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Tenofovir alafenamide works well against hepatitis B with less effect on bones and kidneys
Liz Highleyman, 2016-04-18 09:00:00
The new tenofovir alafenamide (TAF) pro-drug is as potent against hepatitis B virus (HBV) as the current tenofovir disoproxil fumarate (TDF) formulation, but with fewer detrimental effects on bone and kidney biomarkers, according to a pair of studies presented at the International Liver Congress last week in Barcelona.
Gilead Science’s tenofovir disoproxil fumarate (Viread) is one of the most effective antiviral drugs for hepatitis B and one of the most widely used antiretrovirals for HIV. It is generally considered safe and well tolerated, but it can cause a small amount of bone loss soon after starting therapy and can lead to kidney problems in susceptible people.
Nucleoside/nucleotide analogues like tenofovir can effectively suppress HBV replication during treatment, but they usually do not lead to a cure – as indicated by hepatitis B surface antigen (HBsAg) loss and development of anti-HBs antibodies – so long-term therapy is generally needed.
TAF is a new pro-drug formulation that produces high levels of the active drug (tenofovir diphosphate) in hepatocytes and CD4 T-cells with smaller doses than TDF, which means lower concentrations in the blood and less drug exposure for the kidneys, bones, and other organs and tissues.
In November 2015, the US Food and Drug Administration (FDA) approved Genvoya, the first combination pill containing TAF for the treatment of HIV; two other TAF co-formulations, Odefsey and Descovy, have since been approved. In addition, TAF is being developed as a stand-alone drug for hepatitis B treatment.
Maria Buti of Hospital General Universitari Vall d’Hebron in Barcelona and Henry Chan of the Chinese University in Hong Kong presented 48-week results from parallel phase 3 hepatitis B trials, the first enrolling people with hepatitis B 'e' antigen (HBeAg)-negative disease and the second enrolling harder-to-treat HBeAg-positive people.
The HBeAg-negative trial (Study 108) enrolled 425 participants; 61% were men, about 70% were Asian and the average age was 45 years. About 20% had previously been treated for hepatitis B. Most had HBV genotypes B, C or D (21, 40 and 32%, respectively in the TAF arm. The mean HBV DNA level was approximately 5.7 log10, with nearly 20% having 7 log10 or greater. Participants had alanine aminotransferase (ALT) levels within twice the upper limit of normal, with a median of 67 U/l. About 12% had a FibroTest score suggesting liver cirrhosis.
The HBeAg-positive trial (Study 110) included 873 participants; about 64% were men, 80% were Asian, the mean age was 38 years and a quarter had prior treatment experience. Genotypes B, C and D were again most common (17, 52 and 23% in the TAF arm). The mean HBV DNA level was higher in this study, at 7.6 log10, with about half having 8 log10 or greater. The median ALT level was 85 U/l and 8% had suspected cirrhosis.
Participants in both studies were randomly assigned to receive 25mg TAF or 300mg TDF once daily. Profs Buti and Chan reported the proportion of people with undetectable HBV DNA (<29 IU/ml) at week 48, the primary endpoint. The randomised studies will continue through 96 weeks, at which point everyone will receive open-label TAF.
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