Tenofovir alafenamide (TAF; Vemlidy), the new formulation of
tenofovir, continues to appear at least equally effective for treatment of
hepatitis B but with a better safety profile than the older tenofovir
disoproxil fumarate (TDF; Viread),
according to a presentation at the recent AASLD Liver Meeting in San Francisco.
Nucleoside/nucleotide antivirals such as tenofovir and
entecavir (Baraclude) can suppress hepatitis B virus (HBV) replication
indefinitely but they seldom lead to a cure, necessitating long-term
therapy for many people.
TDF is generally considered
safe and well tolerated for treatment of both HBV and HIV, but it can cause bone
loss soon after starting treatment and can lead to kidney problems in
susceptible patients. TAF is a pro-drug formulation that produces a high level
of the active drug (tenofovir diphosphate)
in liver cells with a smaller dose than TDF, which means lower concentrations
in the blood and less drug exposure for the kidneys, bones and other organs and
drug that is broken down into another active form inside the body.
Wai-Kay Seto of Queen Mary Hospital in
Hong Kong presented findings from a pooled analysis of bone and kidney safety in
a pair of pivotal phase III trials comparing TAF and TDF for the treatment of
chronic hepatitis B.
Study 108 enrolled 425
hepatitis B 'e' antigen (HBeAg) negative participants and Study 110 enrolled
873 HBeAg positive participants in 17 countries. In both
studies combined, about two-thirds were men, nearly 80% were Asian and the average age
was approximately 40 years. Nearly a quarter had previously been treated for
hepatitis B and about 10% had liver cirrhosis.
Participants in both studies were randomly
assigned to receive 25mg TAF or 300mg TDF once daily.
Researchers presented the primary
48-week safety and efficacy results in 2016, showing that TAF
worked as well as TDF but with better kidney and bone safety. A follow-up
report showed continued effectiveness at 96 weeks. At that point,
half of the participants were assigned to remain on double-blind treatment
while the rest rolled over to open-label TAF
At The Liver Meeting, Wai-Kay Seto of Queen Mary Hospital in Hong Kong
presented findings from a pooled analysis of efficacy and safety from week 96 through week 144 in
211 people initially randomised to TDF who continued on that drug and 180
people who switched to TAF at week 96.
demographics of this subgroup were similar to the study population as a whole.
About 30% were over 50; older age is a risk factor for both kidney function
decline and bone loss, especially in postmenopausal women. At baseline, nearly
30% had below normal bone mineral density at the hip and nearly half had reduced
BMD at the spine.
At 144 weeks, 88% of ongoing TDF recipients and 84%
of those who switched to TAF had undetectable HBV DNA (< 29 IU/ml). Based on
AASLD criteria, 65% and 72%, respectively, had ALT liver enzyme normalisation.
Cures were rare, however: just 6% and 10% in the two groups achieved HBeAg loss
and no one achieved hepatitis B surface antigen (HBsAg) loss.
Treatment remained generally safe and well tolerated.
Only 4% in the ongoing TDF group and 6% in the TAF switch group had serious
adverse events and no one discontinued treatment due to side-effects.
Looking at kidney function, estimated glomerular filtration rate (eGFR)
improved in people who switched to TAF but remained stable in
those who stayed on TDF. Just 4% of people who switched to TAF saw their
chronic kidney disease worsen by one stage or more, but this rose to 12% for
those still on TDF. Markers of kidney tubule function improved in those who
switched, but no significant changes were observed in urine protein levels,
Turning to bone safety, bone mineral density at the
hip and spine rose significantly in the TAF switch group (by +0.98% and +2.04%
from baseline, respectively) while remaining the same in the ongoing TDF
group. More people in the TAF switch group saw either 0-3% or more than 3%
improvement – especially at the spine – while more people in the ongoing TDF group
saw declines. Serum biomarkers of bone turnover also improved more in
participants who switched to TAF.
Based on these
findings, the researchers concluded that people who switched from TDF to TAF
had "similar high rates of viral suppression" with "significant improvements
in bone and renal safety at 1 year."