FDA approves Symtuza for HIV-1.- Janssen Pharma.

Janssen Pharmaceutical announced the FDA has approved Symtuza (darunavir/cobicistat/emtricitabine/tenofovir alafenamide), the first and only complete, darunavir-based single-tablet regimen (STR) for the treatment of human immunodeficiency virus type 1 (HIV-1) in treatment-naïve and certain virologically suppressed adults. Symtuza combines the proven high barrier to resistance of darunavir with a formulation designed for improved tolerability and the convenience of an STR. Symtuza has a Boxed Warning regarding the risk of post-treatment acute exacerbation of hepatitis B.

Symtuza received FDA approval based on data from two 48-week, non-inferiority, pivotal Phase III studies that assessed the safety and efficacy of Symtuza versus a control regimen in adults with no prior ARV history (AMBER) and in virologically suppressed adults (EMERALD). Results from both trials demonstrated that Symtuza was effective and well-tolerated, with up to 95 percent achieving or maintaining virologic suppression (HIV-1 RNA less than 50c/mL).

AMBER compared Symtuza to darunavir/cobicistat (D/C) plus emtricitabine/tenofovir disoproxil fumarate (F/TDF). The results, presented at the 16th European AIDS Conference in October 2017, demonstrated similar viral suppression rates (HIV-1 RNA <50c/mL at 48 weeks – per FDA Snapshot analysis) between the darunavir-based STR vs. control (91.4% vs 88.4% respectively) and low virologic failure rates (HIV-1 RNA at least 50 c/mL; 4.4% vs. 3.3%) at 48 weeks. Symtuza also showed less bone loss (in a sub-study) and a significant improvement in markers of renal function versus control. The long-term clinical significance of these bone mineral density (BMD) changes is not known. Overall, Symtuza was well-tolerated, with fewer discontinuations due to an adverse event (AE; 2% vs. 4%) versus control, only one grade 3 adverse reaction and no grade 4 adverse reactions. The most frequent adverse reactions reported in at least 2% of subjects were diarrhea, rash, nausea, fatigue, headache, abdominal discomfort and flatulence.

The EMERALD study, presented at IDWeek in October 2017, compared Symtuza to continuing treatment with a boosted protease inhibitor (bPI) plus emtricitabine and TDF. The trial found there were low virologic failure rates (HIV-1 RNA at least 50 c/mL; 0.8% vs. 0.5%) and high virologic suppression rates (HIV-1 RNA less than 50 c/mL; 94.9% vs. 93.7%) according to FDA Snapshot analysis at Week 48, with no patients discontinuing the study due to virologic failure. Switching to Symtuza demonstrated improvement in BMD (in a sub-study) and a significant improvement in some markers of renal function versus control. The long-term clinical significance of these BMD changes is not known. The safety profile was similar to that of those patients with no prior ARV treatment history, and the percentage of participants who discontinued due to AEs, regardless of severity, was 1%.