Janssen Pharmaceutical today unveiled 96-week results from the pivotal Phase 3 AMBER study of Symtuza (darunavir 800 mg, cobicistat 150 mg, emtricitabine 200 mg and tenofovir alafenamide 10 mg (D/C/F/TAF)) at HIV Glasgow in Scotland. D/C/F/TAF is a once-daily darunavir-based single-tablet regimen (STR), for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults and adolescents aged 12 years and older with body weight of at least 40 kg. Genotypic testing should guide the use of D/C/F/TAF.
Results from the AMBER study demonstrated that a high proportion of antiretroviral treatment (ART)-naïve adults with HIV-1 (85%, 308/362) maintained virologic suppression (viral load <50c/mL; FDA-snapshot) at 96 weeks when treated with D/C/F/TAF. No darunavir, primary protease inhibitor, or tenofovir resistance-associated mutations emerged in any patient. As previously reported, only one patient receiving D/C/F/TAF developed a nucleoside reverse transcriptase inhibitor resistance-associated mutation (M184V) through week 48. In the current analysis through 96 weeks, only one additional patient receiving D/C/F/TAF developed a nucleoside reverse transcriptase inhibitor resistance-associated mutation to emtricitabine (M184V).
“The 96-week results from the AMBER study demonstrate that the darunavir-based single-tablet regimen has a good safety profile and efficacy and a high genetic barrier beyond the first year of treatment. The regimen adds to the choices for patients who start and receive life-long HIV therapy,” said Professor Chloe Orkin, Lead for HIV research at Barts Health NHS Trust.
On September 26, 2017, D/C/F/TAF was approved for the treatment of HIV-1 infection by the European Commission, based on results from a bioequivalence study that compared D/C/F/TAF with the combined administration of the separate agents darunavir [D] 800 mg, cobicistat [C] 150 mg, and emtricitabine/tenofovir alafenamide [FTC/TAF] 200 mg/10 mg fixed-dose combination. US FDA approval was granted on July 17, 2018 based on the results from the two pivotal Phase 3 studies, EMERALD and AMBER.
D/C/F/TAF is a fixed-dose combination of four active substances (darunavir, cobicistat, emtricitabine and tenofovir alafenamide), available as 800 mg/150 mg/200 mg/10 mg film-coated tablets. Darunavir inhibits the HIV protease and prevents the formation of mature infectious virus particles. Emtricitabine and tenofovir alafenamide are substrates and competitive inhibitors of HIV reverse transcriptase. After phosphorylation, they are incorporated into the viral DNA chain, resulting in chain termination. Cobicistat enhances the systemic exposure of darunavir and has no direct antiviral effect.