Troy Brown, RN
July 18, 2018
The US Food and Drug Administration (FDA) has approved what its manufacturer calls "the first and only complete, darunavir-based single-tablet regimen (STR) for the treatment of human immunodeficiency virus type 1 (HIV-1) in treatment-naive and certain virologically suppressed adults." Using the brand name Symtuza and made by Janssen Pharmaceuticals, the drug combo "combines the proven high barrier to resistance of darunavir with a formulation designed for improved tolerability and the convenience of an STR."
The combination tablet contains darunavir 800 mg, cobicistat 150 mg, emtricitabine 200 mg, and tenofovir alafenamide 10 mg. The once-daily STR is expected to improve patient compliance, which will also help prevent drug resistance.
"The approval of Symtuza…will provide patients with yet another one-tablet regimen with excellent potency, tolerability, and a high genetic barrier to resistance," Antonio Urbina, MD, associate professor of infectious diseases at the Icahn School of Medicine at Mount Sinai in New York City, told Medscape Medical News.
"At the Institute for Advanced Medicine at Mount Sinai, it will become one of our antiviral options for our immediate start program, which provides same-day HIV treatment to patients newly diagnosed with HIV," he added.
Urbina said there are currently eight other one-tablet regimens for HIV, but they "do not include a protease inhibitor [such as darunavir]. The use of a protease inhibitor-based regimen may be preferable in certain patient populations, for example, patients with suboptimal adherence," Urbina explained.
Effective, Well-tolerated in Pivotal Trials
The FDA approval follows consideration of data from two 48-week, noninferiority, pivotal phase 3 studies that compared the drug's safety and efficacy with those of a control regimen in two different populations of patients with HIV-1 infection.
The AMBER study included antiretroviral-naive adults and the EMERALD study included virologically suppressed adults. The drug combo was effective and well-tolerated in both studies, and as many as 95% of patients in the treatment groups achieved or maintained virologic suppression, defined as HIV-1 RNA less than 50 copies/mL.
The AMBER study compared the darunavir-based STR with darunavir/cobicistat plus emtricitabine/tenofovir disoproxil fumarate (F/TDF). Viral suppression rates (HIV-1 RNA 50 copies/mL at 48 weeks, per FDA Snapshot analysis) were similar between the darunavir-based STR and control groups (91.4% vs 88.4%, respectively) and virologic failure rates were low (HIV-1 RNA = 50 c/mL; 4.4% vs 3.3%) at 48 weeks.
The darunavir-based combo was associated with less bone loss than the control treatment during a substudy, although the long-term clinical significance of this finding is unclear. Renal function markers were also significantly improved compared with the control group.
Fewer patients in the darunavir-based treatment group withdrew from the study as a result of adverse events (AEs) than in the control group (AE, 2% vs 4%). Only one grade 3 adverse reaction and no grade 4 adverse reactions occurred. The most common adverse reactions that occurred in at least 2% of participants were diarrhea, rash, nausea, fatigue, headache, abdominal pain, and flatulence.
The AMBER study results were presented at the 16th European AIDS Conference in October 2017.
In the EMERALD study, researchers compared the darunavir-based treatment with continuing treatment with a boosted protease inhibitor plus emtricitabine and TDF. Virologic failure rates (HIV-1 RNA = 50 copies/mL; 0.8% vs 0.5%) were low and virologic suppression rates were high (HIV-1 RNA 50 copies/mL; 94.9% vs 93.7%) according to FDA Snapshot analysis at week 48.
No patients discontinued the study as a result of virologic failure. Those who switched to the darunavir-based treatment experienced improved bone mineral density in a substudy and significantly improved renal function markers; however, the long-term clinical significance of the bone mineral density changes is unclear.
Patients in the EMERALD study experienced few AEs in a similar manner as patients who were naïve to antiretroviral therapy, with only 1% discontinuing treatment as a result. Results from the EMERALD Study were presented at ID Week in October 2017.
The drug label will contain a boxed warning about the risk for posttreatment acute exacerbation of hepatitis B infection.
Before beginning treatment, patients should undergo testing for hepatitis B infection and renal function, with continued monitoring of renal function during treatment. Symtuza should not be given to patients whose creatinine clearance is lower than 30 mL per minute or who have severe renal impairment.
The European Medicines Agency's (EMA's) Committee for Medicinal Products for Human Use recommended the combination therapy for marketing approval on July 21, 2017, and the EMA approved it on September 26, 2017.
Urbina has disclosed that he is on the scientific advisory panels for Gilead, Merck, and ViiV.