Tenofovir alafenamide for hepatitis B shows improved kidney and bone safety after a year

Liz Highleyman
Published:
08 January 2019

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 tissues.

Glossary

pro-drug

A 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.

The 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, Seto reported.

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."

Reference

Seto W-K et al. Bone and renal safety are improved in chronic HBV patients 1 year after switching to tenofovir alafenamide (TAF) from tenofovir disoproxil fumarate (TDF). AASLD Liver Meeting, abstract 0404, 2018.

View the abstract.