IDWeek 2017 in San Diego.

See:"Efficacy and safety of switching from boosted protease inhibitors plus emtricitabine and tenofovir disoproxil fumarate regimens to single-tablet darunavir, cobicistat, emtricitabine, and tenofovir alafenamide at 48 weeks in adults with virologically suppressed HIV-1 (EMERALD): a phase 3, randomised, non-inferiority trial." Chloe Orkin et al. The Lancet HIV, Published: 06 October 2017, DOI: http://dx.doi.org/10.1016/S2352-3018(17)30179-0

Comment: On September 25, 2017, the European Commission approved the use of D/C/F/TAF for the treatment of HIV-1 infection in adults and adolescents aged 12 years and older with body weight of at least 40 kg. A new drug application (NDA) was filed on September 22, 2017 to the U.S. Food and Drug Administration (FDA), and is currently awaiting approval.