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FDA Approves HIV-1 Treatment That’s Easier on Kidneys and Bones

Genvoya is the first drug with tenofovir alafenamide to be approved by the agency

A combination tablet of elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide (Genvoya, Gilead Sciences) has been approved by the FDA as a drug cocktail to treat human immunodeficiency virus (HIV) patients.

According to Reuters, the combination was approved as a complete regimen for previously untreated patients weighing at least 35 kg (77 pounds). The drug also aims to treat adults whose HIV-1 infection is currently suppressed due to antiretroviral therapy. HIV-1 is the most common and pathogenic strain of the virus.

The combination is not recommended for patients with severe kidney problems, the FDA said. The treatment carries a boxed warning about potentially fatal risks such as buildup of lactic acid in the blood and severe liver problems. The label also states that the tablet is not approved to treat patients with chronic hepatitis B virus infection.

The combination of elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide was developed from Stribild, an older version of the four-drug cocktail. Stribild took in about $803 million in the first half of the year, according to a regulatory filing.

The new medication is indicated as a complete regimen for the treatment of HIV-1 infection in adults and pediatric patients 12 years of age and older who have no antiretroviral treatment history or to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA levels less than 50 copies per mL) on a stable antiretroviral regimen for at least six months with no history of treatment failure and no known substitutions associated with resistance to the four individual components. No dosage adjustment is required in patients with estimated creatinine clearance greater than or equal to 30 mL per minute.

Tenofovir alafenamide (TAF) is a novel targeted prodrug of tenofovir that has demonstrated high antiviral efficacy similar to and at a dose less than one-tenth that of Gilead’s Viread (tenofovir disoproxil fumarate, TDF), as well as improvement in surrogate laboratory markers of renal and bone safety as compared to TDF in clinical trials in combination with other antiretroviral agents. Data show that because TAF enters cells, including HIV-infected cells, more efficiently than TDF, it can be given at a lower dose and there is 91% less tenofovir in the bloodstream.

The new combination regimen was studied in a phase III HIV clinical program in more than 3,500 patients, including treatment-naïve, virologically suppressed, renally impaired, and adolescent patients. The approval is supported by 48-week data from two phase III double-blind studies among 1,733 treatment-naïve patients in which the regimen met its primary objective of noninferiority compared to Stribild (elvitegravir 150 mg, cobicistat 150 mg, emtricitabine 200 mg, and tenofovir disoproxil fumarate 300 mg [E/C/F/TDF]). In the combined analysis of the studies, 92.4% of patients using the new medication and 90.4% of Stribild patients had HIV-1 RNA levels less than 50 copies/mL at week 48. Tests of certain renal and bone laboratory parameters also favored the new combination over Stribild.

Additionally, the approval is supported by a phase 3 study evaluating the new combination among virologically suppressed patients who switched from TDF-based regimens. The study enrolled 1,436 subjects and 1,196 had reached the 48-week point at the time of filing. Among those patients, the new regimen was found to be noninferior to the TDF-based regimens based on the percentages of patients with HIV-1 RNA levels less than 50 copies/mL at week 48. Patients receiving the new regimen also demonstrated improvements in certain bone and renal laboratory parameters compared to those treated with the TDF-based regimens. Finally, data from phase III studies evaluating the new regimen among adolescents and patients with mild-to-moderate renal impairment supported the approval.

Sources:  Reuters, November 6, 2015; and Gilead, November 5, 2015.

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