a9137b
FORM 6-K
SECURITIES
AND EXCHANGE COMMISSION
Washington,
D.C. 20549
Report
of Foreign Issuer
Pursuant
to Rule 13a-16 or 15d-16 of
the
Securities Exchange Act of 1934
For the
month of June 2021
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
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United
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Update on AZD7442 STORM CHASER trial
15 June 2021 07:00 BST
Update on AZD7442 STORM CHASER trial
in post-exposure prevention of symptomatic COVID-19
AstraZeneca today announced results from the STORM CHASER trial
assessing the safety and efficacy of AZD7442, a long-acting
antibody (LAAB) combination, for the prevention of symptomatic
COVID-19 in participants recently exposed to the SARS-CoV-2 virus.
The trial did not meet the primary endpoint of post-exposure
prevention of symptomatic COVID-19 with AZD7442 compared to
placebo.
Trial participants were unvaccinated adults 18 years and over with
confirmed exposure to a person with a case of the SARS-CoV-2 virus
within the past eight days. In the overall trial population,
AZD7442 reduced the risk of developing symptomatic COVID-19 by 33%
(95% confidence interval (CI): -26, 65) compared to placebo, which
was not statistically significant (Table 1).
The trial included 1,121 participants in a 2:1 randomisation
AZD7442 to placebo, with 23 cases of symptomatic COVID-19 accrued
in the AZD7442 arm (23/749) and 17 cases accrued in the placebo arm
(17/372). All participants had a negative SARS-CoV-2 antibody
test on the day of dosing to exclude prior infection, and a
nasopharyngeal swab was also collected and subsequently analysed
for SARS-CoV-2 by RT-PCR to detect virus.
Given the importance of finding therapies for COVID-19 and to help
interpret trial results during the pandemic, additional analyses
were performed and are being communicated (Table 1).
In a pre-planned analysis of SARS-CoV-2 PCR positive (detectable
virus) and PCR negative (no detectable virus) participants, AZD7442
reduced the risk of developing symptomatic COVID-19 by 73% (95% CI:
27, 90) compared with placebo, in participants who were PCR
negative at time of dosing. In a post-hoc analysis, in participants
who were PCR negative at baseline, AZD7442 reduced the risk of
developing symptomatic COVID-19 by 92% (95% CI: 32, 99) versus
placebo more than seven days following dosing, and by 51% (95% CI:
-71, 86) up to seven days following dosing.
Myron J. Levin, MD, Professor of Pediatrics and Medicine,
University of Colorado School of Medicine, US, and principal
investigator on the trial, said: "The results of STORM CHASER
suggest that AZD7442 may be useful in preventing symptomatic
COVID-19 in individuals not already infected. The PROVENT trial
will give us more clarity in this patient population. While
COVID-19 vaccination efforts have been successful, there is still a
significant need for prevention and treatment options for certain
populations, including those unable to be vaccinated or those who
may have an inadequate response to vaccination."
Mene Pangalos, Executive Vice President, BioPharmaceuticals
R&D, said: "While this trial did not meet the primary endpoint
against symptomatic illness, we are encouraged by the protection
seen in the PCR negative participants following treatment with
AZD7442. We await results from PROVENT, our pre-exposure prevention
trial and TACKLE, our treatment trial in preventing more severe
disease, to understand the potential role of AZD7442 in protecting
against COVID-19."
Table 1: STORM CHASER analyses
|
Baseline subgroup
|
Onset of case post dose
|
Number of cases / number of participants
|
Relative risk reduction (95% confidence interval)
|
AZD7442 (300mg IM)
|
Placebo
|
All participants(Primary analysis)
|
All cases
|
23 / 749
|
17 / 372
|
33% reductiona
(-26 to 65)
|
PCR-negativeb(Pre-planned
subgroup analysis)
|
All cases
|
6 / 715
|
11 / 358
|
73% reduction (27 to 90)
|
PCR-negativeb(Post
hoc subgroup analysis)
|
≤7 days
|
5 / 715
|
5 / 358
|
51% reduction (-71 to 86)
|
>7
days
|
1 / 710
|
6 / 353
|
92% reduction (32 to 99)
|
a: Not statistically significant.
b: Includes 974 participants (15 cases) confirmed PCR negative at
baseline and 99 participants (2 cases) with PCR status missing at
baseline.
48 participants were confirmed PCR positive at baseline with 23
cases (AZD7442: 17/34; placebo: 6/14).
|
AZD7442 was well tolerated in the trial. Preliminary analyses show
similar adverse events in the placebo and treatment
arms.
Full results from STORM CHASER will be submitted for publication in
a peer-reviewed medical journal and presented at a forthcoming
medical meeting.
Financial considerations
On 16 March 2021, AstraZeneca announced an
extended agreement with the US Government to supply up to 500,000
additional doses of AZD7442 for $205m, contingent on AZD7442
receiving Food and Drug Administration Emergency Use Authorisation
in post-exposure prophylaxis. Discussions regarding next steps with
the US Government are ongoing.
STORM CHASER
STORM CHASER is a Phase III, randomised, double-blind,
placebo-controlled, multi-centre trial assessing the safety and
efficacy of a single 300mg dose of AZD7442 compared to placebo for
the post-exposure prevention of COVID-19. The trial was conducted
in 59 sites in the UK and US. 1,121 participants were randomised in
a 2:1 ratio to receive a single intramuscular (IM) dose of either
300mg of AZD7442 (n=749) or saline placebo (n=372), administered in
two separate, sequential IM injections. The primary efficacy
endpoint is the first case of SARS-CoV-2 RT-PCR-positive
symptomatic illness occurring post dose to Day 183. The primary
analysis was to be conducted 30 days after 25 events meeting the
primary efficacy endpoint definition had occurred. This primary
analysis includes data and additional events accumulated up to 7
April 2021, 30 days after the symptom assessment date of the 25th
event; participants will continue to be followed for 15
months.
The post hoc analysis looked at cases of symptomatic COVID-19 in
the PCR-negative group occurring seven days or less after dosing
and more than seven days after dosing. This was based on the known
incubation period of SARS-CoV-2. Cases occurring more than seven
days after dosing are likely to be due to infection that occurred
after dosing rather than before.1
Participants were adults 18 years and over with potential exposure,
within eight days, to a specific identified individual with
laboratory-confirmed SARS-CoV-2 virus, symptomatic or asymptomatic,
and who were therefore assessed at the time of enrolment to be at
appreciable risk of imminently developing COVID-19. Such
individuals included, but were not limited to, those who shared a
household, those living in institutional residences (military
lodging, dormitories, etc.), health care workers, long-term care
facility workers, and workers in occupational or industrial
settings in which close contact is common.
AZD7442
AZD7442 is a combination of two LAABs - tixagevimab (AZD8895)
and cilgavimab (AZD1061) - derived from B cells donated by
convalescent patients after SARS-CoV-2 virus. Discovered by
Vanderbilt University Medical Center and licensed to
AstraZeneca in June 2020, the
human monoclonal antibodies bind to distinct sites on the
SARS-CoV-2 spike protein2 and
were optimised by AstraZeneca with half-life extension and reduced
Fc receptor binding. The half-life extension approximately triples
the durability of its action compared to conventional antibodies
and could afford six to 12 months of protection from COVID-19
following a single administration.3-6 The
reduced Fc receptor binding aims to minimise the risk of
antibody-dependent enhancement of disease - a phenomenon in which
virus-specific antibodies promote, rather than inhibit, infection
and/or disease.7
AZD7442 is currently being tested in several additional COVID-19
prevention and treatment trials: PROVENT8 Phase
III trial of over 5,000 participants in pre-exposure
prophylaxis; TACKLE
COVID-199 Phase
III treatment trial in outpatient setting; and collaborator
treatment trials in outpatient and hospitalised settings. AZD7442
is being assessed in both IM and intravenous administration
routes.
AZD7442 is being developed with support from the US Government,
including federal funds from the Department of Health and Human
Services; Office of the Assistant Secretary for Preparedness and
Response; Biomedical Advanced Research and Development Authority in
partnership with the Department of Defense; Joint Program Executive
Office for Chemical, Biological, Radiological and Nuclear Defense;
under Contract No. W911QY-21-9-0001.
Preliminary 'in vitro' findings from investigators at Oxford
University and Columbia University also demonstrate that AZD7442
neutralises recent emergent SARS-CoV-2 viral
variants.10-14
Data published in Nature in
July 2020 showed that in pre-clinical experiments, the LAABs were
able to block the binding of the SARS-CoV-2 virus to host cells and
protect against infection in cell and animal models of
disease.15
Under the terms of the licensing agreement with Vanderbilt,
AstraZeneca will pay single-digit royalties on future net
sales.
AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led
biopharmaceutical company that focuses on the discovery,
development and commercialisation of prescription medicines in
Oncology and BioPharmaceuticals, including Cardiovascular, Renal
& Metabolism, and Respiratory & Immunology. Based in
Cambridge, UK, AstraZeneca operates in over 100 countries and its
innovative medicines are used by millions of patients worldwide.
Please visit astrazeneca.com and follow the Company on Twitter
@AstraZeneca.
Contacts
For details on how to contact the Investor Relations Team, please
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For Media contacts, click here.
References
1. Guan WJ, et al. Clinical
Characteristics of Coronavirus Disease 2019 in
China. N Engl J
Med. 2020;382(18):1708. Epub
2020 Feb 28.
2. Dong J, et al. Genetic and
structural basis for recognition of SARS-CoV-2 spike protein by a
two-antibody cocktail. bioRxiv. 2021; doi:
10.1101/2021.01.27.428529.
3. Robbie GJ, et al. A novel
investigational Fc-modified humanized monoclonal antibody,
motavizumab-YTE, has an extended half-life in healthy
adults. Antimicrob Agents
Chemother.
2013;57:6147-53.
4. Griffin MP, et al. Safety,
Tolerability, and Pharmacokinetics of MEDI8897, the Respiratory
Syncytial Virus Prefusion F-Targeting Monoclonal Antibody with an
Extended Half-Life, in Healthy Adults. Antimicrob Agents
Chemother. 2017;61:e01714-16.
5. Yu XQ, et al. Safety, Tolerability,
and Pharmacokinetics of MEDI4893, an Investigational,
Extended-Half-Life, Anti-Staphylococcus aureus Alpha-Toxin Human
Monoclonal Antibody, in Healthy Adults. Antimicrob Agents
Chemother.
2016;61:e01020-16.
6. Domachowske JB, et al. Safety,
Tolerability and Pharmacokinetics of MEDI8897, an Extended
Half-life Single-dose Respiratory Syncytial Virus Prefusion
F-targeting Monoclonal Antibody Administered as a Single Dose to
Healthy Preterm Infants. Pediatr Infect Dis
J.
2018;37:886-892.
Dejnirattisai W, et al. Antibody
evasion by the Brazilian P.1 strain of
SARS-CoV-2. bioRxiv.
2021; https://doi.org/10.1101/2021.03.12.435194.
7. van Erp EA, et
al. Fc-Mediated Antibody Effector Functions During Respiratory
Syncytial Virus Infection and Disease. Front
Immunol. 2019; 10:
548.
8. Clinicaltrials.gov.
Phase III Double-blind, Placebo-controlled Study of AZD7442 for
Pre-exposure Prophylaxis of COVID-19 in Adult.
(PROVENT). Available at: https://clinicaltrials.gov/ct2/show//NCT04625725.
[Last accessed: 7 April 2021].
9. Clinicaltrials.gov.
Phase III Study of AZD7442 for Treatment
of COVID-19 in Outpatient Adults (TACKLE). Available
at: https://clinicaltrials.gov/ct2/show//NCT04723394.
[Last accessed: 7 April 2021].
10. Zhou D, et al. Evidence of escape
of SARS-CoV-2 variant B.1.351 from natural and vaccine induced
sera. Cell. 2021; 184 (9): 2348-2361.e6.
11. Dejnirattisai W,
et al. Antibody evasion by the Brazilian P.1 strain of
SARS-CoV-2. bioRxiv.
2021; https://doi.org/10.1101/2021.03.12.435194.
12. Wang P, et al. Antibody
resistance of SARS-CoV-2 variants B.1.351 and
B.1.1.7. Nature 2021;593:130-135.
13. Chen RE, et al. Resistance of
SARS-CoV-2 variants to neutralization by monoclonal and
serum-derived polyclonal antibodies. Nat Med 2021; 27, 717-726.
https://doi.org/10.1038/s41591-021-01294-w.
14. Wang
P, Nair MS, Liu L. et al. Antibody resistance of
SARS-CoV-2 variants B.1.351 and B.1.1.7. Nature 2021
Mar 8. doi: 10.1038/s41586-021-03398-2. Epub ahead
of print. PMID: 33684923.
15. Zost SJ, et al. Potently
neutralizing and protective human antibodies against SARS-CoV
2. Nature. 2020;584:443-449.
Adrian Kemp
Company Secretary
AstraZeneca PLC
SIGNATURES
Pursuant
to the requirements of the Securities Exchange Act of 1934, the
Registrant has duly caused this report to be signed on its behalf
by the undersigned, thereunto duly authorized.
Date:
15 June
2021
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By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
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