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.
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
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.
A test that uses
results from blood tests to predict liver damage.
drug that is broken down into another active form inside the body.
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
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.
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.
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.