formerly known as Myrcludex B, led to suppression of hepatitis delta virus
(HDV) and a functional cure of hepatitis B virus (HBV) in some people with both
viruses when combined with pegylated interferon-alfa-2a, according to a presentation at the 2019
International Liver Congress last week in Vienna.
results of this trial suggest that bulevirtide is a promising treatment for
chronic HDV infection, and that the combination of bulevirtide and peg-IFN-alfa
has the potential to cure HBV/HDV co-infection in some patients," said
Prof Heiner Wedemeyer of Essen University Hospital in Germany.
delta is a defective virus that can only replicate in the presence of HBV. Over
years or decades, chronic hepatitis B can lead to advanced liver disease
including cirrhosis, liver cancer and end-stage liver failure. Liver disease
progression is more aggressive in people with HBV/HDV co-infection than in those
with HBV alone.
There is currently no approved therapy for HDV, though
it is sometimes treated with peg-IFN-alfa. Nucleoside/nucleotide antivirals for
hepatitis B, such as tenofovir disoproxil fumarate (Viread), tenofovir alafenamide (Vemlidy)
and entecavir (Baraclude), can suppress HBV replication during therapy but usually
do not lead to a cure, as indicated by hepatitis B surface antigen
(HBsAg) clearance and antibody seroconversion.
is an experimental entry inhibitor that binds
to the receptor HBV uses to enter liver cells (known as sodium taurocholate co-transporting polypeptide or NTCP),
thereby both interfering with the lifecycle of HBV and preventing HDV
Wedemeyer presented findings from a phase 2b clinical trial assessing the safety and efficacy of bulevirtide plus pegylated interferon-alfa-2a.
last year's EASL meeting he presented a study of bulevirtide in
combination with tenofovir DF. That study showed that although
bulevirtide suppressed HBV and HDV replication, is usually did not lead to a
The present study included 60 people with
HBV/HDV co-infection. They were randomly allocated to four treatment arms:
- 180 mcg peg-IFN-alfa-2a alone
2mg bulevirtide plus peg-IFN-alfa-2a
- 5mg bulevirtide plus peg-IFN-alfa-2a
- 2mg bulevirtide alone.
Peg-IFN-alfa-2a was given as a once-weekly
subcutaneous injection while bulevirtide was given as a daily injection. All
participants were treated for 48 weeks with a 24-week follow-up period
after completing therapy.
HDV viral load levels fell steeply during
treatment in the two combination therapy arms and modestly in the bulevirtide
and peg-IFN-alfa monotherapy arms. But while HDV RNA levels rebounded after
stopping treatment in the two monotherapy and 5mg combination arm, it remained
suppressed in the 2mg combo arm, Wedemeyer reported.
Nine of 15 people (60%) taking the 2mg
bulevirtide combination and six of 15 (40%) taking the 5mg combo achieved
undetectable HDV RNA by the end of treatment at week 48, compared with two
people (13%) in each monotherapy arm. At 72 weeks, eight (53%) and four (27%)
people in the respective combination arms still had suppressed HDV, but no one in
the monotherapy arms had sustained suppression.
In addition, six of 15 people in the 2mg
combination arm and two of 15 in the 5mg combo arm had greater than a 1-log
decline or undetectable HBsAg at week 72. Looking at both combination arms
together, 27% had HBsAg loss and 20% experienced seroconversion, considered a
functional cure, according to Wedemeyer. No one taking either monotherapy had
HBsAg loss or seroconversion.
ALT liver enzyme normalisation was
observed in 37% of people taking the combinations and 67% of those on
bulevirtide alone at 48 weeks. But whereas ALT normalisation was sustained in
the combo arms, it was lost in the bulevirtide monotherapy arm.
Treatment was generally safe and well
tolerated. No serious adverse events occurred during the treatment period and
there were no discontinuations due to bulevirtide-related side-effects,
Wedemeyer reported. A total of 155 bulevirtide-related adverse events were
observed through week 72, most of them mild. Bile salts increased during
treatment but returned to normal soon after stopping therapy. Most adverse
events were related to peg-IFN-alfa, which is known to be difficult to
"Entry inhibition with [bulevirtide]
in combination with [peg-IFN-alfa-2a] bears curative potential in patients with
chronic hepatitis B/D co-infection," the researchers concluded.
"Presented data indicate a future role for the treatment of chronic
Wedemeyer noted that this is the largest
clinical trial and the best results ever seen for HDV. Given that virus levels
rebounded after stopping therapy, he said that longer treatment durations will
be explored in phase III studies.