Heiner Wedemeyer of Essen University Hospital in Germany presented the latest
results from a phase IIb study of another combination therapy for people with
HBV/HDV co-infection, bulevirtide with either pegylated interferon
alfa or TDF.
formerly known as Myrcludex B, is an experimental entry inhibitor that binds to the receptor
HBV uses to enter liver cells, interfering with the lifecycle of HBV and
thereby also preventing HDV replication.
main MYR203 trial enrolled 60 people who were randomly assigned to receive 2mg
or 5mg bulevirtide by subcutaneous injection once daily plus 180mcg pegylated interferon alfa injected once
weekly, 2mg bulevirtide alone or pegylated interferon alone for 48 weeks.
As Wedemeyer reported at this year's EASL
International Liver Congress, 50% of participants in the two combination arms had
undetectable HDV RNA at week 48, compared with 13% in the two monotherapy
groups. At week 72 – six months after completing treatment – 40% still had an
undetectable level and 40% experienced ALT normalisation. In addition, 27%
achieved hepatitis B surface antigen (HBsAg) loss and 20% experienced HBs
antibody seroconversion, considered a functional cure. No one in the monotherapy
arms experienced a sustained response.
AASLD meeting, Wedemeyer presented interim findings from
an extension phase of the study that evaluated 10mg daily bulevirtide plus
weekly pegylated interferon alfa or 5mg
twice-daily bulevirtide plus daily TDF for 48 weeks.
These two groups included 15 patients each, all in Russia. About three-quarters were men and the mean age was approximately 37 years. The median HDV
RNA level at baseline was 6.26 log10 IU/ml and the median FibroScan score was nearly 11.
At the end of treatment, 87% of those taking 10mg daily bulevirtide plus
had undetectable HDV viral load. The 48-week response rate in the 5mg twice-daily bulevirtide
plus TDF group was 40%. ALT normalisation rates at week 48 were 27% and 40%,
However, only one person taking the 10mg daily bulevirtide plus pegylated interferon regimen and no one
taking the TDF combination achieved HBsAg loss, failing to replicate the
promising functional cure rate seen in the main study. Seventy-two week follow-up results
Treatment was generally safe and well tolerated. Most adverse events
were attributable to pegylated interferon. No bulevirtide-related serious
adverse events or treatment discontinuations were reported. Injection site
reactions were uncommon. Almost everyone saw an asymptomatic increase in bile
salts, a known side effect of bulevirtide. In the main study, levels returned
to normal soon after stopping therapy.
Wedemeyer and colleagues concluded that 10mg bulevirtide per day
"is a safe and promising strategy for maintenance therapy of chronic
hepatitis D," and adding pegylated interferon alfa shows "a strong
Two phase III trials of bulevirtide, alone and in combination with
pegylated interferon alfa, are currently underway (NCT03852719 and NCT03852433).