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 April 2021
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
Cambridge
CB2 0AA
United
Kingdom
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Nirsevimab MELODY Phase III trial met primary endpoint of reducing
RSV lower respiratory tract infections in healthy
infants
26 April 2021 07:00 BST
Nirsevimab MELODY Phase III trial met primary endpoint of reducing
RSV lower respiratory tract infections in healthy
infants
First potential passive immunisation to show protection against RSV
in the general infant population
The MELODY Phase III trial for nirsevimab met its primary endpoint
of a statistically significant reduction in the incidence of
medically attended lower respiratory tract infections (LRTI) caused
by respiratory syncytial virus (RSV) compared to
placebo in healthy late preterm and term infants (35 weeks or
more) during their first RSV season.1
Nirsevimab is a long-acting antibody, using AstraZeneca's
proprietary YTE technology, and being developed by AstraZeneca and
Sanofi, with the potential to provide immunity directly to infants
and offer immediate protection against RSV. It is the first
potential immunisation to show protection against RSV in the
general infant population in a Phase III trial.
Preliminary analysis of the safety profile for nirsevimab was
consistent with previous trial data. No clinically meaningful
differences in safety results between the nirsevimab and placebo
groups have been seen.1
RSV is a very common, contagious pathogen that causes seasonal
epidemics of LRTI, including bronchiolitis and
pneumonia.2-4 It
is the leading cause of hospitalisations in infants
worldwide.4
Dr William Muller, Associate Professor, Pediatrics, Northwestern
University Feinberg School of Medicine and Scientific Director,
Clinical and Community Trials, Ann & Robert H. Lurie Children's
Hospital of Chicago, Illinois, US and primary investigator of the
MELODY Phase III trial, said: "Despite respiratory syncytial virus
being the leading cause of pneumonia and bronchiolitis in the first
year of life, there is no routine preventative option currently
approved for all infants. These exciting trial data demonstrate the
potential for nirsevimab to change the prevention landscape not
only by providing protection to a broad population of infants
across the full respiratory syncytial virus season, but also by
achieving this with a single dose."
Mene Pangalos, Executive Vice President, BioPharmaceuticals
R&D, said: "These ground-breaking results mark a major
scientific advancement in our effort to provide protection against
respiratory syncytial virus for all infants. Nearly all children
will contract the virus before age two, leading to nearly 30
million acute lower respiratory tract infections globally each
year. Nirsevimab has the potential to provide a significant public
health benefit as the first respiratory syncytial virus
immunisation for the general infant population, and these data
bring us one step closer to delivering nirsevimab to infants
worldwide."
Jean-Franois Toussaint, Global Head of Research and Development,
Sanofi Pasteur, said: "Respiratory syncytial virus is the leading
cause of hospitalisations in all infants. In fact, most
hospitalisations occur in otherwise healthy infants born at term.
ItÕs clear all infants need protection from this virus, and we
hope nirsevimab becomes an important addition to routine
immunisation schedules."
The evaluation of the primary efficacy endpoint in the MELODY trial
was conducted earlier than anticipated. Global public health
measures to control COVID-19 have reduced the circulation of all
respiratory viruses, including RSV. Sufficient cases had been
accrued prior to the pandemic to evaluate nirsevimab's ability to
prevent RSV LRTI versus placebo. The trial is ongoing to collect
additional safety data. Results from the MELODY trial will be
presented at a forthcoming medical meeting.
Nirsevimab is also being evaluated in the MEDLEY Phase II/III trial
which will assess the safety and tolerability of nirsevimab
compared to Synagis (palivizumab)
among preterm infants and children with chronic lung disease (CLD)
and congenital heart disease (CHD) entering their first and second
RSV seasons.5 The
MEDLEY trial is also expected to read out earlier with first data
anticipated in the second half of 2021. MELODY, MEDLEY and
the Phase
IIb trial will form the basis of
AstraZeneca's regulatory submissions planned for
2022.
Nirsevimab has been granted breakthrough designation by three major
regulatory agencies around the world. These include Breakthrough
Therapy Designation by The China Center for Drug Evaluation under
the National Medical Products
Administration; Breakthrough
Therapy Designation from the US Food and Drug
Administration; and access granted to the European Medicines
Agency PRIority
MEdicines (PRIME) scheme.
RSV
RSV is a common, contagious virus that infects the respiratory
tract causing millions of hospitalisations globally, and is the
most common cause of bronchiolitis and pneumonia in children
younger than one year in the US.2-4 Globally,
in 2015, there were approximately 30 million cases of acute lower
respiratory infections leading to more than three million
hospitalisations, and it was estimated that there were 60,000
in-hospital deaths of children younger than five
years.4,6 Most
hospitalisations for RSV occur in otherwise healthy infants born at
term.7-11 Medically-attended
LRTIs are associated with increased costs to the healthcare
system.12
MELODY
MELODY is a randomised, placebo-controlled Phase III trial
conducted across at least 21 countries designed to determine the
incidence of medically attended LRTI due to RSV confirmed by
reverse transcriptase polymerase chain reaction (RT-PCR) testing
through 150 days after dosing, versus placebo, in healthy infants
entering their first RSV season. Healthy late preterm and term
infants born at 35 weeks 0 days or greater gestational age were
randomised (2:1) to receive a single 50mg (in infants weighing
<5kg) or 100mg (in infants weighing >5kg) intramuscular
injection of nirsevimab or placebo. Between July 2019 and February
2021 approximately 1,500 infants were dosed with either nirsevimab
or placebo at the RSV season start.1 An
additional 1,500 infants will be enrolled in the Northern and
Southern Hemispheres to complete the safety
evaluation.
Nirsevimab
Nirsevimab is a long-acting antibody being developed as a passive
immunisation for the prevention of LRTI caused by RSV. It is being
developed for use in a broader infant population than the current
standard of care, Synagis, including for use in all infants
experiencing their first RSV season and for infants with CHD or CLD
entering their first and second RSV season.13-15 Due
to its extended half-life technology nirsevimab may only require
one dose during a typical five-month RSV season.14 The
current anti-RSV antibody,
AstraZenecaÕs Synagis, is limited to high-risk infants and provides
one-month protection, requiring five injections to cover an RSV
season.15
Nirsevimab is a passive immunisation, designed to provide RSV
protection to all infants, whereby an antibody is given directly to
an infant to help prevent RSV, unlike active immunisation,
where a person's immune system is activated to prevent or fight
infection through a vaccine.16 Passive
immunisation could offer immediate protection unlike active
immunisation, which can take weeks to develop
protection.16
In March 2017, AstraZeneca and Sanofi announced
an agreement to
develop and commercialise nirsevimab. Under the terms of the
agreement, AstraZeneca leads all development activity through
initial approvals and retains manufacturing activities and Sanofi
will lead commercialisation activities and record revenues. Under
the terms of the global agreement, Sanofi made an upfront payment
of €120m, has paid a development milestone
of €30m and will pay up to a further €465m
upon achievement of certain development and sales-related
milestones. The two companies share all costs and profits. Revenue
from the agreement is reported as Collaboration Revenue in the
Company's financial statements.
Related, in November 2018, AstraZeneca divested US commercial
rights for Synagis to
Swedish Orphan Biovitrum AB (publ) (Sobi) in addition to the right
to participate in payments that may be received by AstraZeneca from
the US profits or losses for nirsevimab. Under
the agreement,
AstraZeneca received upfront consideration of $1.5bn, consisting of
$1.0bn in cash and $500m in ordinary shares of Sobi upon
completion, and will have received a total of $60m in
non-contingent payments for nirsevimab during 2019-2021.
AstraZeneca will also receive up to $470m in sales-related payments
for Synagis,
a $175m milestone following the submission of the Biologics License
Application for nirsevimab and potential net payments of
approximately $110m on achievement of other nirsevimab profit and
development-related milestones.
AstraZeneca in Respiratory & Immunology
Respiratory & Immunology is one of AstraZeneca's three therapy
areas and is a key growth driver for the Company.
AstraZeneca is an established leader in respiratory care with a
50-year heritage. The Company aims to transform the treatment of
asthma and COPD by focusing on earlier biology-led treatment,
eliminating preventable asthma attacks, and removing COPD as a
top-three leading cause of death. The Company's early respiratory
research is focused on emerging science involving immune
mechanisms, lung damage and abnormal cell-repair processes in
disease and neuronal dysfunction.
With common pathways and underlying disease drivers across
respiratory and immunology, AstraZeneca is following the science
from chronic lung diseases to immunology-driven disease areas. The
Company's growing presence in immunology is focused on five mid- to
late-stage franchises with multi-disease potential, in areas
including rheumatology (including systemic lupus erythematosus),
dermatology, gastroenterology, and systemic eosinophilic-driven
diseases. AstraZeneca's ambition in Respiratory & Immunology is
to achieve disease modification and durable remission for millions
of patients worldwide.
AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led
biopharmaceutical company that focuses on the discovery,
development and commercialisation of prescription medicines,
primarily for the treatment of diseases in three therapy areas -
Oncology, 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
click here.
For Media contacts, click here.
References
1. Clinicaltrials.gov. A Study to Evaluate the Safety and Efficacy
of MEDI8897 for the Prevention of Medically Attended RSV LRTI in
Healthy Late Preterm and Term Infants (MELODY).
https://clinicaltrials.gov/ct2/show/NCT03979313. Accessed April
2021.
2. Piedimonte G, Perez MK. Respiratory syncytial virus infection
and bronchiolitis. Pediatr
Rev. 2014;35:519-53.
3. Oymar K, et al. Acute bronchiolitis in infants, a
review. Scand J Trauma Resusc Emerg
Med. 2014;22:23.
4. Shi T, et al. Global, regional, and national disease burden
estimates of acute lower respiratory infections due to respiratory
syncytial virus in young children in 2015: a systematic review and
modelling study. Lancet 2017;390:946Ð58.
5. Clinicaltrials.gov. A Study to Evaluate the Safety of MEDI8897
for the Prevention of Medically Attended Respiratory Syncytial
Virus (RSV) Lower Respiratory Track Infection (LRTI) in High-risk
Children. https://clinicaltrials.gov/ct2/show/NCT03959488. Accessed
April 2021.
6. Oxford Vaccines Group. What is RSV?
https://vk.ovg.ox.ac.uk/vk/rsv. Accessed April 2021.
7. Hall CB, et al. Respiratory syncytial virus-associated
hospitalizations among children less than 24 months of
age. Pediatrics. 2013;132:e341-e348.
8. Rha B, et al. Respiratory Syncytial Virus-Associated
Hospitalizations Among Young Children:
2015-2016. Pediatrics. 2020;146:e20193611.
9. Arriola CS, et al. Estimated Burden of Community-Onset
Respiratory Syncytial Virus-Associated Hospitalizations Among
Children Aged <2 Years in the United States,
2014-15. J Pediatric Infect Dis
Soc. 2020;9:587-595
10. Krilov LR, et al. Impact of the 2014 American Academy of
Pediatrics Immunoprophylaxis Policy on the Rate, Severity, and Cost
of Respiratory Syncytial Virus Hospitalizations among Preterm
Infants. Am J
Perinatol. 2020;37:174-183.
11. Scheltema NM, et al. Global respiratory syncytial
virus-associated mortality in young children (RSV GOLD): a
retrospective case series. Lancet Glob
Health. 2017;5:e984-9.
12. Zhang S, et al. Cost of Respiratory Syncytial Virus-Associated
Acute Lower Respiratory Infection Management in Young Children at
the Regional and Global Level: A Systematic Review and
Meta-Analysis. J Infect
Dis. 2020;222(Suppl
7):S680-687.
13. Villafana T, et al. Passive and active immunization against
respiratory syncytial virus for the young and
old. Expert Rev
Vaccines. 2017;16:1-39.
14. Zhu Q, et al. A highly potent extended half-life antibody
as a potential RSV vaccine surrogate for all
infants. Sci Transl
Med. 2017;9:pii:
eaaj1928
15. Synagis (palivizumab) injection prescribing
information. Available at: https://www.synagis.com/synagis.pdf
Accessed April 2021.
16. Centers for Disease Control and Prevention. Vaccines &
Immunizations. August 18, 2017.
https://www.cdc.gov/vaccines/vac-gen/immunity-types.htm. Accessed
April 2021.
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:
26 April
2021
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
|