Phase III data support long-term efficacy of TAF against HBV

Two phase III studies presented at EASL 2023 reflected the long-term efficacy of tenofovir alafenamide (TAF) for individuals with HBeAg*-positive and HBeAg-negative chronic hepatitis B virus (HBV).

“Patients with chronic HBV who have received TAF only and those who switched from tenofovir disoproxil fumarate (TDF) to TAF over 8 years had high rates of persistent viral suppression,” said Dr Maria Buti from the Hospital Universitario Vall d’Hebron, Barcelona, Spain, during her presentation.

At year 8, >90 percent of patients achieved viral suppression. The rates were 97–98 percent among those who were HBeAg-negative, and between 91 and 96 percent in the HBeAg-positive group. [EASL 2023, abstract OS-067]

Alanine aminotransferase (ALT) normalization rates were high in the TAF-only group, which were achieved early and maintained through year 8, as seen in both the central laboratory (>85 percent in both HBeAg subgroups) and the AASLD** 2018 criteria (78 percent for both). Among those who switched from TDF, ALT normalization increased in the open-label phase, aligning with the rates achieved in the TAF-only arm.

In the HBeAg-positive group, the rates of HBeAg loss and seroconversion among those who received TAF only progressively increased over 8 years to 46 percent and 31 percent, respectively. Similar rates were observed among those who switched from TDF (44–46 percent [HBeAg loss] and 27–33 percent [seroconversion]).

The rates of HBsAg*** loss (≤5 percent) were generally low across cohorts, ranging between 0 and 5 percent, as were the rates of HBsAg seroconversion. “Small mean declines in qHBsAg were seen at year 8,” noted Buti. The mean changes in log₁₀ IU/mL were between –0.50 and –1.09.

A total of 78 patients had cirrhosis at baseline (n=47 and 31 in the TAF-only and TDF-TAF arms, respectively). By year 8, about two-thirds had regression of cirrhosis as per FibroTest score <0.75.

“[Moreover,] there was no resistance to TAF at all annual timepoints,” noted Buti. “No amino acid substitutions in HBV polymerase/reverse transcriptase with reduced susceptibility to TAF were found through 8 years of treatment.”

Preferred first-line treatment

In the two trials, a total of 1,298 participants were initially randomized 2:1 to receive either TAF 25 mg QD or TDF 300 mg QD for 96 or 144 weeks. Following which, all patients transitioned to open-label TAF until the final analysis at year 8. Seventy-five percent of participants completed the open-label phase of both studies. About 63 percent were male, and the majority were Asian (~80 percent). More than 10 percent had cirrhosis/Metavir F4 at baseline based on FibroTest score ≥0.75.

Several studies have demonstrated the noninferiority of TAF, a nucleotide reverse transcriptase inhibitor, to TDF in terms of antiviral efficacy in viraemic and virally suppressed HBeAg-positive and HBeAg-negative individuals. It also trumped TDF in terms of ALT normalization and renal and bone safety in these patients. [J Hepatol 2018;68:672-681; Lancet Gastroenterol Hepatol 2016;1:196-206; Lancet Gastroenterol Hepatol 2016;1:185-195]

“[Taken together, the findings show that] treatment with TAF was highly effective in patients with chronic HBV,” said Buti. Together with existing literature, the current data clearly support TAF as the preferred first-line treatment in this patient setting.