Study data supports the long-term efficacy and safety of besifovir dipivoxil maleate (BSV) for the treatment of chronic hepatitis B (CHB), according to results published in the American Journal of Gastroenterology. BSV was effective both in patients who were treatment-naïve and patients with prior exposure to tenofovir disoproxil fumarate (TDF).
The 144-week study comprised a 48-week double-blind comparison period and a 96-week open-label period. The 48-week randomized clinical trial compared BSV and TDF for the treatment of CHB in patients living in South Korea. Eligible patients had a CHB duration <20 years and were positive for hepatitis B surface antigen (HBsAg). Researchers randomized patients 1:1 into BSV or TDF treatment groups for a 48 week span. To maintain the double-blind condition, patients in the BSV condition received L-carnitine 660 mg as a TDF placebo, while patients in the TDF condition received L-carnitine 660 mg as a BSV placebo. After 48 weeks, patients continued on BSV or were switched to BSV 150 mg with L-carnitine 660 mg for the open-label phase. The primary efficacy endpoint was the proportion of patients achieving virologic response, defined as HBV DNA <69 IU/mL at week 144. Other efficacy endpoints included the proportion of patients with undetectable HBV DNA levels (<20 IU/mL), alanine aminotransferase (ALT) normalization, and HBsAg and Hepatitis B e-antigen (HBeAg) seroconversion. Laboratory and clinical values were collected at 12-week intervals. Adverse events were monitored for the entire 144-week study period.
Of 197 patients initially randomized to TDF or BSV, 170 (86%) and 158 (80%) entered the second and third years of the open-label extension study, respectively. Overall, 153 patients completed all 144 weeks of follow-up. Of these, 81 patients were in the BSV-BSV group and 76 were in the TDF-BSV group. Across both groups, the majority of study completers were men (65.6%) and mean age was 45 years. At week 144, the rate of virologic response was 87.7% in the BSV-BSV group and 92.1% in the TDF-BSV group (P =.36). The proportion of patients achieving undetectable HBV DNA was 80.3% in the BSV-BSV group and 85.5% in the TDF-BSV group (P =.38). Neither group showed antiviral resistance during the study period. The BSV-BSV and TDF-BSV arms displayed comparable rates of ALT normalization (81.5% vs 88.2%; P =.25) and HBeAg seroconversion (8.0% vs 12.2%; P =.73). Significant improvements were observed in noninvasive fibrosis and cirrhosis in both groups. A total of 3 adverse events occurred during the 144 weeks: hepatocellular carcinoma (n=1) and hepatocellular carcinoma with type 2 diabetes (n=2). However, all 3 patients were permitted to continue the study. No deaths or incidents of acute kidney injuries were observed. The rates of adverse events were not significantly different between groups.
These data suggest that BSV treatment is effective and safe for the long-term treatment of CHB in both treatment-naïve and TDF-experienced patients. BSV response was maintained for 144 weeks, with no viral resistance observed. As study limitations, investigators noted that some markers of renal function—including urinary albumin and beta-2 microglobulin—were not evaluated. To achieve a fuller picture of BSV safety, further study which incorporates these markers of nephrotoxicity is necessary.
Disclosure: One study author declared affiliations with the pharmaceutical industry.
Please see the original reference for a full list of authors’ disclosures.
Yim HJ, Kim W, Ahn SH, et al. Besifovir Dipivoxil Maleate 144-week treatment of chronic hepatitis B: an open-label extensional study of a phase 3 trial [published online May 1, 2020]. Am J Gastroenterol. doi: 10.14309/ajg.0000000000000605