TIDMAZN
RNS Number : 2942F
AstraZeneca PLC
04 November 2022
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,(1,4-11) and
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 EUR4.82 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, Nirsevimab Placebo Efficacy P value
n (%) (N = 969) (N = 484) (95% CI)
----------------------------------- ----------- ----------- ------------ --------
Medically attended RSV 70.1 (52.3, <0.001
LRTI 81.2)
Observed events 25 (2.6) 46 (9.5)
Participants requiring 24 (2.5) 11 (2.3)
imputation of data(*)
----------------------------------- ----------- ----------- ------------ --------
Hospitalisation for RSV 78.4 (51.9, <0.001
LRTI 90.3)
Observed events 8 (0.8) 20 (4.1)
Participants requiring 24 (2.5) 11 (2.3)
imputation of data(*)
----------------------------------- ----------- ----------- ------------ --------
(*) 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, Nirsevimab Placebo Efficacy P value
n (%) (N = 994) (N = 496) (95% CI)
------------------------------------ ----------- ----------- ------------ --------
Medically attended RSV 74.5 (49.6, <0.001
LRTI 87.1)
Observed events 12 (1.2) 25 (5.0)
Participants requiring 15 (1.5) 6 (1.2)
imputation of data(*)
------------------------------------ ----------- ----------- ------------ --------
Hospitalisation for RSV 62.1 (-8.6,
LRTI 86.8) 0.07
Observed events 6 (0.6) 8 (1.6)
Participants requiring
imputation of data(*) 15 (1.5) 6 (1.2)
------------------------------------ ----------- ----------- ------------ --------
(*) 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, Nirsevimab Placebo Efficacy (Relative P value
n (%)
(N = 1564) (N = 786) Risk
Reduction)
(95% CI)
---------------------------- ------------ ----------- ------------------ --------
Medically attended RSV 79.5 (65.9, <0.0001
LRTI 87.7)
Participants with observed 19 (1.2) 51 (6.5)
events n (%)
Participants requiring 25 (1.6) 10 (1.3)
imputation of data(*) n
(%)
---------------------------- ------------ ----------- ------------------ --------
Hospitalisation for RSV 77.3 (50.3, <0.001
LRTI 89.7)
Participants with observed 9 (0.6) 21 (2.7)
events n (%)
Participants requiring 25 (1.6) 10 (1.3)
imputation of data(*) n
(%)
---------------------------- ------------ ----------- ------------------ --------
(*) 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 EUR120m, has paid a development
milestone of EUR30m and will pay up to a further EUR465m 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
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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.
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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.
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LRTI in Healthy Preterm Infants. (MEDI8897 Ph2b).
https://www.clinicaltrials.gov/ct2/show/NCT02878330 . Accessed September 2022.
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10.1056/NEJMoa1913556.
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ESPID 2022 Congress; 2022 May 9-13. Hybrid Congress.
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for Medicinal Products for Human Use Opinion Available at:
https://www.ema.europa.eu/en/medicines/human/summaries-opinion/beyfortus.
Accessed September 2022.
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[Internet]. Available from:
https://www.medicines.org.uk/emc/product/6963/smpc Accessed
September 2022.
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https://www.cdc.gov/vaccines/vac-gen/immunity-types.htm . Accessed
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Adrian Kemp
Company Secretary
AstraZeneca PLC
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