- Interim analysis of
B-Clear clinical study of bepirovirsen demonstrated
end-of-treatment virologic response (VR) in patients with chronic
hepatitis B
- Phase 3 clinical study
evaluating bepirovirsen as a monotherapy is anticipated to
start in the first half of 2023
- GSK to explore
potential combination treatments to further reduce the global
burden of chronic hepatitis B
CARLSBAD, Calif., June 25,
2022 /PRNewswire/ -- Ionis Pharmaceuticals, Inc.
(Nasdaq: IONS), today announced that GSK presented positive results
from an interim analysis of the Phase 2b B-Clear clinical study of bepirovirsen
(formerly IONIS-HBVRx), an investigational antisense
medicine for the treatment of patients with chronic hepatitis B
virus (CHB).
The data were presented in an oral late-breaker session at the
European Association for the Study of the Liver's (EASL)
International Liver Congress™ 2022 in London, UK. The final results from the study
will be submitted for presentation at a scientific congress later
this year, and for publication in a peer-reviewed journal.
"Chronic hepatitis B represents a significant healthcare
challenge for which there is particular need for new treatments
that provide a longer-lasting solution. Data from the Phase
2b B-Clear study demonstrated the
potential of bepirovirsen to provide rapid reductions in hepatitis
B surface antigen in both patients not on nucleoside analogue
treatment and those on stable NA therapy. These findings, together
with results of previous clinical studies, support GSK's plan to
initiate a Phase 3 clinical study evaluating bepirovirsen," said
Sanjay Bhanot, M.D., Ph.D., senior
vice president, chief medical officer and metabolic and liver
franchise leader at Ionis.
In the study, 28% of patients on standard of care, which is
stable nucleoside/nucleotide analogue (NA), and 29% of patients not
on NA treatment, experienced a virologic response (VR) on 300 mg of
bepirovirsen weekly, following 24 weeks of treatment. Virologic
response is defined as serum/plasma levels of hepatitis B virus
(HBV) DNA and hepatitis B surface antigens (HBsAg) below the lower
limit of quantification. Up to 68% of patients on NA therapy and up
to 65% of patients not on NA achieved HBsAg <100 IU/mL at the
end of treatment.
End-of-treatment virologic responses were observed in patients
with high or low baseline HBsAg levels, who were hepatitis B
e-antigen (HBeAg) negative or positive, and who were receiving NA
treatment or not, indicating that bepirovirsen has the potential to
treat broad segments of the CHB population. Durability of the
responses is being assessed.
Treatment-related serious adverse events (SAEs) were observed in
<1% of patients receiving NA treatment and 1% of patients who
were not on NA. SAEs were reported in 3% and 4% of patients
receiving NA treatment and those who were not on NA, respectively.
There were no clinically meaningful differences in adverse events
across treatment arms in either trial.
Chronic hepatitis B infection is caused by HBV and is a major
global health concern, affecting nearly 300 million people
worldwide.i,ii
Currently, nucleoside/nucleotide analogues are the
recommended first-line therapy for patients with chronic
HBV because they can inhibit viral
replication. However, they cannot clear the virus and must be
taken for life. Bepirovirsen is uniquely designed to reduce HBV
replication and suppress HBsAg which could potentially lead to
functional cure, largely defined as sustained, undetectable levels
of hepatitis B virus DNA and HBsAg in the blood with or without
generating protective antibodies after a finite course of
treatment.
GSK is also exploring combinations of bepirovirsen and other
therapeutic modalities in the following trials. Combination
treatments could increase functional cure rates in more patients,
thereby further reducing the global disease burden of CHB. Trials
include:
- Phase 2b trial of bepirovirsen in
sequential combination with pegylated interferon (PegIFN)
treatment
- Phase 2 trial of bepirovirsen in combination with GSK's chronic
hepatitis B targeted immunotherapy
About the B-Clear Phase
2b trial
The B-Clear Phase 2b study is
investigating the efficacy and safety of 12- or 24-weeks treatment
with bepirovirsen in people living with CHB on stable NA treatment
or not on NA treatment at study start. The primary endpoints are
the proportion of patients achieving HBsAg levels below the Lower
Limit of Quantification (LLOQ), and HBV DNA levels below LLOQ
sustained for 24 weeks without rescue medication after end of
treatment with bepirovirsen.
The study consists of two parallel cohorts, one for patients
receiving NA treatment and the other for patients who were not on
NA. Patients from each arm were randomized to 1 of 4 treatment arms
within each cohort, with treatment administered weekly with or
without loading doses (LD) on days 4 and 11:
- Bepirovirsen 300 mg with LD for 24 weeks;
- Bepirovirsen 300 mg with LD for 12 weeks then 150 mg for 12
weeks;
- Bepirovirsen 300 mg with LD for 12 weeks then placebo for 12
weeks;
- Placebo with LD for 12 weeks then bepirovirsen 300 mg without
LD for 12 weeks.
In both cohorts, virologic responses were observed at the end of
treatment:
- For those patients receiving NA treatment (n=227), 24 weeks
treatment of 300 mg bepirovirsen weekly resulted in HBsAg < LLOQ
and HBV DNA < LLOQ in 28% of patients at end of treatment.
- For patients not on NA (n=230), 24 weeks treatment of 300 mg
bepirovirsen weekly resulted in HBsAg < LLOQ and HBV DNA <
LLOQ in 29% of patients at end of treatment.
- The durability of these responses is being assessed.
About Hepatitis B virus
infection
Hepatitis B virus infection is a serious health problem that can
lead to significant and potentially fatal health conditions,
including cirrhosis, liver failure and liver cancer. Chronic
hepatitis B infection is caused by the hepatitis B virus and is a
major global health concern, affecting nearly 300 million people
worldwide.i,ii Chronic HBV
infection is one of the most common persistent viral infections in
the world. Currently available therapies, although effective in
reducing circulating HBV DNA in the blood, do not efficiently
inhibit HBV antigen production and secretion.
About Bepirovirsen
Bepirovirsen (formerly IONIS-HBVRx), also known as
GSK3228836, is an investigational antisense medicine Ionis designed
to reduce the production of viral proteins associated with
hepatitis B virus (HBV) infection and replication, including
hepatitis B surface antigen, which is present in both acute and
chronic infections and is associated with a poor prognosis in
patients with chronic HBV infection. GSK licensed bepirovirsen from
Ionis under a collaborative development and licensing
agreement.
About Ionis Pharmaceuticals,
Inc.
For more than 30 years, Ionis has been the leader in
RNA-targeted therapy, pioneering new markets and changing standards
of care with its novel antisense technology. Ionis currently has
three marketed medicines and a premier late-stage pipeline
highlighted by industry-leading cardiovascular and neurological
franchises. Our scientific innovation began and continues with the
knowledge that sick people depend on us, which fuels our vision of
becoming a leading, fully integrated biotechnology company.
To learn more about Ionis, visit www.ionispharma.com and
follow us on Twitter @ionispharma.
Ionis' Forward-looking
Statements
This press release includes forward-looking statements regarding
Ionis' business and the therapeutic and commercial potential of
Ionis' technologies, bepirovirsen and other products in
development. Any statement describing Ionis' goals, expectations,
financial or other projections, intentions or beliefs is a
forward-looking statement and should be considered an at-risk
statement. Such statements are subject to certain risks and
uncertainties, including those related to the impact COVID-19 could
have on our business, and including but not limited to, those
related to our commercial products and the medicines in our
pipeline, and particularly those inherent in the process of
discovering, developing and commercializing medicines that are safe
and effective for use as human therapeutics, and in the endeavor of
building a business around such medicines. Ionis' forward-looking
statements also involve assumptions that, if they never materialize
or prove correct, could cause its results to differ materially from
those expressed or implied by such forward-looking statements.
Although Ionis' forward-looking statements reflect the good
faith judgment of its management, these statements are based only
on facts and factors currently known by Ionis. As a result, you are
cautioned not to rely on these forward-looking statements. These
and other risks concerning Ionis' programs are described in
additional detail in Ionis' annual report on Form 10-K for the year
ended Dec. 31, 2021, and the most recent Form 10-Q quarterly
filing, which is on file with the Securities and Exchange
Commission. Copies of these and other documents are available from
the Company.
In this press release, unless the context requires otherwise,
"Ionis," "Company," "we," "our," and "us" refers to Ionis
Pharmaceuticals and its subsidiaries.
Ionis Pharmaceuticals® is a trademark of Ionis
Pharmaceuticals, Inc.
i Trepo C, et al. Hepatitis B virus infection.
Lancet. 2014 Dec 6; 384(9959):
2053-63. https://doi.org/10.1016/S0140-6736(14)60220-8
ii World Health Organization,
https://www.who.int/news-room/fact-sheets/detail/hepatitis-b
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