FDA Approves the First Complete Darunavir-Based Single-Tablet Regimen for HIV

The US Food and Drug Administration (FDA) has approved the first and only complete, darunavir-based single-tablet regimen (STR) for the treatment of HIV in treatment-naïve and certain virologically suppressed adults. The drug, D/C/F/TAF (SYMTUZA), which has been developed by the Janssen Pharmaceutical Companies of Johnson & Johnson, combines the resistance of darunavir with the tolerability and convenience of an STR.

"As clinicians, we may not always have the full picture of a patient's health or their risk for developing resistance when making treatment decisions,” Joseph Eron, MD, professor of medicine, Director, Clinical Core, University of North Carolina Center for AIDS Research said in the announcement, “In key Phase 3 clinical trials, SYMTUZA successfully treated those who were starting therapy, as well as those who were stably suppressed on antiretroviral (ARV) therapy — including patients with more complex treatment histories or previous virologic failure – demonstrating its potential as an important new treatment option for a wide variety of patients."

The FDA based the approval on data from 2 phase 3 studies, AMBER and EMERALD that assessed the safety and efficacy of D/C/F/TAF compared with a control regimen in adult patients without prior antiretroviral therapy and in virologically suppressed adults, respectively.

In the AMBER trial, the drug was compared with darunavir/cobicistat plus emtricitabine/tenofovir disoproxil fumarate. Results demonstrated similar suppression rates between the darunavir-based STR and the control (91.4% vs 88.4%) and low virologic failure rates (HIV-1 RNA ≥50 c/mL; 4.4% vs. 3.3%) at 48 weeks. Overall, the drug was well tolerated with few discontinuations due to an adverse event (2% vs. 4%) versus control; only 1 grade 3 adverse reaction occurred, and there were no grade 4 adverse reactions reported. Adverse reactions reported in ≥2% of subjects included diarrhea, rash, nausea, fatigue, headache, abdominal discomfort, and flatulence.

In the EMERALD trial, the darunavir-based STR was compared with continuing treatment using a boosted protease inhibitor (bPI) plus emtricitabine and TDF. Results found low virologic failure rates (HIV-1 RNA ≥50 c/mL; 0.8% vs. 0.5%) and high virologic suppression rates (HIV-1 RNA <50 c/mL; 94.9% vs. 93.7%) at week 48, with no patients discontinuing due to virologic failure. In a switch to the darunavir-based STR, there was an improvement in BMD (in a sub-study) and a significant improvement in some markers of renal function versus the control. Additionally, the safety profile was similar to patients with no prior ARV treatment history, and only 1% of patients discontinued due to adverse events.

“Despite significant progress [in the field of HIV], clinical challenges remain in patients with diverse backgrounds that may have had problems with adherence in the past or [who are] at risk of drug resistance," lead investigator, Gregory D. Huhn, MD, an infectious disease specialist in the Cook County Health system in Chicago, Illinois, told Contagion^®, "I think the results here—the posthoc analysis, the data from EMERALD—speaks to the real-life experiences that providers confront in treating different patient populations that have had different levels of experience. D/C/F/TAF is in use in Europe, and if it is approved here [in the United States] it will offer a simplified, single-tablet regimen for providers to have at their disposal."

The recommended dose of the darunavir-based STR is 1 tablet to be taken daily with food. The drug is not recommended for patients with creatine clearance below 30mL per minute or those with severe hepatic impairment. Additionally, patients should be tested for hepatitis B virus infection and renal function should be monitored during therapy.

The darunavir-based STR has also been approved by the European Commission and Health Canada for the treatment of HIV in adults aged 12 and older.