REG - GlaxoSmithKline PLC - Sotrovimab retains its activity vs Omicron variant

GSKAnnouncement

07/12/2021 07:10

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RNS Number : 8046U  GlaxoSmithKline PLC  07 December 2021

 

Issued: 07 December 2021, London UK and San Francisco US

 

Preclinical studies demonstrate sotrovimab retains activity against the full
combination of mutations in the spike protein of the Omicron SARS-CoV-2
variant

·    New preclinical findings generated through in vitro testing of
sotrovimab against the complete pseudo-virus, updated to bioRxiv

·    Data build on promising signal published last week, underscoring the
importance of sotrovimab for early treatment of COVID-19

·    Sotrovimab is authorised and available for the treatment of early
COVID-19 in the US and multiple countries around the world

 

LONDON and SAN FRANCISCO, Dec. XX, 2021 - GlaxoSmithKline plc (LSE/NYSE: GSK)
and Vir Biotechnology, Inc. (Nasdaq: VIR) today announced an update to
preclinical data on bioRxiv 1  (#_ftn1) , a preprint server, demonstrating
that sotrovimab, an investigational monoclonal antibody, retains in vitro
activity against the full known Omicron spike protein, the new SARS-CoV-2
variant (B.1.1.529). The preclinical data was generated through pseudo-virus
testing of the combined known mutations of the Omicron variant, which included
the maximum number of changes (37 mutations) identified to date in the spike
protein. These findings build on the initial preclinical data generated
through pseudo-virus testing, provided last week
(https://www.gsk.com/en-gb/media/press-releases/preclinical-data-demonstrate-sotrovimab-retains-activity-against-key-omicron-mutations-new-sars-cov-2-variant/)
, showing sotrovimab retained in vitro activity against key individual
mutations of the Omicron variant, including those found in the binding site of
sotrovimab. These data add to the growing body of preclinical evidence
demonstrating that sotrovimab retains activity against all tested variants of
concern.

George Scangos, PhD, Chief Executive Officer of Vir, said: "Sotrovimab is the
first monoclonal antibody to report preclinical data demonstrating activity
against all tested SARS-CoV-2 variants of concern and interest to date,
including Omicron, as well as the still prevalent and highly contagious Delta
variant. Given the less than three-fold neutralization shift demonstrated in
the pre-clinical pseudo-virus assay, which falls below the FDA authorized fact
sheet guidance of less than a 5-fold change, we are confident that sotrovimab
will continue to provide significant benefit for the early treatment of
patients hoping to avoid the most severe consequences of COVID-19."

Dr Hal Barron, Chief Scientific Officer and President R&D, GSK, said:
"From the outset of our collaboration with Vir we hypothesized that sotrovimab
would have a high barrier to resistance and thus could deliver best-in-class
potential for the early treatment of patients with COVID-19. These
pre-clinical data demonstrate the potential for our monoclonal antibody to be
effective against the latest variant, Omicron, plus all other variants of
concern defined to date by the WHO, and we look forward to discussing these
results with regulatory authorities around the world."

 

About sotrovimab

Sotrovimab is an investigational SARS-CoV-2 neutralising monoclonal antibody.
The antibody binds to an epitope on SARS-CoV-2 shared with SARS-CoV-1 (the
virus that causes SARS), indicating that the epitope is highly conserved,
which may make it more difficult for resistance to develop. Sotrovimab, which
incorporates Xencor, Inc.'s Xtend™ technology, has also been designed to
achieve high concentration in the lungs to ensure optimal penetration into
airway tissues affected by SARS-CoV-2 and to have an extended half-life.

 

Pre-clinical data, published in bioRxiv, demonstrate that sotrovimab retains
activity against all currently tested variants of concern and interest of the
SARS-CoV-2 virus as defined by WHO, plus others, including but not limited to
Delta (B.1.617.2), Delta Plus (AY.1 or AY.2), Mu (B.1.621) and Omicron
(B.1.1.529).

 

About the sotrovimab clinical development program

·      COMET-ICE: a phase III, multi-centre, double-blind,
placebo-controlled trial investigated an intravenous (IV) infusion of
sotrovimab in adults with mild-to-moderate COVID-19 at high risk of
progression to severe disease, who are not hospitalised and not requiring
oxygen. The final COMET-ICE trial results in the full trial population of
1,057 participants demonstrated a 79% reduction (adjusted relative risk
reduction) (p<0.001) in hospitalisation for more than 24 hours or death due
to any cause by Day 29 compared to placebo, meeting the primary endpoint of
the trial. Interim data were published in The New England Journal of Medicine
(https://www.nejm.org/doi/full/10.1056/NEJMoa2107934) on October 27, 2021, and
final data were pre-published on November 8, 2021, on medRxiv
(https://www.medrxiv.org/content/10.1101/2021.11.03.21265533v1) .

·      COMET-TAIL
(https://www.clinicaltrials.gov/ct2/show/NCT04913675?term=vir-7831&draw=2)
: a phase III, randomised, multi-centre, open-label, non-inferiority trial of
intramuscular (IM) versus IV administration of sotrovimab for the early
treatment of mild-to-moderate COVID-19 in high-risk non-hospitalised adult and
paediatric patients (12 years of age and older). The trial's primary endpoint
was met, and headline data demonstrated that IM administered sotrovimab was
non-inferior and offered similar efficacy to IV administration for high-risk
populations. The companies plan to submit the complete COMET-TAIL data set to
a peer-reviewed journal for publication in the first quarter of 2022.

·      COMET-PEAK: a phase II, randomised, multi-centre, parallel-group
trial evaluating IV and IM administration of sotrovimab in outpatients with
mild-to-moderate COVID-19. Data available to date from open-label Part B of
the trial (500mg IV vs 500mg IM) demonstrated equivalence on the virological
response between the IM and IV arms. The companies plan to submit the complete
COMET-PEAK data set to a peer-reviewed journal for publication in due course.

·      GSK and Vir are also partnering to assess the use of sotrovimab
in uninfected immunocompromised adults to determine whether sotrovimab can
prevent symptomatic COVID-19 infection. GSK and Vir support
investigator-sponsored studies and foster scientific collaborations with
experienced investigators and networks involved in the continuum of care of
immunocompromised patients to understand the role sotrovimab for prophylaxis
could play in this population. Discussions with regulatory authorities
regarding the prophylaxis program will occur in due course.

 

About global access to sotrovimab

Sotrovimab is authorised for emergency use in the United States. Xevudy
(sotrovimab) received a positive scientific opinion
(https://www.ema.europa.eu/en/news/ema-issues-advice-use-sotrovimab-vir-7831-treating-covid-19)
 under Article 5(3) of Regulation 726/2004 from the Committee for Human
Medicinal Products in the EU, conditional marketing authorisation by the UK
Medicines and Healthcare Products Regulatory Agency, provisional marketing
authorisation in Australia, and conditional marketing authorisation in Saudi
Arabia. It has been approved via the Special Approval for Emergency Pathway in
Japan. Temporary authorisations for sotrovimab have been granted in a dozen
countries.

 

GSK and Vir also recently submitted the Marketing Authorisation Application to
the European Medicines Agency for Xevudy for the treatment of adults and
adolescents (aged 12 years and over and weighing at least 40kg) with
coronavirus disease 2019 (COVID-19) who do not require oxygen supplementation
and who are at risk of progressing to severe COVID-19.

 

Sotrovimab is supplied in several countries worldwide, including through
national agreements in the United States, United Kingdom, Japan, Australia,
Canada, Singapore, Switzerland, and the United Arab Emirates. The companies
have also signed a Joint Procurement Agreement with the European Commission to
supply doses of sotrovimab. Additional agreements are yet to be announced due
to confidentiality or regulatory requirements.

 

Sotrovimab in the United States

The following is a summary of information for sotrovimab. Healthcare providers
in the US should review the Fact Sheets for information about the authorized
use of sotrovimab and mandatory requirements of the EUA. Please see the Food
and Drug Administration (FDA) Letter of Authorization
(https://www.sotrovimab.com/content/dam/cf-pharma/hcp-sotrovimab-phase2/en_US/sotrovimab-fda-letter-of-authorization.pdf)
, full Fact Sheet for Healthcare Providers
(https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Sotrovimab/pdf/SOTROVIMAB-EUA.PDF#nameddest=HCPFS)
and full Fact Sheet for Patients, Parents, and Caregivers
(https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Sotrovimab/pdf/SOTROVIMAB-PATIENT-FACT-SHEET.PDF)
.

Sotrovimab has been authorized by the US FDA for the emergency use described
below. Sotrovimab is not FDA-approved for this use.

 

Sotrovimab is authorized only for the duration of the declaration that
circumstances exist justifying the authorization of the emergency use of
sotrovimab under section 564(b)(1) of the Act, 21 U.S.C. § 360bbb-3(b)(1),
unless the authorization is terminated or revoked sooner.

 

Authorized Use

The U.S. FDA has issued an Emergency Use Authorization (EUA) to permit the
emergency use of the unapproved product sotrovimab for the treatment of
mild-to-moderate coronavirus disease 2019 (COVID-19) in adults and pediatric
patients (12 years of age and older weighing at least 40 kg) with positive
results of direct SARS-CoV-2 viral testing, and who are at high risk for
progression to severe COVID-19, including hospitalization or death.

 

Limitations of Authorized Use

Sotrovimab is not authorized for use in patients:

·      who are hospitalized due to COVID-19, OR

·      who require oxygen therapy due to COVID-19, OR

·      who require an increase in baseline oxygen flow rate due to
COVID-19 (in those on chronic oxygen therapy due to underlying non-COVID-19
related comorbidity)

 

Benefit of treatment with sotrovimab has not been observed in patients
hospitalized due to COVID‑19. SARS-CoV-2 monoclonal antibodies may be
associated with worse clinical outcomes when administered to hospitalized
patients with COVID‑19 requiring high flow oxygen or mechanical ventilation.

 

Important Safety Information

 

CONTRAINDICATIONS

Sotrovimab is contraindicated in patients who have a history of anaphylaxis to
sotrovimab or to any of the excipients in the formulation.

 

WARNINGS AND PRECAUTIONS

There are limited clinical data available for sotrovimab. Serious and
unexpected adverse events may occur that have not been previously reported
with sotrovimab use.

 

Hypersensitivity Including Anaphylaxis and Infusion-Related Reactions

Serious hypersensitivity reactions, including anaphylaxis, have been observed
with administration of sotrovimab. If signs and symptoms of a clinically
significant hypersensitivity reaction or anaphylaxis occur, immediately
discontinue administration and initiate appropriate medications and/or
supportive care.

 

Infusion-related reactions, occurring during the infusion and up to 24 hours
after the infusion, have been observed with administration of sotrovimab.
These reactions may be severe or life threatening.

 

Signs and symptoms of infusion-related reactions may include: fever,
difficulty breathing, reduced oxygen saturation, chills, fatigue, arrhythmia
(e.g., atrial fibrillation, sinus tachycardia, bradycardia), chest pain or
discomfort, weakness, altered mental status, nausea, headache, bronchospasm,
hypotension, hypertension, angioedema, throat irritation, rash including
urticaria, pruritus, myalgia, vaso-vagal reactions (e.g., pre-syncope,
syncope), dizziness and diaphoresis.

 

Consider slowing or stopping the infusion and administer appropriate
medications and/or supportive care if an infusion-related reaction occurs.

 

Hypersensitivity reactions occurring more than 24 hours after the infusion
have also been reported with the use of SARS-CoV-2 monoclonal antibodies under
Emergency Use Authorization.

 

Clinical Worsening After SARS-CoV-2 Monoclonal Antibody Administration

Clinical worsening of COVID‑19 after administration of SARS-CoV-2 monoclonal
antibody treatment has been reported and may include signs or symptoms of
fever, hypoxia or increased respiratory difficulty, arrhythmia (e.g., atrial
fibrillation, tachycardia, bradycardia), fatigue and altered mental status.
Some of these events required hospitalization. It is not known if these events
were related to SARS-CoV-2 monoclonal antibody use or were due to progression
of COVID‑19.

 

Limitations of Benefit and Potential for Risk in Patients with Severe
COVID‑19

Benefit of treatment with sotrovimab has not been observed in patients
hospitalized due to COVID‑19. SARS-CoV-2 monoclonal antibodies may be
associated with worse clinical outcomes when administered to hospitalized
patients with COVID‑19 requiring high flow oxygen or mechanical ventilation.
Therefore, sotrovimab is not authorized for use in patients: who are
hospitalized due to COVID‑19, OR who require oxygen therapy due to
COVID‑19 OR who require an increase in baseline oxygen flow rate due to
COVID‑19 in those on chronic oxygen therapy due to underlying
non‑COVID‑19 related comorbidity.

 

ADVERSE EVENTS

Hypersensitivity adverse reactions have been observed in 2% of patients
treated with sotrovimab and 1% with placebo in COMET-ICE.

 

The most common treatment-emergent adverse events observed in the sotrovimab
treatment group in COMET-ICE were rash (1%) and diarrhea (2%), all of which
were Grade 1 (mild) or Grade 2 (moderate). No other treatment-emergent adverse
events were reported at a higher rate with sotrovimab compared to placebo.

 

USE IN SPECIFIC POPULATIONS

 

Pregnancy

There are insufficient data to evaluate a drug-associated risk of major birth
defects, miscarriage or adverse maternal or fetal outcome. Sotrovimab should
be used during pregnancy only if the potential benefit justifies the potential
risk for the mother and the fetus.

 

Lactation

There are no available data on the presence of sotrovimab in human milk, the
effects on the breastfed infant or the effects on milk production. Individuals
with COVID-19 who are breastfeeding should follow practices according to
clinical guidelines to avoid exposing the infant to COVID-19.

 
About the GSK and Vir collaboration

In April 2020, Vir and GSK entered into a collaboration to research and
develop solutions for coronaviruses, including SARS-CoV-2, the virus that
causes COVID-19. The collaboration uses Vir's proprietary monoclonal antibody
platform technology to accelerate existing and identify new anti-viral
antibodies that could be used as therapeutic or preventive options to help
address the current COVID-19 pandemic and future outbreaks. The companies will
leverage GSK's expertise in functional genomics and combine their capabilities
in CRISPR screening and artificial intelligence to identify anti-coronavirus
compounds that target cellular host genes. They will also apply their combined
expertise to research SARS-CoV-2 and other coronavirus vaccines.

 

GSK commitment to tackling COVID-19

GSK's response to COVID-19 has been one of the broadest in the industry, with
potential treatments in addition to our vaccine candidates in development with
partner organisations.

 

GSK is collaborating with several organisations on COVID-19 vaccines by
providing access to our adjuvant technology. We are working with Sanofi SA,
Medicago Inc. and SK bioscience Co., Ltd. to develop adjuvanted,
protein-based vaccine candidates, and all are now in phase III clinical
trials. The use of an adjuvant can be of particular importance in a pandemic
since it may reduce the amount of vaccine protein required per dose, allowing
more vaccine doses to be produced and contributing to protecting more people
in need.

 

GSK is also working with mRNA specialist, CureVac NV, to jointly develop
next-generation, optimised mRNA vaccines for COVID-19 with the potential to
address multiple emerging variants in one vaccine.

 

GSK is also exploring treatments for COVID-19 patients, collaborating with Vir
Biotechnology to investigate monoclonal antibodies that could be used as
therapeutic or preventive options for COVID-19.

 

Vir's commitment to COVID-19

Vir was founded with the mission of addressing the world's most serious
infectious diseases. In 2020, Vir responded rapidly to the COVID-19 pandemic
by leveraging our unique scientific insights and industry-leading antibody
platform to explore multiple monoclonal antibodies as potential therapeutic or
preventive options for COVID-19. Sotrovimab is the first SARS-CoV-2-targeting
antibody Vir advanced into the clinic. It was carefully selected for its
demonstrated promise in preclinical research, including an anticipated high
barrier to resistance and potential ability to both block the virus from
entering healthy cells and clear infected cells. Vir is continuing to pursue
novel therapeutic and prophylactic solutions to combat SARS-CoV-2 and future
coronavirus pandemics, both independently and in collaboration with its
partners.

 

About GSK

GSK is a science-led global healthcare company. For further information please
visit www.gsk.com/aboutus (https://www.gsk.com/en-gb/about-us/) .

 

 

About Vir Biotechnology

Vir Biotechnology is a commercial-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 COVID-19,
hepatitis B virus, influenza A and human immunodeficiency virus. For more
information, please visit www.vir.bio (http://www.vir.bio/) .

 

Reference

(1)Cathcart AL, Havenar-Daughton C, Lempp FA, et al. The dual function
monoclonal antibodies VIR-7831 and VIR-7832 demonstrate potent in vitro and in
vivo activity against SARS-CoV-2. bioRxiv
(https://www.biorxiv.org/content/10.1101/2021.03.09.434607v8) . 2021. Updated
manuscript submitted and online pre-print publication pending.

 

 

 GSK inquiries:

 Media inquiries:             Tim Foley          +44 (0) 20 8047 5502  (London)
                              Madeleine Breckon  +44 (0) 20 8047 5502  (London)
                              Kristen Neese      +1 804 217 8147       (Philadelphia)
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 Analyst/Investor inquiries:  Nick Stone         +44 (0) 7717 618834   (London)
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                              James Dodwell      +44 (0) 20 8047 2406  (London)
                              Mick Readey        +44 (0) 7990 339653   (London)
                              Jeff McLaughlin    +1 215 751 7002       (Philadelphia)
                              Frannie DeFranco   +1 215 751 4855       (Philadelphia)

 

 

Vir Biotechnology Contacts:

Heather Rowe Armstrong                      Cara Miller

VP, Investor Relations                           VP,
Corporate Communications

harmstrong@vir.bio
cmiller@vir.bio

+1 415 915 4228
  +1 415 941 6746

 

 

GSK cautionary statement regarding forward-looking statements

GSK cautions investors that any forward-looking statements or projections made
by GSK, including those made in this announcement, are subject to risks and
uncertainties that may cause actual results to differ materially from those
projected. Such factors include, but are not limited to, those described in
the Company's Annual Report on Form 20-F for 2020, GSK's Q3 Results and any
impacts of the COVID-19 pandemic.

 

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," "plan," "potential," "aim," "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'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 the
ability of sotrovimab to treat and/or prevent COVID-19 either through IV or IM
administration, Vir's collaboration with GSK, plans to progress regulatory
submissions globally, including with the FDA regarding the existing EUA for
sotrovimab, planned discussions with other global regulatory agencies, the
timing of availability of clinical data, program updates and data disclosures,
the clinical development program for sotrovimab, and the ability of sotrovimab
to maintain activity against circulating variants of concern and interest,
including Omicron. Many factors may cause differences between current
expectations and actual results, including unexpected safety or efficacy data
observed during preclinical or clinical studies, challenges in the treatment
of hospitalized patients, difficulties in collaborating with other companies
or government agencies, challenges in accessing manufacturing capacity,
successful development and/or commercialization of alternative product
candidates by Vir's competitors, changes in expected or existing competition,
delays in or disruptions to Vir's business or clinical trials due to the
COVID-19 pandemic, geopolitical changes or other external factors, 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.

 

 

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 1  (#_ftnref1)  Cathcart AL, Havenar-Daughton C, Lempp FA, et al. The dual
function monoclonal antibodies VIR-7831 and VIR-7832 demonstrate potent in
vitro and in vivo activity against SARS-CoV-2. bioRxiv. 2021. Updated
manuscript submitted and online pre-print publication pending.

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