Janssen’s once-daily, single tablet combination therapy SYMTUZA (darunavir/cobicistat/emtricitabine/tenofovir alafenamide [D/C/F/TAF]) has shown to be both highly effective and well-tolerated in treating antiretroviral-naïve HIV-1 patients through 48 weeks in the pivotal phase 3 AMBER study.
Findings from the study demonstrated that the single tablet regimen (STR) D/C/F/TAF provided effective and durable viral suppression, meaning most patients achieved an undetectable viral load, whilst offering the high genetic barrier to resistance of darunavir, for ART-naïve HIV-1-infected patients.
“The AMBER study results show that the boosted darunavir-based STR which also contains F/TAF was a highly effective regimen with favourable kidney and bone safety laboratory parameters compared to F/TDF (emtricitabine/tenofovir disoproxil fumarate). It was very well-tolerated, and doses in a single daily tablet,” said Chloe Orkin, Chair of the British HIV Association (BHIVA) and Consultant Physician at the Royal London Hospital.
AMBER is a Phase 3 randomised double-blind non-inferiority international study designed to assess the efficacy and safety of D/C/F/TAF versus the control in HIV-1 positive treatment-naïve adult patients over 48 weeks. The control comprised two separate medications – a tablet of darunavir/ cobicistat (D/C) plus a tablet of emtricitabine/ tenofovir disoproxil fumarate (F/TDF). The primary endpoint was non-inferiority of the STR versus the control regarding the proportion of patients with a viral load (VL) of less than 50 copies per mL at 48 weeks (per FDA snapshot analysis). Reducing their viral load to an undetectable level is a key treatment goal for HIV patients, enabling their immune system to strengthen and leading to improved quality of life.
The single tablet D/C/F/TAF demonstrated durable non-inferiority versus the control group over 48 weeks (HIV RNA <50 c/ml 91.4% vs 88.4% respectively, difference 2.7%; 95% CI: −1.6 to 7.1) and also produced low virologic failure rates (VL≥50 c/mL; FDA-Snapshot: 4.4% (16/362) versus 3.3% (12/363)). The high efficacy results were consistent across different subgroups of patients. No treatment-emergent mutations related to darunavir, primary protease inhibitors or tenofovir (TFV) were observed. The STR showed improved bone and renal safety laboratory parameters, along with similar safety versus control through 48 weeks, in terms of rates of discontinuations due to adverse events (AEs – 1.9% vs. 4.4%), of Grade 3-4 AEs (5.2% vs 6.1%), and of serious AEs (4.7% vs. 5.8%). D/C/F/TAF also demonstrated a similar total cholesterol/HDL cholesterol ratio, with limited lipid changes.
D/C/F/TAF safety and efficacy were also demonstrated in the open label Phase 3 48-week EMERALD study, a switch trial amongst virologically suppressed ART experienced patients.
D/C/F/TAF is the first once-daily darunavir-based single-tablet regimen (STR), and recently received European Commission approval on 21 September 2017. In the U.S., D/C/F/TAF is an investigational product and has not been proven to be safe or efficacious. A new drug application (NDA) was filed on 22 September 2017 with the U.S. Food and Drug Administration (FDA) and is currently awaiting approval.
D/C/F/TAF has been developed by Janssen to provide HIV patients with a convenient once-daily, single tablet that provides highly effective viral suppression through the combined action of darunavir, cobicistat, emtricitabine and tenofovir alafenamide. Furthermore, the new STR comes with the high genetic barrier to viral resistance development provided by darunavir and the favourable renal and bone safety profile seen with tenofovir alafenamide.