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 November 2022
Commission
File Number: 001-11960
AstraZeneca PLC
1
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Cambridge
Biomedical Campus
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United
Kingdom
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Beyfortus (nirsevimab) approved in EU
4 November 2022 07:00 GMT
Beyfortus approved
in the EU for the prevention of RSV lower
respiratory tract disease in infants
First and only single-dose RSV preventative option approved for
broad
newborn and infant population
European Commission grants first approval worldwide
following
positive CHMP opinion in September
AstraZeneca and Sanofi's Beyfortus (nirsevimab) has been approved in the
European Union (EU) for the prevention of respiratory syncytial
virus (RSV) lower respiratory tract disease in newborns and infants
during their first RSV season.1 Beyfortus is
the first and only single-dose RSV passive immunisation for the
broad infant population, including those born healthy, at term or
preterm, or with specific health conditions.
RSV is a common and highly contagious seasonal virus, infecting
nearly all children by the age of two.2,3
The European Commission is the first regulatory body to grant
approval to Beyfortus.1 The
approval was based on results from the Beyfortus clinical development programme, including
the MELODY Phase III, MEDLEY Phase II/III and Phase IIb
trials,1,4-11and
follows the recommendation by The Committee for Medicinal Products
for Human Use (CHMP) of the European Medicines Agency in September
2022.12
In the pivotal MELODY efficacy trial, Beyfortus met its primary endpoint of reducing the
incidence of medically attended lower respiratory tract infections
(LRTI) caused by RSV by 74.5% (95% CI 49.6, 87.1; p<0.001) vs.
placebo through day 151 (a typical RSV season) with a single
dose.1,4-9 Beyfortus also
demonstrated a comparable safety and tolerability profile
to Synagis (palivizumab) in the MEDLEY Phase II/III
trial, with occurrence of treatment emergent adverse events (TEAEs)
or treatment emergent serious adverse events (TESAEs) similar
between groups.1,10-13
Silke Mader, Chairwoman of the Executive Board and Co-founder of
the European Foundation for the Care of Newborn Infants (EFCNI),
said: "Respiratory syncytial virus represents a health threat among
infants, and each year we see the impact it can have on families,
healthcare providers and the healthcare system. At EFCNI, we are
excited about the opportunity to expand prevention efforts to all
infants, as we believe this can help ease the current emotional,
physical and financial burdens of RSV."
Iskra Reic, Executive Vice President, Vaccines and Immune
Therapies, AstraZeneca, said: "Beyfortus is the first single-dose preventative option
against respiratory syncytial virus to gain approval in Europe and
is also the first and only preventative option approved for a broad
infant population. Today's marketing authorisation
of Beyfortus marks a significant achievement for the
scientific community and addresses a persistent, global unmet need
in RSV prevention."
Thomas Triomphe, Executive Vice President, Vaccines, Sanofi, said:
"Today is a landmark day for RSV prevention, as decades of research
and development come together in the world's first approval of a
broadly protective option against respiratory syncytial virus
disease. Once launched, Beyfortus will
offer parents the ability to help protect their babies during their
first RSV season."
RSV is the most common cause of LRTI, including bronchiolitis and
pneumonia in infants.14 It
is also a leading cause of hospitalisation in all
infants.15-18 Globally,
in 2019, there were approximately 33 million cases of acute lower
respiratory infections leading to more than three million
hospitalisations, and it was estimated that there were 26,300
in-hospital deaths of children younger than five
years.19 RSV-related
direct medical costs, globally - including hospital, outpatient and
follow-up care - were estimated at €4.82 billion in
2017.21
Notes
Beyfortus
Beyfortus (nirsevimab),
a long-acting antibody designed for all infants for protection
against RSV disease from birth through their first RSV season with
a single dose, is being developed jointly by AstraZeneca and Sanofi
using AstraZeneca's YTE technology.
Beyfortus has
been developed to offer newborns and infants direct RSV protection
via an antibody to help prevent LRTI caused by
RSV. Monoclonal
antibodies do not require the activation of the immune system to
help offer timely, rapid and direct protection against
disease.20
Beyfortus has
been granted marketing authorisation in the European Union for the
prevention of RSV LRTI disease in newborns and infants from birth
during their first RSV season. The recommended dose
of Beyfortus is
a single intramuscular injection of 50 mg for infants with body
weight <5 kg and a single intramuscular injection of 100 mg for
infants with body weight ≥5 kg.12
Beyfortus has
also been granted regulatory designations to facilitate expedited
development by several 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; access granted to the European
Medicines Agency (EMA PRIority
Medicines (PRIME)
scheme; and named "a medicine for prioritized development" under
the Project for Drug Selection to Promote New Drug Development in
Pediatrics by the Japan Agency for Medical Research and Development
(AMED). The safety and efficacy of Beyfortus was
evaluated under an accelerated assessment procedure by the
EMA.
Pivotal clinical trials
The Phase IIb study was a randomised, placebo-controlled trial
designed to measure the efficacy of Beyfortus (nirsevimab)
against medically attended LRTI through 150 days postdose. Healthy
preterm infants of 29-35 weeks' gestation were randomised (2:1) to
receive a single 50mg intramuscular injection
of Beyfortus or
placebo.1,4,5
The dosing regimen was recommended based
on further exploration of the Phase IIb data. The subsequent Phase
III study, MELODY applied the recommended dosing
regimen.1,3,6
The MELODY Phase III study was a randomised, placebo-controlled
trial conducted across 21 countries designed to determine efficacy
of Beyfortus against medically attended LRTI due to RSV
confirmed by reverse transcriptase polymerase chain reaction
testing through 150 days after dosing, versus placebo, in healthy
late preterm and term infants (35 weeks gestational age or greater)
entering their first RSV season.1-3
MEDLEY was a Phase II/III, randomised,
double-blind, Synagis-controlled
trial with the primary objective of assessing safety and
tolerability for Beyfortus in
preterm infants and infants with congenital heart disease (CHD)
and/or chronic lung disease of prematurity (CLD) eligible to
receive Synagis.1,8,9 Between
July 2019 and May 2021 approximately 918 infants entering their
first RSV season were randomised to receive a single 50mg (in
infants weighing <5kg) or 100mg (in infants weighing ≥5kg)
intramuscular injection of Beyfortus or Synagis.
Safety was assessed by monitoring the occurrence of TEAEs and
TESAEs through 360 days post-dose.1,8,9 Serum
levels of Beyfortus following
dosing (on day 151) in this trial were comparable with those
observed in the MELODY Phase III trial, indicating similar
protection in this population to that in the healthy term and late
preterm infants is likely. Data was published in
the New
England Journal of Medicine (NEJM) in
March 2022.
The results of MELODY, MEDLEY Phase II/III and the Phase IIb trials
demonstrate that Beyfortus helps protect infants during their first RSV
season against RSV disease with a single dose.1-9 This
all-infant population includes preterm, healthy late preterm and
term infants, as well as infants with specific
conditions.
These trials form the basis of regulatory submissions which began
in 2022.
Results from the Phase IIb trial
The primary endpoint of the
Phase IIb study was
met, reducing the incidence of medically attended LRTI, caused by
RSV by 70.1% (95% CI: 52.3, 81.2) compared to
placebo. Between
November 2016 and December 2017, 1,453 infants were randomised
(Beyfortus,
n=969; placebo, n=484) at the RSV season start. Research was
conducted by AstraZeneca in both hemispheres, at 164 sites in 23
countries.1,4,5 Data
was published in NEJM in
July 2020.
Medically Attended LRTI and Hospitalisation for RSV LRTI Through
150 Days Postdose (ITT population)
|
Endpoints
and analyses, n (%)
|
Nirsevimab(N
= 969)
|
Placebo(N
= 484)
|
Efficacy
(95%
CI)
|
P
value
|
|
Medically
attended RSV LRTI
|
|
|
70.1
(52.3, 81.2)
|
<0.001
|
|
Observed
events
Participants
requiring imputation of data*
|
25
(2.6)
24
(2.5)
|
46
(9.5)
11
(2.3)
|
|
|
|
Hospitalisation
for RSV LRTI
Observed
events
Participants
requiring imputation of data*
|
8
(0.8)
24
(2.5)
|
20
(4.1)
11
(2.3)
|
78.4
(51.9, 90.3)
|
<0.001
|
*Data were imputed for
participants who had no events and were not followed through 150
days postdose. Analyses were conducted using Poisson regression
with robust variance. CI, confidence interval; ITT,
intent-to-treat; LRTI, lower respiratory tract infection; RRR,
relative risk reduction; RSV, respiratory syncytial
virus.
Results from the MELODY Phase
III trial
The primary endpoint of the MELODY Phase
III trial was
met, reducing the incidence of medically attended LRTI, such as
bronchiolitis or pneumonia, caused by RSV by 74.5% (95% CI 49.6,
87.1; P<0.001) compared to placebo. Infants
were randomised (2:1) to receive a single 50mg (in infants weighing
<5kg) or 100mg (in infants weighing ≥5kg) intramuscular
injection of Beyfortus or
placebo. Between July 2019 and March 2020, 1,490 infants were
randomised to either Beyfortus or
placebo at the RSV season start.1-3 Data
was published in NEJM in
March 2022.
Medically Attended LRTI and Hospitalisation for RSV LRTI Through
150 Days Postdose (ITT population)
|
Endpoints
and analyses, n (%)
|
Nirsevimab(N
= 994)
|
Placebo(N
= 496)
|
Efficacy
(95%
CI)
|
P
value
|
|
Medically
attended RSV LRTI
|
|
|
74.5
(49.6, 87.1)
|
<0.001
|
|
Observed
events
Participants
requiring imputation of data*
|
12
(1.2)
15
(1.5)
|
25
(5.0)
6
(1.2)
|
|
|
|
Hospitalisation
for RSV LRTI
Observed
events
Participants
requiring imputation of data*
|
6
(0.6)
15
(1.5)
|
8
(1.6)
6
(1.2)
|
62.1
(-8.6, 86.8)
|
0.07
|
*Data were imputed for
participants who had no events and were not followed through 150
days postdose. Analyses were conducted using Poisson regression
with robust variance. CI, confidence interval; ITT,
intent-to-treat; LRTI, lower respiratory tract infection; RRR,
relative risk reduction; RSV, respiratory syncytial
virus.
Results from the pre-specified pooled analysis of the Phase IIb and
MELODY trials
A prespecified pooled analysis of the MELODY Phase III trial and
the recommended dose from the Phase IIb trial, in which an efficacy
(relative risk reduction versus placebo) of 79.5% (95% CI 65.9,
87.7; P<0.0001) was seen against medically attended LRTI, such
as bronchiolitis or pneumonia, caused by RSV in infants born at
term or preterm entering their first RSV season.1,8 The
pooled analysis studied healthy preterm and term infants who
received the recommended dose of Beyfortus based on weight compared to placebo through
Day 151 and showed an efficacy of 77.3% (95% CI 50.3, 89.7;
P<0.001) against RSV LRTI hospitalisations.1,4,8
Medically Attended LRTI and Hospitalisation for RSV LRTI Through
150 Days Postdose (ITT population)
|
Endpoints
and analyses, n (%)
|
Nirsevimab(N
= 1564)
|
Placebo(N
= 786)
|
Efficacy
(Relative
Risk
Reduction)(95%
CI)
|
P
value
|
|
Medically
attended RSV LRTI
|
|
|
79.5
(65.9, 87.7)
|
<0.0001
|
|
Participants with
observed events n (%)
Participants
requiring imputation of data* n
(%)
|
19
(1.2)
25
(1.6)
|
51
(6.5)
10
(1.3)
|
|
|
|
Hospitalisation
for RSV LRTI
|
|
|
77.3
(50.3, 89.7)
|
<0.001
|
|
Participants with
observed events n (%)
Participants
requiring imputation of data* n
(%)
|
9
(0.6)
25
(1.6)
|
21
(2.7)
10
(1.3)
|
|
|
*Data were imputed for
participants who had no events and were not followed through 150
days postdose. Analyses were conducted using Poisson regression
with robust variance. CI, confidence interval; ITT,
intent-to-treat; LRTI, lower respiratory tract infection; RRR,
relative risk reduction; RSV, respiratory syncytial
virus.
Sanofi Alliance
In March 2017, AstraZeneca and Sanofi announced
an agreement to
develop and commercialise nirsevimab. Under the terms of the
agreement, AstraZeneca leads all development and manufacturing
activities, and Sanofi leads commercialisation activities and
records revenue. 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 costs and profits. Revenue from
the agreement is reported as Collaboration Revenue in the Company's
financial statements.
Sobi agreement
Related, in November 2018, AstraZeneca agreed to sell US commercial
rights for Synagis (palivizumab)
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 and also received non-contingent
payments for nirsevimab during 2019-2021. AstraZeneca is also
entitled to receive certain milestone payments for nirsevimab,
including a $175m milestone following the date on which the
Biologics License Application (BLA) for nirsevimab is accepted for
filing by the FDA and a $90m milestone payment following the date
on which BLA approval in the US occurs. AstraZeneca will continue
to manufacture and supply nirsevimab globally and is entitled to an
additional royalty from Sobi if profits from nirsevimab in the US
exceed a pre-specified level.
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, Rare Diseases, 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
click here.
For Media contacts, click here.
References
1. European
Commission. https://ec.europa.eu/transparency/documentsregister/detail?ref=C(2022)7992&lang=en
Accessed
November 2022
2.
Glezen WP et al. Am J Dis Child. 1986;140(6):543-5463.
3.
Collins et al. Journal of Virology. 2008:2040-2055.
4.
Hammitt LL, MD et al. Nirsevimab for Prevention of RSV in Healthy
Late -Preterm and Term Infants. N Engl J Med. 2022;386 (9):
837-846. doi: 10.1056/NEJMoa2110275.
5.
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 September 2022.
6.
Clinicaltrials.gov. A Study to Evaluate the Safety and Efficacy of
MEDI8897 for the Prevention of Medically Attended RSV LRTI in
Healthy Preterm Infants. (MEDI8897 Ph2b). https://www.clinicaltrials.gov/ct2/show/NCT02878330 .
Accessed September 2022.
7.
Griffin P, MD et al. (2020). Single-Dose Nirsevimab for Prevention
of RSV in Preterm Infants. NEJM 2020; 383: 415-425. DOI:
10.1056/NEJMoa1913556.
8.
Simões, E, et al. Pooled efficacy of nirsevimab against RSV
lower respiratory tract infection in preterm and term infants.
ESPID 2022 Congress; 2022 May 9-13. Hybrid Congress.
9.
Wilkins, D, et al. Nirsevimab for the prevention of respiratory
syncytial virus infection: neutralizing antibody levels following a
single dose. ESPID 2022 Congress; 2022 May 9-13. Hybrid
Congress.
10.
Domachowske J, MD et al. Safety of Nirsevimab for RSV in Infants
with Heart or Lung Disease or Prematurity. N Engl J Med. 2022; 386
(9).
11. 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 (MEDLEY).
Accessed September 2022.
12.
European Medicines Agency. Beyfortus Summary of Committee for
Medicinal Products for Human Use Opinion Available at:
https://www.ema.europa.eu/en/medicines/human/summaries-opinion/beyfortus.
Accessed September 2022.
13. Synagis - Summary of
Product Characteristics (SmPC) - (eMC) [Internet]. Available
from: https://www.medicines.org.uk/emc/product/6963/smpc Accessed
September 2022.
14.
R K. Respiratory Syncytial Virus Vaccines. Plotkin SA, Orenstein
WA, Offitt PA, Edwards KM, eds Plotkin's Vaccines 7th ed
Philadelphia. 2018;7th ed. Philadelphia:943-9.
15.
Leader S, Kohlhase K. Respiratory syncytial virus-coded pediatric
hospitalizations, 1997 to 1999. The Pediatric infectious disease
journal. 2002;21(7):629-32.
16.
McLaurin KK, Farr AM, Wade SW, Diakun DR, Stewart DL. Respiratory
syncytial virus hospitalization outcomes and costs of full-term and
preterm infants. Journal of Perinatology: official journal of the
California Perinatal Association. 2016;36(11):990-6.
17.
Rha B, et al. Respiratory Syncytial Virus-Associated
Hospitalizations Among Young Children: 2015-2016. Pediatrics.
2020;146:e20193611.
18.
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
19.
Li Y, et al. Global, regional, and national disease burden
estimates of acute lower respiratory infections due to respiratory
syncytial virus in children younger than 5 years in 2019: a
systematic analysis. Lancet 2022;399:92047-64.
20. Centers for Disease
Control and Prevention. Vaccines & Immunizations. August 18,
2017. https://www.cdc.gov/vaccines/vac-gen/immunity-types.htm.
Accessed September 2022.
21.
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.
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:
04 November 2022
|
|
By: /s/
Adrian Kemp
|
|
|
Name:
Adrian Kemp
|
|
|
Title:
Company Secretary
|
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