REG - GlaxoSmithKline PLC - Phase III IM administration data for sotrovimab

GSKAnnouncement

12/11/2021 12:00

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RNS Number : 2554S  GlaxoSmithKline PLC  12 November 2021

Issued: 12 November 2021, London UK and San Francisco, U.S.

 

Primary endpoint met in COMET-TAIL Phase III trial evaluating intramuscular
administration of sotrovimab for early treatment of COVID-19

 

·   COMET-TAIL Phase III data demonstrated that intramuscular
administration of sotrovimab was non-inferior and offered similar efficacy to
intravenous administration for high-risk populations

·    The trial enrolled participants during the Delta variant wave of the
pandemic in the US

 

 

GlaxoSmithKline plc (LSE/NYSE: GSK) and Vir Biotechnology, Inc. (Vir) (Nasdaq:
VIR) today announced headline data from the randomised, multi-centre,
open-label COMET-TAIL Phase III trial, which achieved its primary endpoint,
demonstrating intramuscular (IM) administration of sotrovimab was non-inferior
to intravenous (IV) administration for the early treatment of mild-to-moderate
COVID-19 in high-risk, non-hospitalised adults and adolescents (12 years of
age and older).

The COMET-TAIL Phase III trial was designed to evaluate the efficacy, safety,
and tolerability of sotrovimab delivered via IM administration compared to IV
administration in high-risk patients up to seven days after symptom onset. In
the IM administration (500mg) arm of the trial, there was a 2.7% rate of
progression to hospitalisation for more than 24 hours or death through Day 29
of the trial, compared to 1.3% in the IV administration arm (also 500mg). The
adjusted difference between the IM and IV arms of the trial was 1.07% with a
95% confidence interval (CI) of -1.25% to 3.39%. The upper bound of the 95% CI
is within the predetermined 3.5% non-inferiority margin set for the trial's
primary endpoint in consultation with the US Food and Drug Administration
(FDA).

In addition, there were low rates of serious adverse events and Grade 3-4
adverse events (≤1% in both arms, for both measures) observed in the
headline data.

The companies plan to progress regulatory submissions globally, including
ongoing discussions with the FDA regarding the existing Emergency Use
Authorization for sotrovimab.

Dr Hal Barron, Chief Scientific Officer and President, said: "I am pleased
that today's results demonstrated similar efficacy for sotrovimab when
injected directly into the muscle compared to administered intravenously,
potentially offering a more convenient option for patients. We look forward to
working with regulatory authorities to help make this new option available to
appropriate patients with COVID-19."

George Scangos, Ph.D., chief executive officer of Vir, said: "This trial was
conducted during the height of circulation of the Delta variant, with
significant enrollment in Florida - a hot spot for this particular variant and
where hospitalisation rates averaged more than 10 percent of confirmed cases.
We designed sotrovimab to stand up to the variants that we anticipated would
occur, and these data demonstrate that sotrovimab administered via IV or IM
could prove important in the fight against COVID-19 following authorisation.
As we approach the third year of the pandemic, we can expect that multiple
treatment options will continue to be needed, particularly for high-risk
patients with complex health needs."

Today's update follows announcements in the first half of 2021 regarding the
COMET-ICE Phase III trial, which investigated IV infusion of sotrovimab in
adults with mild or moderate COVID-19 at high-risk of progression to severe
disease. The final COMET-ICE trial results in the full study population of
1057 participants, demonstrated a 79% reduction in hospitalisation and death
at Day 29 vs placebo.

 

 

 

 

 

About sotrovimab

Sotrovimab is an investigational SARS-CoV-2 neutralising monoclonal antibody.
The antibody binds to an epitope on SARS-CoV-2 that is 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'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.

 

Updated in vitro data, published in bioRxiv
(https://www.biorxiv.org/content/10.1101/2021.03.09.434607v7.full.pdf) ,
demonstrate that sotrovimab retains activity against all current variants of
concern and interest of the SARS-CoV-2 virus as defined by the World Health
Organisation, plus others, including, but not limited to, Delta (B.1.617.2),
Delta Plus (AY.1 or AY.2) and Mu (B.1.621).

 

About the sotrovimab clinical development programme

·      COMET-ICE: a Phase III, multi-centre, double-blind,
placebo-controlled trial investigated 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 intravenous (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 intramuscularly
administered sotrovimab was non-inferior and offered similar efficacy to
intravenous administration for high-risk populations. The COMET-TAIL trial
enrolled a total of 983 patients up to seven days after onset of symptoms. The
trial originally included three arms: 500mg of sotrovimab given intravenously,
and two intramuscular arms, consisting of 500mg and a low dose of 250mg. An
independent safety monitoring committee recommended enrolment in the 250mg arm
be discontinued after a greater number of hospitalisations in that arm was
noted. The 500mg dose arms were recommended to continue with enrolment as
planned. The companies plan to submit the full 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, while also showing an acceptable
tolerability profile for IM with only 10/82 participants (12%) reporting any
injection site reaction, all of which were low grade (Grade 1). The companies
plan to submit the full COMET-PEAK data set to a peer-reviewed journal for
publication.

·      GSK and Vir are also partnering to investigate the use of
sotrovimab in uninfected immunocompromised adults to determine whether
sotrovimab can prevent symptomatic COVID-19 infection. GSK and Vir are
supporting investigator sponsored studies and fostering scientific
collaborations with both experienced investigators and networks, who are
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 take place
in due course.

 

About global access to sotrovimab

·      Sotrovimab is authorised for emergency use in the United States
and 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 (CHMP) in the EU. Sotrovimab has been granted a provisional
marketing authorisation in Australia and a conditional marketing authorisation
in Saudi Arabia. In Japan it has been approved via the Special Approval for
Emergency Pathway. Temporary authorisations have been granted in Bahrain,
Brazil, Canada, Egypt, Italy, Kuwait, Oman, Qatar, Singapore, Switzerland,
Thailand and the United Arab Emirates.

·      Sotrovimab is supplied in several countries around the world,
including through national agreements in the United States, Japan, Australia,
Canada, Singapore and UAE. We 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 U.S. should review the Fact Sheets for information about the authorised
use of sotrovimab and mandatory requirements of the EUA. Please see the FDA
Letter of Authorisation
(https://www.sotrovimab.com/content/dam/cf-pharma/hcp-sotrovimab/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 U.S. 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. Food and Drug Administration (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
(eg, 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 (eg, 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 (eg, 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 Vir and GSK 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,
Medicago and SK bioscience 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 protect more people in need.

 

GSK is also working with mRNA specialist, CureVac, 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 SARSCoV-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/about-us (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/) .

 

 GSK enquiries:
 Media enquiries:             Tim Foley                        +44 (0) 20 8047 5502  (London)
                              Simon Moore / Madeleine Breckon  +44 (0) 20 8047 5502  (London)
                              Kristen Neese                    +1 804 217 8147       (Philadelphia)
                              Kathleen Quinn                   +1 202 603 5003       (Washington DC)

 Analyst/Investor enquiries:  Nick Stone                       +44 (0) 7717 618834   (London)
                              Sonya Ghobrial                   +44 (0) 7392 784784   (Consumer)
                              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.
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.

 

Registered in England & Wales:

No. 3888792

 

Registered Office:

980 Great West Road

Brentford, Middlesex

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