– Monthly tobevibart and elebsiran combination
achieves rapid 100% virologic suppression at Week 24, sustained
through Week 60 –
– Undetectable HDV RNA in 41% of participants
at Week 24, increasing to 64% by Week 36 and up to 80% by Week 60
across cohorts –
– Combination well-tolerated: no
treatment-related severe AEs, treatment-related discontinuations or
ALT flares –
– Following a recent FDA meeting, Phase 3
ECLIPSE registrational program to begin in the first half of 2025
–
– New data presented at AASLD The Liver
Meeting. Investor conference call November 19, 2024, at 5.15 a.m.
PT / 8.15 a.m. ET –
Vir Biotechnology, Inc. (NASDAQ:VIR) today announced positive
results from the SOLSTICE Phase 2 clinical trial evaluating
tobevibart alone, or in combination with elebsiran, in people with
chronic hepatitis delta (CHD). The most-advanced and potential
first-of-its-kind investigational human monoclonal antibody and
siRNA combination dosed monthly achieved 100% virologic response
and rapid hepatitis delta virus (HDV) RNA suppression. HDV RNA
below the lower limit of quantification (< LLOQ), target not
detected (TND), the best measure that the virus is cleared from the
body, was achieved in 41% (13/32) of participants at Week 24 rising
to 64% (14/22) of participants by Week 36. In a cohort that reached
Week 60, 80% (4/5) achieved HDV RNA TND.
These data were presented in an oral session at the American
Association for the Study of Liver Diseases (AASLD) The Liver
Meeting®, in San Diego, CA. Based on these results, and
following a recent meeting with the FDA, Vir Biotechnology plans to
initiate the Phase 3 registrational ECLIPSE program in the first
half of 2025 to further evaluate the combination of tobevibart and
elebsiran for the treatment of CHD.
CHD is a chronic inflammatory liver disease caused by HDV1. It
is the most severe form of chronic viral hepatitis2 and on average,
people living with CHD will progress to cirrhosis and liver failure
within 5 years3. There is no approved treatment in the United
States. The objective of therapy is to clear the virus, and
combination therapy offers the potential to do so by tackling the
viral lifecycle through multiple mechanisms.
“Achieving HDV RNA suppression with a safe, well-tolerated, and
conveniently dosed treatment could be transformative for people
living with hepatitis delta. The impressive rates of virologic
suppression seen in the SOLSTICE Phase 2 data suggest that
tobevibart and elebsiran have the potential to significantly
improve patient outcomes,” said Tarik Asselah, M.D., Ph.D.,
Professor of Hepatology at the Hôpital Beaujon, APHP, Clichy,
France, and at the University of Paris-Cité, and Head of the unit
Viral Hepatitis UMR1149 at INSERM, France. “New, effective
therapeutic options are urgently needed, and I am excited to see
this combination advance into a registrational Phase 3
program.”
Primary Endpoint Analysis from the
Phase 2 SOLSTICE Trial
Clinical trial participants were randomized to receive
tobevibart 300 mg monotherapy every two weeks (n=33) or a
combination of tobevibart 300 mg and elebsiran 200 mg every four
weeks (combination de novo arm, n=32). In addition, the
participants from previous tobevibart or elebsiran monotherapy
cohorts could rollover to receive the combination of tobevibart 300
mg and elebsiran 200 mg every four weeks (combination rollover,
n=13). Rates of virologic suppression were evaluated at Week 24,
and further assessed at Weeks 36, 48 and 60 in those participants
that had reached each timepoint. Further monitoring will continue
up to 192 weeks.
Rapid and Sustained Virologic Suppression – 100% of
participants across combination arms achieved an HDV RNA ≥2 log10
decrease or below limit of detection (LOD) at Week 24, and this
rate was sustained over time in all participants at Weeks 36
(22/22) and those in the rollover cohort that reached Week 60
(5/5).
HDV RNA TND was achieved in 41% (13/32) of participants across
combination arms at Week 24 and this rose to 64% (14/22) at Week
36. By week 60, this had risen further with 80% (4/5) of
participants in the rollover cohort having achieved no detectable
viral RNA.
Approximately 90% of participants receiving the combination
achieved reductions in hepatitis B surface antigen (HBsAg) values
below <10 IU/mL at Week 24, with sustained responses at later
time points. This indicates suppression of the key biologic
mechanisms that HDV requires for viral replication.
ALT Normalization – Alanine aminotransferase (ALT)
decreased in most participants between Day 1 and Week 24 and
normalized in 47% (15/32) of participants in the combination de
novo cohort and 56% (5/9) in the rollover cohort by Week 24. These
rates were sustained at Week 36.
Combined Endpoints – The protocol defined combined
endpoint of HDV RNA decrease ≥ 2 log10 compared to baseline or HDV
RNA below LOD and ALT normalization at Week 24 was observed in 47%
(15/32) of participants in the combination de novo arm.
The more stringent composite endpoint of HDV RNA TND and ALT
normalization was achieved in 19% (6/32) of participants in the
combination de novo arm at Week 24, which increased to 27% (6/22)
by Week 36. This trend was reflected in the combination rollover
cohort in which 33% (3/9) of participants achieved this endpoint at
Week 24 and 40% (2/5) at Week 60. Rates of HDV RNA suppression and
ALT normalization were similar between non-cirrhotic and cirrhotic
participants across combination arms.
Safety Profile – The safety profile of tobevibart and
elebsiran is consistent with previous studies. Treatment-emergent
adverse events (TEAEs) were generally mild or moderate and
transient across all treatment groups, with influenza-like illness
being the most common event. No ALT flares were observed. There
were no study-related discontinuations in the combination arms, and
no treatment-related severe adverse events (SAEs) were
reported.
“People living with hepatitis delta in the US have no approved
treatment options, and therapies are limited globally. At Vir
Biotechnology we are committed to changing that,” said Marianne De
Backer, M.Sc., Ph.D., MBA, Chief Executive Officer, Vir
Biotechnology. “We are confident that our regimen has the potential
to deliver transformative benefits for patients, and we will build
on our strong SOLSTICE data to start our Phase 3 registrational
ECLIPSE program as soon as possible in 2025.”
Phase 3 Registrational ECLIPSE
Program
Following a meeting with the FDA, Vir Biotechnology finalized
the design of the Phase 3 registrational clinical program, ECLIPSE,
which evaluates the tobevibart and elebsiran combination in people
living with CHD. This program, which will commence in the first
half of 2025, will include three randomized, controlled trials
designed to evaluate the combination therapy in comparison to
deferred treatment or bulevirtide. All studies will enroll both
cirrhotic and non-cirrhotic participants. ECLIPSE 1 and 2 are Phase
3 trials designed to provide the registrational efficacy and safety
data needed for submission to global regulatory agencies. ECLIPSE 3
is a Phase 2b trial designed to provide important supportive data,
particularly in Europe, to help establish appropriate pricing and
reimbursement in key markets.
- ECLIPSE 1 will assess the efficacy and safety of tobevibart and
elebsiran compared to deferred treatment in regions such as the
U.S. where bulevirtide is not available or its use is limited.
- ECLIPSE 2 will evaluate the efficacy and safety of switching to
tobevibart and elebsiran in people with CHD who have not achieved
viral suppression with bulevirtide therapy.
- ECLIPSE 3 is a Phase 2b head-to-head trial to evaluate
tobevibart and elebsiran compared with bulevirtide in
bulevirtide-naïve patients.
In June 2024, the U.S. Food and Drug Administration (FDA)
granted fast track designation for the combination of tobevibart
and elebsiran for the treatment of CHD. This designation is
intended to facilitate the development and expedite the review of
drugs to treat serious conditions and fill an unmet medical
need.
Vir Biotechnology announced today that the European Medicines
Agency (EMA) Committee for Orphan Medicinal Products (COMP) issued
a positive opinion on the application for orphan drug designation
of tobevibart and elebsiran for the treatment of CHD. This
designation supports the development of treatments for
life-threatening or chronically debilitating conditions with
significant unmet medical need.
Investor Conference Call
Vir Biotechnology will host an investor conference call on
November 19, 2024 at 5.15 a.m. PT / 8.15 a.m. ET. A live webcast
will be available on https://investors.vir.bio/ and will be
archived on www.vir.bio for 30 days.
About the Phase 2 SOLSTICE Trial
SOLSTICE is a Phase 2 study to evaluate the safety,
tolerability, and efficacy of tobevibart, alone or in combination
with elebsiran, in people with chronic hepatitis delta. This Phase
2 study is a multi-center, open-label, randomized study. Primary
endpoints include proportion of participants with undetectable
hepatitis delta virus (HDV) RNA (defined as HDV RNA equal or
greater than 2 log10 decrease from baseline or below limit of
detection) up to week 24, alanine aminotransferase (ALT)
normalization (defined as ALT below upper limit of normal) up to
week 24, and treatment-emergent adverse events (TEAEs) and serious
adverse events (SAEs) up to 118 weeks. Secondary endpoints include
proportion of participants with undetectable HDV RNA and different
timepoints and up to 192 weeks. More information about this trial
can be found at clinicaltrials.gov (NCT05461170).
About Tobevibart and Elebsiran
Tobevibart is an investigational broadly neutralizing monoclonal
antibody targeting the hepatitis B surface antigen. It is designed
to inhibit the entry of hepatitis B and hepatitis delta viruses
into hepatocytes, and to reduce the level of circulating viral and
subviral particles in the blood. Tobevibart, which incorporates
Xencor’s Xtend™ and other Fc technologies, has been engineered to
have an extended half-life and was identified using Vir
Biotechnology’s proprietary monoclonal antibody discovery platform.
Tobevibart is administered subcutaneously, and it is currently in
clinical development for the treatment of patients with chronic
hepatitis B and patients with chronic hepatitis delta.
Elebsiran is an investigational hepatitis B virus-targeting
small interfering ribonucleic acid (siRNA) designed to degrade
hepatitis B virus RNA transcripts and limit the production of
hepatitis B surface antigen. Current data indicates that it has the
potential to have direct antiviral activity against hepatitis B
virus and hepatitis delta virus. Elebsiran is administered
subcutaneously, and it is currently in clinical development for the
treatment of patients with chronic hepatitis B and patients with
chronic hepatitis delta. It is the first asset in Vir
Biotechnology’s collaboration with Alnylam Pharmaceuticals, Inc. to
enter clinical studies.
Tobevibart and elebsiran are also being evaluated as a potential
functional cure for chronic hepatitis B. Vir Biotechnology recently
presented positive safety and efficacy end-of-treatment results
from the MARCH Phase 2 clinical study evaluating combinations of
tobevibart and elebsiran, alone or in combination with pegylated
interferon alfa (PEG-IFNα), in participants with chronic hepatitis
B in a late-breaker oral presentation at AASLD The Liver
Meeting®.
About Vir Biotechnology, Inc.
Vir Biotechnology, Inc. is a clinical-stage biopharmaceutical
company focused on powering the immune system to transform lives by
discovering and developing medicines for serious infectious
diseases and cancer. It’s clinical-stage portfolio includes
infectious disease programs for chronic hepatitis delta and chronic
hepatitis B infections and programs across several clinically
validated targets in solid tumor indications. Vir Biotechnology
also has a preclinical portfolio of programs across a range of
other infectious diseases and oncologic malignancies. Vir
Biotechnology routinely posts information that may be important to
investors on its website.
References:
1 NIH National Institute of Diabetes and Digestive and Kidney
Diseases Hepatitis D - NIDDK (nih.gov), accessed September 2024 2
WHO Hepatitis Delta Factsheet – Hepatitis D (who.int), accessed
September 2024 3 CDC What is Hepatitis D - FAQ | CDC
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,” “plan,” “potential,” “aim,”
“expect,” “anticipate,” “promising” 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 Biotechnology’s expectations and assumptions as of the
date of this press release. Forward-looking statements contained in
this press release include, but are not limited to, statements
regarding Vir Biotechnology’s strategy and plans, the potential
clinical effects of tobevibart and elebsiran, the potential
benefits, safety and efficacy of tobevibart and elebsiran, the
timing, nature and significance of data from Vir Biotechnology’s
multiple ongoing trials evaluating tobevibart and elebsiran, Vir
Biotechnology’s plans and expectations for its CHD and CHB
programs, and risks and uncertainties associated with drug
development and commercialization. Many factors may cause
differences between current expectations and actual results,
including unexpected safety or efficacy data or results observed
during clinical trials or in data readouts; the occurrence of
adverse safety events; risks of unexpected costs, delays or other
unexpected hurdles; difficulties in collaborating with other
companies; successful development and/or commercialization of
alternative product candidates by Vir Biotechnology’s competitors;
changes in expected or existing competition; delays in or
disruptions to Vir Biotechnology’s business or clinical trials due
to geopolitical changes or other external factors; and unexpected
litigation or other disputes. Drug development and
commercialization involve a high degree of risk, and only a small
number of research and development programs result in
commercialization of a product. Results in early-stage clinical
trials may not be indicative of full results or results from later
stage or larger scale clinical trials and do not ensure regulatory
approval. You should not place undue reliance on these statements,
or the scientific data presented. 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 Biotechnology’s filings with the U.S. Securities and Exchange
Commission, including the section titled “Risk Factors” contained
therein. Except as required by law, Vir Biotechnology assumes no
obligation to update any forward-looking statements contained
herein to reflect any change in expectations, even as new
information becomes available.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20241118939659/en/
Media Arran Attridge Senior Vice President, Corporate
Communications aattridge@vir.bio
Investors Richard Lepke Senior Director, Investor
Relations rlepke@vir.bio
Vir Biotechnology (NASDAQ:VIR)
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