FDA News

FDA approves Genvoya as first TAF-based HIV regimen

Genvoya, a fixed-dose combination tablet containing elvitegravir, cobicistat, emtricitabine and tenofovir alafenamide, was approved by the FDA today for the treatment of HIV-1 infection in patients aged 12 years or older, according to a press release.

“Today’s approval of a fixed-dose combination containing a new form of tenofovir provides another effective, once-daily complete regimen for patients with HIV-1 infection,” Edward Cox, MD, director of the FDA’s office of antimicrobial products, said in the release.

Edward Cox

Edward Cox

Genvoya (E/C/F/TAF, Gilead Sciences) is approved for use in HIV-infected, treatment-naive patients weighing at least 35 kg and HIV-infected adults with suppressed viral loads. The regimen is not recommended for patients with severe renal impairment. The formulation includes 150 mg elvitegravir, 150 mg cobicistat, 200 mg emtricitabine and 10 mg tenofovir alafenamide.

The approval is based on the results of four clinical trials that evaluated the safety and efficacy of the fixed-combination tablet in 3,171 patients with HIV across 21 countries. E/C/F/TAF met its primary endpoint of noninferiority in two phase 3, double blind studies comparing it with the drug manufacturer’s Stribild (elvitegravir, cobicistat, emtricitabine, tenofovir disoproxil fumarate [E/C/F/TDF]), according to Gilead. In the combined analysis of the studies, 92.4% of patients who received E/C/F/TAF and 90.4% of patients who received E/C/F/TDF had HIV-1 RNA levels less than 50 copies/mL after 48 weeks of treatment. Another phase 3 study assessing E/C/F/TAF in 1,436 virologically suppressed patients who switched from TDF-based regimens also found it was noninferior to prior treatments. The fourth phase 3 trial assessed E/C/F/TAF in adolescents and patients with mild-to-moderate renal impairment and found that the drug appeared to be associated with less kidney toxicity and bone density, and increased greater levels of serum lipids compared with other TDF regimens.

E/C/F/TAF contains a new form of tenofovir that has not been previously approved, according to the release. The formulation reduces adverse events by delivering lower levels of tenofovir in the bloodstream and higher levels within the HIV-replicating cells. The amount of tenofovir released in the bloodstream is reduced by 91% compared with Viread (TDF, Gilead Sciences), according to a company press release.

David Wohl, MD

David A. Wohl

“As the HIV patient population ages, there is an increased risk for development of age- and treatment-related comorbidities, including low bone mineral density and renal impairment,” David A. Wohl, MD, associate professor of medicine at the University of North Carolina at Chapel Hill and lead researcher of the E/C/F/TAF efficacy analysis, said in a press release. “This is due to the combination of HIV infection, antiretroviral treatments and the natural aging process. Given its demonstrated efficacy and safety profile, Genvoya represents an important new treatment option for a range of patients who are either new to therapy or who choose to switch treatments.”

The new treatment carries a boxed warning alerting health care providers that the drug can cause a buildup of lactic acid in the blood as well as severe liver problems, and that E/C/F/TAF is not approved to treat chronic hepatitis B virus infection. The FDA reported the most common adverse event associated with E/C/F/TAF is nausea. Other adverse events include new or worsening kidney problems, decreased bone mineral density, fat redistribution and immune reconstitution syndrome. The FDA recommends that patients are monitored for kidney and bone side effects.

The FDA is currently evaluating two other TAF-based regimens, according to Gilead, including an investigational, fixed-dose combination of emtricitabine and tenofovir alafenamide in combination with other ART, and a once-daily single tablet regimen that combines emtricitabine, tenofovir alafenamide and Edurant (rilpivirine, Janssen Therapeutics).

Disclosure: Wohl is the lead investigator for the Genvoya efficacy analysis.

Genvoya, a fixed-dose combination tablet containing elvitegravir, cobicistat, emtricitabine and tenofovir alafenamide, was approved by the FDA today for the treatment of HIV-1 infection in patients aged 12 years or older, according to a press release.

“Today’s approval of a fixed-dose combination containing a new form of tenofovir provides another effective, once-daily complete regimen for patients with HIV-1 infection,” Edward Cox, MD, director of the FDA’s office of antimicrobial products, said in the release.

Edward Cox

Edward Cox

Genvoya (E/C/F/TAF, Gilead Sciences) is approved for use in HIV-infected, treatment-naive patients weighing at least 35 kg and HIV-infected adults with suppressed viral loads. The regimen is not recommended for patients with severe renal impairment. The formulation includes 150 mg elvitegravir, 150 mg cobicistat, 200 mg emtricitabine and 10 mg tenofovir alafenamide.

The approval is based on the results of four clinical trials that evaluated the safety and efficacy of the fixed-combination tablet in 3,171 patients with HIV across 21 countries. E/C/F/TAF met its primary endpoint of noninferiority in two phase 3, double blind studies comparing it with the drug manufacturer’s Stribild (elvitegravir, cobicistat, emtricitabine, tenofovir disoproxil fumarate [E/C/F/TDF]), according to Gilead. In the combined analysis of the studies, 92.4% of patients who received E/C/F/TAF and 90.4% of patients who received E/C/F/TDF had HIV-1 RNA levels less than 50 copies/mL after 48 weeks of treatment. Another phase 3 study assessing E/C/F/TAF in 1,436 virologically suppressed patients who switched from TDF-based regimens also found it was noninferior to prior treatments. The fourth phase 3 trial assessed E/C/F/TAF in adolescents and patients with mild-to-moderate renal impairment and found that the drug appeared to be associated with less kidney toxicity and bone density, and increased greater levels of serum lipids compared with other TDF regimens.

E/C/F/TAF contains a new form of tenofovir that has not been previously approved, according to the release. The formulation reduces adverse events by delivering lower levels of tenofovir in the bloodstream and higher levels within the HIV-replicating cells. The amount of tenofovir released in the bloodstream is reduced by 91% compared with Viread (TDF, Gilead Sciences), according to a company press release.

David Wohl, MD

David A. Wohl

“As the HIV patient population ages, there is an increased risk for development of age- and treatment-related comorbidities, including low bone mineral density and renal impairment,” David A. Wohl, MD, associate professor of medicine at the University of North Carolina at Chapel Hill and lead researcher of the E/C/F/TAF efficacy analysis, said in a press release. “This is due to the combination of HIV infection, antiretroviral treatments and the natural aging process. Given its demonstrated efficacy and safety profile, Genvoya represents an important new treatment option for a range of patients who are either new to therapy or who choose to switch treatments.”

The new treatment carries a boxed warning alerting health care providers that the drug can cause a buildup of lactic acid in the blood as well as severe liver problems, and that E/C/F/TAF is not approved to treat chronic hepatitis B virus infection. The FDA reported the most common adverse event associated with E/C/F/TAF is nausea. Other adverse events include new or worsening kidney problems, decreased bone mineral density, fat redistribution and immune reconstitution syndrome. The FDA recommends that patients are monitored for kidney and bone side effects.

The FDA is currently evaluating two other TAF-based regimens, according to Gilead, including an investigational, fixed-dose combination of emtricitabine and tenofovir alafenamide in combination with other ART, and a once-daily single tablet regimen that combines emtricitabine, tenofovir alafenamide and Edurant (rilpivirine, Janssen Therapeutics).

Disclosure: Wohl is the lead investigator for the Genvoya efficacy analysis.