Gilead seeks Japanese approval for tenofovir alafenamide to treat chronic hepatitis B
Gilead Sciences, Inc, a biopharmaceutical company, announced that it has submitted a New Drug Application (NDA) to Japan’s Pharmaceutical and Medical Devices Agency (PMDA) for tenofovir alafenamide (TAF) 25 mg, an investigational once-daily treatment for adults with chronic hepatitis B virus (HBV) infection.
TAF is a novel targeted prodrug of tenofovir that has demonstrated high antiviral efficacy similar to and at a dose less than one-tenth that of Gilead’s Viread (tenofovir disoproxil fumarate, TDF), which is marketed in Japan for the treatment of HBV as Tenozet by GlaxoSmithKline. TAF has also demonstrated improvements in surrogate laboratory markers of renal and bone safety compared to TDF in clinical trials.
“With more than one million people in Japan chronically infected with hepatitis B, there is a significant need for effective new treatment options that offer a favorable safety profile,” said Norbert Bischofberger, PhD, Gilead’s executive vice president of research and development and chief scientific officer. “We are pleased with the results of the phase 3 studies, which suggest that TAF has the potential to improve the care of chronic hepatitis B patients who require lifelong treatment to manage their disease.”
The NDA for TAF is supported by 48-week data from two phase 3 studies, which met their primary objective of non-inferiority in efficacy (HBV DNA < 29 IU/ml at Week 48) compared to TDF among treatment-naïve and treatment-experienced adults with HBeAg-negative and HBeAg-positive chronic HBV infection. Both studies enrolled patients from a number of clinical sites in Japan. Patients randomized to the TAF arms showed a statistically significant increase in serum alanine aminotransferase normalization relative to the TDF arms when using the American Association for the Study of Liver Disease criteria. Changes in renal and bone laboratory safety parameters favored the TAF treatment arms. Overall, patients receiving TAF experienced a significantly smaller percentage decrease from baseline in hip and spine bone mineral density at week 48 compared to patients receiving Viread. Additionally, the overall change in serum creatinine from baseline to week 48 favoured TAF. Rates of discontinuations due to adverse events and the most commonly reported adverse events were similar in patients receiving TAF or Viread.
TAF as a single agent treatment for HBV is an investigational product and its safety and efficacy have not been established.