These promising clinical trial
findings were borne out in the first real-world studies of bulevirtide since
Prof. Victor De Ledinghen of Bordeaux University
Hospital in France and colleagues looked at outcomes from the French early access
programme. The analysis included 145 patients with chronic HBV/HDV co-infection
who either had advanced fibrosis or compensated cirrhosis or moderate fibrosis and
elevated ALT levels.
two-thirds were men, and the average age was 41 years. About 15% also had HIV
co-infection. They were treated with 2mg bulevirtide once daily, either alone
(77 patients) or with pegylated interferon (68 patients), for at least one year.
Nearly 80% were also using nucleoside analogues to treat hepatitis B, and about
two-thirds had undetectable HBV DNA.
treated with bulevirtide alone, mean serum HDV RNA viral load declined by -3.64
at 12 months. Among those treated with bulevirtide plus pegylated interferon,
the corresponding reduction was -5.56 log IU/ml. People treated with bulevirtide
monotherapy were much less likely to reach an undetectable HDV viral load at 12
months than those who added pegylated interferon (39% vs 85%, respectively). However,
those on monotherapy were more likely to achieve a normal ALT level (49% vs
36%, respectively). Looking at a combined endpoint of undetectable HDV viral
load or at least a 2-log decline in HDV RNA plus ALT normalisation, 39% on
bulevirtide alone and 30% on bulevirtide and pegylated interferon met both
As in the
MYR301 trial, bulevirtide was generally well tolerated. In the monotherapy
group, 19 people modified and seven discontinued treatment for various reasons.
In the bulevirtide plus pegylated interferon group, five modified and 12
stopped treatment. Two and three patients, respectively, discontinued due to adverse
events. All but one person experienced the expected bile acid elevations.
real-life study, [bulevirtide] 2mg shows favourable HDV RNA and ALT
normalisation,” the researchers concluded. “HDV RNA levels continued to decline
throughout 12-month treatment.”
another analysis, Teresa Binter of the Medical University of
Vienna and colleagues assessed 17 patients who received bulevirtide, first
through a compassionate use programme and then through the Austrian health insurance
system. Eleven were women, the average age was 50 years and 65% had compensated
cirrhosis. Fifteen received 2mg bulevirtide once daily, but two used a 10mg
dose. Most were concurrently taking nucleoside analogues for hepatitis B and
had been unsuccessfully treated with pegylated interferon.
of patients saw at least a 2-log reduction in HDV RNA and about 90% experienced
ALT normalisation at 48 weeks. Four people achieved viral load suppression for
at least six months while on treatment. One person without cirrhosis who
started on a 10mg dose maintained an undetectable viral load for 20 weeks after
stopping treatment. Another received a 2mg dose of bulevirtide for 63 weeks and
maintained an undetectable viral load for six months, experienced viral rebound
four weeks after stopping treatment and restarted bulevirtide. A third
responder elected to stay on bulevirtide despite having viral suppression for more
than six months. Four non-responders added pegylated interferon, which led to
steep drops in HDV RNA, and they are still on treatment.
eradicate HDV, long-term treatment is needed. A response-guided approach is
recommended,” the investigators concluded, noting that an individualized approach is needed.
suggest starting with 2mg bulevirtide and measuring viral load at 24 weeks.
Those with at least a 2-log drop in HDV RNA should continue as long as viral
load continues to decline. Once HDV RNA is undetectable for at least six
months, they can stop treatment. Those with a less than a 2-log decline should
continue treatment for another 12 to 24 weeks and measure viral load again.
Those who still do not see a 2-log decline can add pegylated interferon. If
they still do not respond, the researchers advise stopping treatment due to