A pair of phase 3 studies have shown that Gilead Sciences’ new tenofovir alafenamide (TAF) suppresses hepatitis B virus (HBV) as well as the current tenofovir disoproxil fumarate (TDF) formulation, but with less detrimental effects on the kidneys and bones, the company has announced.
TAF is a pro-drug that delivers its active agent, tenofovir diphosphate, to infected cells more efficiently than the TDF formulation (Viread). TDF is considered generally safe and well-tolerated, but it can cause a small amount of bone loss soon after starting therapy and can lead to kidney problems in susceptible individuals.
TAF produces adequate intracellular drug levels with smaller doses than TDF, which means lower concentrations in the blood and less drug exposure for the kidneys, bones, and other organs and tissues.
TDF is an approved treatment for hepatitis B. It is highly effective in suppressing HBV long-term, though like other nucleoside/nucleotide analog antivirals it usually does not lead to a cure, as indicated by hepatitis B surface antigen loss and development of anti-HBs antibodies.
Study 108 and 110 showed that TAF and TDF were equally likely to reduce HBV DNA levels to below the limit of detection in treatment-naive and previously treated hepatitis B patients. But TAF led to somewhat greater improvement in ALT liver enzyme levels, as well as more favorable kidney lab tests and less hip and spine bone loss.
In November the US Food and Drug Administration approved Genvoya, the first combination pill containing TAF for the treatment of HIV. Gilead has also requested approval of another HIV single-tablet regimen containing TAF and a dual coformulation of TAF and emtricitabine (a successor to Truvada). TAF is being developed as a stand-alone drug for hepatitis B treatment.