- GSK plans to advance bepirovirsen into Phase 3 development
program in 1H 2023
CARLSBAD, Calif., Nov. 8, 2022
/PRNewswire/ -- Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) today
announced that GSK presented positive end of study data from the
Phase 2b B-Clear study of
bepirovirsen (formerly IONIS-HBVRx), an investigational
antisense oligonucleotide treatment for patients with chronic
hepatitis B virus (CHB). The results showed that treatment
with bepirovirsen resulted in sustained clearance of hepatitis B
surface antigen (HBsAg) and hepatitis B virus (HBV) DNA for 24
weeks after end of bepirovirsen treatment in people with CHB. The
study results were presented at the American Association for the
Study of Liver Diseases' (AASLD) The Liver Meeting® in
Washington, DC.
"Ionis is pleased with the results of the Phase 2b B-Clear study and to see bepirovirsen
advance to Phase 3 clinical studies for the potential to offer a
first-in-class therapy for people with CHB, including the
possibility of functional cures. With these clinically meaningful
results, we believe bepirovirsen has the potential to provide
significant benefit to the millions of people with this chronic
disease," said Richard S. Geary,
Ph.D., executive vice president, drug development at Ionis.
The results from the B-Clear Phase 2b study provide initial evidence that
bepirovirsen, as monotherapy or in combination with
nucleoside/nucleotide analogue (NAs), can deliver sustained
reductions in HBsAg and HBV viral DNA in specific patient groups.
The full results from the study are now available in The
New England Journal of Medicine.
In treatment arm 1 of the study, 9% of patients on NA treatment
and 10% of patients not on NA treatment achieved the primary
outcome of HBsAg levels below the Lower Limit of Quantification
(LLOQ) and HBV DNA levels below the LLOQ, respectively. This is
defined as a sustained response and was observed for 24 weeks post
last dose. In the study, sustained response rates were higher in
subjects with low baseline HBsAg (< 1000 IU/mL) than in those
with high baseline HBsAg (>1000 IU/mL). Patients with low
baseline hepatitis B surface antigen levels responded best to
treatment with bepirovirsen with 16% and 25% of patients achieving
the primary outcome in treatment arm 1 of the on NA and not on NA
cohort, respectively.
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
are generally taken for life. Bepirovirsen is uniquely designed to
reduce HBV replication and suppress HBsAg and stimulate innate
immunity which could potentially lead to functional cure.
Functional cure is largely defined as sustained, undetectable
levels of HBV DNA and HBsAg in the blood with or without generating
protective antibodies after a finite course of treatment.
Functional cure occurs when the virus is not eliminated from the
body but is at low levels that are undetectable in blood and can be
controlled by the immune system without medication.
GSK is exploring sequential treatment trials of bepirovirsen
with other therapeutic modalities, with the aim of increasing
functional cure rate in more patients and reducing the overall
burden of CHB. These include:
- Phase 2b study of bepirovirsen in
sequential combination with pegylated interferon (PegIFN)
treatment
- Phase 2 study of bepirovirsen in sequential combination with
GSK's chronic hepatitis B targeted immunotherapy
About the B-Clear Phase 2b
study
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 the 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 one of four treatment
arms within each cohort, with treatment administered weekly with or
without loading doses (LD) on days four 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.
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 is an investigational antisense oligonucleotide
(ASO) designed to specifically recognize the RNA that the hepatitis
B virus uses to replicate itself in the infected liver cells
(hepatocytes) and make the viral antigens (proteins) which
facilitate chronicity of the disease by helping to avoid clearance
by the immune system. The ASO recruits the liver's own enzymes to
eliminate the RNA by digesting it to an active form. The subsequent
reduction in the levels of the RNA results in a decrease in both
the virus and the production of viral antigen (HBsAg) by the
hepatocytes, which can be measured by a drop in the HBV DNA and
antigen levels in the circulating blood.
Bepirovirsen (formerly IONIS-HBVRx), also known as
GSK3228836, was discovered, and jointly developed with GSK. GSK
licensed bepirovirsen from Ionis in August
2019 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 December 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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SOURCE Ionis Pharmaceuticals, Inc.