Gilead Sciences, Inc, a biopharmaceutical company, announced detailed 48-week results from two large phase 3 clinical trials (Studies 108 and 110) evaluating once-daily tenofovir alafenamide (TAF) 25 mg in treatment-naïve and treatment-experienced adults with HBeAg-negative and HBeAg-positive chronic hepatitis B virus (HBV) infection. Data were presented this week during two oral sessions (GS06 and GS12) at The International Liver Congress 2016 in Barcelona, Spain.
Both studies met their primary endpoints of non-inferiority to Gilead’s Viread (tenofovir disoproxil fumarate, TDF) 300 mg based on the percentage of patients with HBV DNA levels below 29 IU/ml at 48 weeks of therapy. In addition, TAF demonstrated improved renal and bone laboratory safety parameters compared to Viread. Discontinuations due to adverse events were uncommon in both treatment arms. The most commonly reported adverse events in both studies included headache, upper respiratory tract infection, nasopharyngitis and cough, and occurred at similar rates in patients receiving either TAF or Viread. A summary of the topline study results was disclosed in a press release dated January 5, 2016.
“Chronic hepatitis B infection is a life-threatening disease that can lead to liver failure, liver cancer and death,” said Norbert Bischofberger, PhD, executive vice president, research and development and chief scientific officer, Gilead Sciences. “With millions of people living with the disease, it remains a significant health concern worldwide. The TAF phase 3 results presented this week demonstrate its potential to advance the treatment of HBV – offering a similar efficacy profile to Viread with improved bone and renal safety parameters.”
Studies 108 and 110, led by Maria Buti, MD, PhD, Liver Unit, Hospital General Universitario Vall d'Hebron, Barcelona, Spain, and Henry L.Y. Chan, MD, head, Division of Gastroenterology and Hepatology, The Chinese University of Hong Kong, respectively, are randomized, double-blind, 96-week clinical trials among 1,298 treatment-naïve and treatment-experienced patients with chronic HBV infection. In Study 108, 425 HBeAg-negative patients were randomized 2:1 to receive TAF (n=285) or Viread (n=140). In Study 110, 873 HBeAg-positive patients were randomized 2:1 to receive TAF (n=581) or Viread (n=292).
The primary efficacy endpoint of both studies is the proportion of subjects with plasma HBV DNA levels below 29 IU/ml. Key secondary endpoints include change from baseline in bone mineral density at the hip and spine at week 48, and change from baseline in serum creatinine at week 48. Other secondary endpoints include alanine aminotransferases (ALT, an enzyme that serves as a measure of liver damage) normalization and change from baseline in eGFR at week 48.
Based on the results of Studies 108 and 110, Gilead submitted a New Drug Application to the US Food and Drug Administration (FDA) for TAF and the FDA has set a target review date under the Prescription Drug User Fee Act (PDUFA) of November 11, 2016. Gilead also has submitted regulatory applications for TAF in the European Union and Japan.
TAF as a single-agent for chronic HBV is an investigational product and its safety and efficacy have not been established.