FDA approves tenofovir alafenamide for patients with chronic hepatitis B and liver disease
The Food and Drug Administration has approved tenofovir alafenamide (marketed as Vemlidy by Gilead Sciences) for the treatment of adults with chronic hepatitis B virus infection with compensated liver disease.
Tenofovir alafenamide is a novel, targeted prodrug of tenofovir that has demonstrated antiviral efficacy similar to tenofovir disoproxil fumarate (Viread) at significantly lower doses.
Approval for this drug was based on two international phase III clinical trials that, together, enrolled 1,298 treatment-naive and treatment-experienced adult patients with chronic hepatitis B virus infection, 425 of whom were HBeAg negative and 873 of whom were HBeAg positive. In both studies, participants were randomly treated with either tenofovir alafenamide or tenofovir disoproxil fumarate, and tenofovir alafenamide met the primary endpoint of noninferiority to tenofovir disoproxil fumarate, according to a written statement published by Gilead Sciences.
Compared with tenofovir disoproxil fumarate, tenofovir alafenamide has “greater plasma stability and more efficiently delivers tenofovir to hepatocytes” which allows tenofovir alafenamide to be administered in daily doses of 25mg while tenofovir disoproxil fumarate requires a dose of 300 mg to be as effective.
与富马酸替诺福韦二吡呋酯相比，替诺福韦艾拉酚胺具有“更好的血浆稳定性，能更有效地将替诺福韦转运至肝细胞，”从而使得替诺福韦艾拉酚胺有效每日剂量为25 mg，而富马酸替诺福韦二吡呋酯则需要300 mg剂量。
In addition, patients treated with tenofovir alafenamide demonstrated “improvements in certain bone and renal laboratory parameters.”
Overall, tenofovir alafenamide was well tolerated. Only 1% of patients discontinued treatment because of adverse events, and the most common adverse events were headache, abdominal pain, fatigue, cough, nausea, and back pain. Vemlidy has a boxed warning in its product label regarding the risks of lactic acidosis/severe hepatomegaly with steatosis and severe acute exacerbation of hepatitis B with discontinuation.
“Vemlidy is the first medication approved to treat this disease in nearly a decade,” said President and Chief Executive Officer of Gilead Sciences John Milligan. “We are excited to offer a new, effective option to help advance long-term care for patients.”