January 08, 2016
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TAF safe, effective against HBV

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Once-daily tenofovir alafenamide was noninferior to Viread and reached its primary endpoint as a single-agent for chronic hepatitis B virus infection in two phase 3 clinical trials, according to a press release.

Tenofovir alafenamide (Gilead Sciences; TAF), a new form of tenofovir recently approved by the FDA for use in HIV-infected, treatment-naive patients, also improved renal and bone laboratory safety parameters in patients with HBV compared with Viread (tenofovir disoproxil fumarate, Gilead Sciences; TDF), the release said.

Norbert Bischofberger, PhD

Norbert Bischofberger

“An estimated 350 million people are living with chronic hepatitis B worldwide, and [TDF] is an effective treatment option for those appropriate to receive therapy,” Norbert Bischofberger, PhD, executive vice president of research and development and chief scientific officer at Gilead Sciences, said in the release. “We are pleased that the TAF phase 3 study results reflect high efficacy and improved renal and bone safety parameters similar to those seen in clinical studies evaluating TAF-based regimens for HIV. Like HIV, HBV is a chronic condition that requires prolonged therapy, and we look forward to the opportunity to offer patients an improved option that has the potential to advance the long-term treatment of HBV.”

The safety and efficacy of TAF in patients with chronic HBV were assessed in two randomized, double blind, 96-week studies. Study 108 included 425 patients negative for hepatitis B e antigen (HBeAG), and Study 110 included 873 patients positive for HBeAG. In each study, researchers randomly assigned patients 2:1 to 25 mg TAF or TDF. The primary efficacy endpoint at 48 weeks was the proportion of patients with plasma HBV DNA levels below 29 IU/mL.

In Study 108, 94% (n = 268) of negative-HBeAG patients receiving TAF and 92.9% (n = 130) of patients receiving TDF achieved HBV DNA below 29 IU/mL (95% CI, –3.6% to 7.2%). In Study 110, 63.9% (n = 371) of HBeAG-positive patients receiving TAF and 66.8% (n = 195) of patients receiving TDF achieved HBV DNA below 29 IU/mL (95% CI, –9.8% to 2.6%).   

In both studies, patients who received TAF yielded a smaller mean percentage decrease in hip and spine bone mineral density vs. patients receiving TDF (P < .001). The median change in glomerular filtration rates also favored TAF over TDF (P < .01), according to the release.

Few patients in both treatment arms stopped therapy due to adverse events (0.7% each in Study 108; 1% each in Study 110). The most frequent adverse events were headache, upper respiratory tract infection, nasopharyngitis and cough.

As a secondary endpoint, researchers measured alanine aminotransferase (ALT) normalization using a central laboratory cut-off value and the American Association for the Study of Liver Diseases (AASLD) criteria. They found that TAF showed a significant increase in ALT normalization compared with TDF when measuring levels based on AASLD criteria, which defines normalization at a lower level vs. the central laboratory cut-off value.

Based on these results, Gilead Sciences plans to submit regulatory applications for TAF early this year for the treatment of chronic HBV in the United States and the European Union, the release said.

Disclosure: Bischofberger is the executive vice president of research and development and chief scientific officer at Gilead Sciences.