Vir Biotechnology, Inc. (NASDAQ: VIR) today announced additional
interim data from the ongoing Phase 2 trial in patients and results
from the Phase 1 trial in healthy volunteers of VIR-2218, an
investigational small interfering ribonucleic acid (siRNA) that
mediates RNA interference (RNAi) for the treatment of chronic
hepatitis B virus (HBV) infection.
Interim results from the ongoing Phase 2 trial demonstrate that
VIR-2218 results in a significant dose-dependent and durable
reduction in hepatitis B surface antigen (HBsAg) through Week 24 in
patients with chronic HBV who received two doses of VIR-2218,
ranging from 20 mg to 200 mg. Similar HBsAg reductions were
observed in both HBeAg- and HBeAg+ patients. In addition, VIR-2218
was generally well tolerated, with the majority of treatment
emergent adverse events (AEs) reported as mild in severity, and no
clinically significant alanine transaminase (ALT) elevations
observed.
“The rapid and sustained dose-dependent knockdown of
surface antigen observed in this trial with only 2 doses of
VIR-2218 is impressive,” said Edward J. Gane, M.D.,
Professor of Medicine at the University of Auckland, New Zealand
and Chief Hepatologist, Transplant Physician and Deputy Director of
the New Zealand Liver Transplant Unit at Auckland City Hospital.
“Notably, this response was seen in both the HBeAg- and HBeAg+
patient groups, demonstrating that this single siRNA can knock down
HBsAg in patients regardless of the stage of their
disease. Novel agents like VIR-2218 that reduce the high viral
antigen burden associated with chronic HBV infection will likely
become the cornerstone of future functional cure regimens.”
By targeting a conserved region of the HBV genome, VIR-2218 is
designed to inhibit the production of all HBV proteins, including
HBsAg. Suppression of HBV proteins, particularly HBsAg, is
hypothesized to remove the inhibition of T and B cell activity
directed against HBV. VIR-2218 was the first siRNA in the clinic to
include Alnylam Pharmaceutical, Inc.’s (NASDAQ:ALNY) Enhanced
Stabilization Chemistry-Plus (ESC+) technology to enhance stability
and minimize off-target activity, which may result in an enhanced
therapeutic index.
Dose-dependent HBsAg reductions in HBV
patients
In the ongoing Phase 2 trial, virally suppressed patients on
nucleos(t)ide reverse transcriptase inhibitor therapy (n=24)
received two subcutaneous 20, 50, 100, or 200 mg doses of VIR-2218
on Day 1 and Day 29. At Week 24, the mean change in HBsAg observed
with 20, 50, 100, and 200 mg was -0.76 log10, -0.93 log10, -1.23
log10, and -1.43 log10, respectively. Of note, all patients who
received the 200 mg dose level achieved a ≥1 log10 reduction in
HBsAg, with HBeAg- and HBeAg+ patients achieving similar mean
declines. There has been no dose-related trend in the frequency of
AEs observed during the trial, with the most common AE being
headache (n=6; 25%). No patients discontinued the trial due to an
AE.
ESC+ design suggests a potentially improved hepatic
safety profile
The Alnylam ESC+ technology incorporated into VIR-2218 is
designed to reduce off-target binding while maintaining on-target
activity, which is hypothesized to result in an improved hepatic
safety profile. In analyses of the in vitro, in vivo and Phase 1
clinical data, the ESC+ siRNA VIR-2218, when compared to the parent
compound ALN-HBV, which is not an ESC+ siRNA, was shown to
have:
- Improved in vitro specificity by reducing off-target effects on
host messenger RNA;
- Decreased propensity to cause ALT elevations in a humanized
liver chimeric mouse model; and
- In a cross-study comparison of Phase 1 data, decreased
propensity to cause ALT elevations in healthy volunteers at dose
levels anticipated to be clinically relevant.
Information on the potential hepatic safety profile of all
siRNAs is an important consideration in the HBV patient population,
especially those with advanced liver disease.
“We are pleased that the data from our VIR-2218 Phase 1/2
clinical trial continue to support the potential of this molecule
to be the backbone of a treatment regimen aimed at the functional
cure of chronic HBV infection,” said Phil Pang, M.D., Ph.D., Chief
Medical Officer of Vir. “Our next step will be to demonstrate
whether knockdown of HbsAg can result in high rates of functional
cure when VIR-2218 is given in combination with other agents, which
is the goal of our next set of trials. We expect the first of those
combination trials – combining VIR-2218 with a shortened course of
pegylated interferon - to begin dosing patients in the second half
of this year.”
Conference Call Information
Vir will discuss these results via a conference call today at
2:00 p.m. PT (5:00 p.m. ET). The call will include presentation by
Dr. Gane, who is the lead investigator for the VIR-2218 trials.
Participant Toll-Free Dial-In Number:
+1 (833)
727-9519Participant International Dial-In Number:
+1 (830) 213-7696
A live webcast of the presentation can be accessed under Events
& Presentations in the Investors section of the Vir website at
www.vir.bio and will be archived there following the presentation
for 30 days.
About Hepatitis B
Approximately 290 million people globally are chronically
infected with HBV and approximately 900,000 of them die from
HBV-associated complications each year. There is a significant
unmet medical need for more effective therapies that lead to
life-long control of the virus after a finite duration of therapy,
which is the definition of a functional cure. For a registrational
trial to demonstrate a functional cure, the formal endpoint
accepted by the U.S. Food and Drug Administration, or the FDA, is
undetectable HBsAg, defined as less than 0.05 international units
per milliliter, or IU/ml, as well as HBV DNA less than the lower
limit of quantification, in the blood six months after the end of
therapy. Currently, a year-long course of PEG-IFN-α is the best
available curative therapy. It has a low functional cure rate of
approximately three to seven percent. Alternatively, suppressive
therapy with nucleotide/nucleoside reverse transcriptase
inhibitors, or NRTIs, is commonly used, but patients often require
a lifetime of therapy.
About VIR-2218
VIR-2218 is a subcutaneously administered HBV-targeting siRNA
that has the potential to stimulate an effective immune response
and have direct antiviral activity against HBV. It is the first
siRNA in the clinic to include Enhanced Stabilization Chemistry
Plus (ESC+) technology to enhance stability and minimize off-target
activity, which potentially can result in an increased therapeutic
index. VIR-2218 is the first asset in the company’s collaboration
with Alnylam Pharmaceuticals, Inc. to enter clinical trials.
About Vir
Vir Biotechnology is a clinical-stage immunology company focused
on combining immunologic insights with cutting-edge technologies to
treat and prevent serious infectious diseases. Vir has assembled
four technology platforms that are designed to stimulate and
enhance the immune system by exploiting critical observations of
natural immune processes. Its current development pipeline consists
of product candidates targeting hepatitis B virus, influenza A,
SARS-CoV-2, human immunodeficiency virus, and tuberculosis. For
more information, please visit www.vir.bio.
Vir Forward-Looking Statements
This press release contains forward-looking statements within
the meaning of the Private Securities Litigation Reform Act of
1995. Words such as “may,” “will,” “expect,” “plan,” “anticipate,”
“estimate,” “intend,” “potential” and similar expressions (as well
as other words or expressions referencing future events, conditions
or circumstances) are intended to identify forward-looking
statements. These forward-looking statements are based on Vir’s
expectations and assumptions as of the date of this press release.
Each of these forward-looking statements involves risks and
uncertainties. Actual results may differ materially from these
forward-looking statements. Forward-looking statements contained in
this press release include statements regarding the potential
benefits of VIR-2218, the timing of VIR-2218 clinical trials, the
potential of ESC+ technology to enhance the safety of siRNAs and
statements regarding the potential benefits of Vir’s collaboration
with Alnylam Pharmaceuticals, Inc. Many factors may cause
differences between current expectations and actual results
including unexpected safety or efficacy data observed during
clinical trials, difficulties in obtaining regulatory approval,
challenges in accessing manufacturing capacity, clinical site
activation rates or clinical trial enrollment rates, changes in
expected or existing competition, delays or disruptions due to the
COVID-19 pandemic, and unexpected litigation or other disputes.
Other factors that may cause actual results to differ from those
expressed or implied in the forward-looking statements in this
press release are discussed in Vir’s filings with the U.S.
Securities and Exchange Commission, including the section titled
“Risk Factors” contained therein. Except as required by law, Vir
assumes no obligation to update any forward-looking statements
contained herein to reflect any change in expectations, even as new
information becomes available.
Contact:
InvestorsNeera Ravindran, MDHead of Investor
Relations & Strategic
Communicationsnravindran@vir.bio+1-415-506-5256
MediaLindy DevereuxScient
PRlindy@scientpr.com+1-646-515-5730
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