Experimental Hepatitis B Drug Shows Strong Efficacy and Safety Profile

A study found the experimental drug tenofovir alafenamide (TAF) maintained efficacy and was safer than tenofovir disoproxil fumarate (Viread, TDF), in patients with chronic hepatitis B virus (HBV).

A pair of randomized, double-blind, phase 3 clinical trials were conducted over a 96-week period, with participants who were either hepatitis B e antigen (HBeAg)-positive or HBeAg-negative. Each patient was randomized to receive either TAF 25-mg daily or TDF 300-mg daily.

The primary efficacy endpoint was the percentage of patients with HBV DNA below 29 IU/mL at week 48. The key safety endpoints were changes in hip and spine bone mineral density, changes in serum creatinine, and dipstick proteinuria.

Both studies also assessed the markers of bone formation and resorption, as well as renal tubular function.

The results of the study showed that 94% of HBeAg-negative patients receiving TAF and nearly 93% receiving TDF achieved the primary endpoint.

In HBeAg-positive patients, nearly 64% who received TAF and almost 67% who received TDF achieved the primary endpoint.

The response rates in both studies met the primary endpoint of non-inferiority of TAF compared to TDF.

“These 2 studies demonstrate that treatment with tenofovir alafenamide is as effective and yet safer than treatment with tenofovir disoproxil fumarate,” said lead author of one of the studies, Maria Buti. “Patients with HBV require long-term treatment and we are pleased that these results could provide a potentially safer treatment regimen in the future.”

During both studies, the TAF group saw a significantly smaller mean percentage decrease from baseline in hip and spine bone mineral density at week 48 (p<0.001), as well as smaller changes in renal tubular markers (p<0.001) than TDF.

The HBeAg-positive study found that a smaller increase in serum creatinine was observed in patients receiving TAF (p=0.02).

The median change in estimated glomerular filtration rate (eGFR) from baseline to week 48 favored TAF in both studies (p<0.01). Additionally, both studies showed low rates of treatment discontinuation and serious adverse events.

“While tenofovir disoproxil fumarate is an effective treatment option for patients with chronic hepatitis B, we are pleased that this treatment, TAF, could provide patients with an equally effective and yet safer treatment option,” said EASL Vice Secretary Tom Hemming Karlsen.