REG - AstraZeneca PLC - Beyfortus approved in US for infant RSV prevention

AstraZenecaAnnouncement

17/07/2023 18:15

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RNS Number : 2865G  AstraZeneca PLC  17 July 2023

 

 

17 July 2023

 

Beyfortus approved in the US for the prevention of RSV

lower respiratory tract disease in infants

 

First preventive option specifically designed to protect

the broad infant population through its first RSV season

 

Across all clinical endpoints, a single dose of Beyfortus delivered consistent
and sustained efficacy against RSV disease vs placebo

 

AstraZeneca and Sanofi's Beyfortus (nirsevimab) has been approved in the US
for the prevention of respiratory syncytial virus (RSV) lower respiratory
tract disease (LRTD) in newborns and infants born during or entering their
first RSV season, and for children up to 24 months of age who remain
vulnerable to severe RSV disease through their second RSV season. Beyfortus
will be available in the US ahead of the upcoming 2023-2024 RSV season.

 

The approval by the Food and Drug Administration (FDA) follows the unanimous
(https://www.astrazeneca.com/media-centre/press-releases/2023/nirsevimab-recommended-for-infant-rsv-protection.html)
vote by the Antimicrobial Drugs Advisory Committee (AMDAC) on the favourable
benefit-risk profile of Beyfortus, and was based on the extensive clinical
development programme for Beyfortusspanning three pivotal late-stage clinical
trials. Across all clinical endpoints, a single dose of Beyfortus demonstrated
consistent efficacy against RSV LRTD extending through five months, the
duration of a typical RSV season.(1-4)

 

Beyfortus is the first preventive option approved to protect a broad infant
population, including those born healthy at term, or preterm, or with specific
health conditions that make them vulnerable to severe RSV disease. The single
dose can be flexibly administered at the beginning of the RSV season or at
birth for those born during the RSV season.

 

Iskra Reic, Executive Vice President, Vaccines and Immune Therapies,
AstraZeneca, said: "Beyfortus represents an opportunity for a paradigm-shift
in preventing serious respiratory disease due to RSV across a broad infant
population in the US. The science that Beyfortus is built on demonstrates
AstraZeneca's continued leadership in addressing the needs of the most
vulnerable populations and reducing the burden on healthcare systems."

 

Thomas Triomphe, Executive Vice President, Vaccines, Sanofi, said: "Today's
approval marks an unprecedented moment for protecting infant health in the
U.S., following an RSV season that took a record toll on infants, their
families, and the U.S. healthcare system. Beyfortus is the only monoclonal
antibody approved for passive immunisation  to provide safe and effective
protection for all infants during their first RSV season. I am proud that, by
prioritising this potential game-changer, we are now about to bring Beyfortus
to American families."

 

RSV is the leading cause of hospitalisation for infants under the age of one
in the US, averaging 16 times higher than the annual rate for influenza.(5,6)
Each year, an estimated 590,000 RSV disease cases in infants under one require
medical care, including physician office, urgent care, emergency room visits
and hospitalisations.(7)

 

Beyfortus was generally well tolerated with a favourable safety profile that
was consistent across all clinical trials. The overall rates of adverse events
were comparable between Beyfortusand placebo and the majority of adverse
events were mild or moderate in severity. The most common adverse events were
rash and injection site reactions.(1-4)

 

Beyfortus was approved in the European Union in October 2022 for the
prevention of RSV LRTD in newborns and infants during their first RSV season.
Regulatory applications are also currently under review in China, Japan and
several other countries.

 

Notes

 

RSV

RSV is a very contagious virus that can lead to serious respiratory illness
for infants, according to the Centers for Disease Control and Prevention
(CDC). RSV symptoms can include runny nose, coughing, sneezing, fever,
decrease in appetite, and wheezing.(8) Two out of three infants are infected
with RSV during their first year of life and almost all infants are infected
by their second birthday.(8,9) In the US, RSV is the leading cause of
hospitalisation in infants under 12 months, averaging 16 times higher than the
annual rate for influenza.(5,6) Approximately 75% of infants hospitalised for
RSV were born at term with no underlying conditions in a study conducted from
2014-2015.(10) Each year in the US, an estimated 590,000 RSV disease cases in
infants under one require medical care, including physician office, urgent
care, emergency room visits and hospitalisations.(7)

 

Beyfortus

Beyfortus (nirsevimab) is a single dose long-acting antibody, developed and
commercialised in partnership by AstraZeneca and Sanofi using AstraZeneca's
YTE technology. It is designed to protect infants born during or entering
their first RSV season and for children up to 24 months of age who remain
vulnerable to severe RSV disease through their second RSV season.
Beyfortus,provided directly to newborns and infants as a single dose, offers
rapid protection via an antibody to help prevent LRTD caused by RSV, without
requiring activation of the immune system. Beyfortus administration can be
timed to the start of the RSV season.(11)

 

Beyfortushas been granted regulatory designations to facilitate expedited
development by several major regulatory agencies around the world. These
include Breakthrough Therapy Designation and Priority Review Designation by
the China Center for Drug Evaluation under the National Medical Products
Administration; Breakthrough Therapy
(https://www.astrazeneca.com/media-centre/press-releases/2019/us-fda-grants-breakthrough-therapy-designation-for-potential-next-generation-rsv-medicine-medi8897.html)
Designation
(https://www.astrazeneca.com/media-centre/press-releases/2019/us-fda-grants-breakthrough-therapy-designation-for-potential-next-generation-rsv-medicine-medi8897.html)
from the US Food and Drug Administration; access granted to the European
Medicines Agency (EMA PRIority MEdicines
(https://www.astrazeneca.com/media-centre/press-releases/2019/ema-grants-prime-eligibility-for-potential-next-generation-rsv-medicine-medi8897-05022019.html)
(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).

 
Pivotal clinical trials

The Phase IIb (Trial 03) study was a randomised, placebo-controlled trial
designed to measure the efficacy of Beyfortus against medically attended (MA)
Lower Respiratory Tract Infection (LRTI) through 150 days post-dose. Healthy
preterm infants of 29 to less than 35 weeks' gestational age were randomised
(2:1) to receive a single 50mg intramuscular injection of Beyfortusor placebo
regardless of weight.(3,12)

 

The Beyfortusdosing regimen was determined based on further exploration of the
Phase IIb data and was used in subsequent trials as a single 50 mg dose for
those who weigh less than 5 kg, or a single 100 mg dose for those who weigh 5
kg or greater.(3,12)

 

The MELODY Phase III study (Trial 04) was a randomised, double-blind, placebo-
controlled trial conducted across 21 countries designed to determine efficacy
of Beyfortus against medically attended LRTI due to through 150 days after
dosing, versus placebo, in healthy term and late preterm infants (35 weeks
gestational age or greater) entering their first RSV season.(1,2,12)

 

MEDLEY (Trial 05) was a Phase II/III, randomised, double-blind,
Synagis-controlled trial with the primary objective of assessing safety and
tolerability for Beyfortusin preterm infants of less than 35 weeks gestational
age and infants with congenital heart disease (CHD) and/or chronic lung
disease of prematurity (CLD) eligible to receive Synagis.(4,12) Between July
2019 and May 2021 a total of 925 infants entering their first RSV season were
randomised to receive Beyfortus or Synagis. Safety was assessed by monitoring
the occurrence of adverse events through 360 days post-dose. 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 were published in the New England Journal of Medicine (NEJM)
(https://www.nejm.org/doi/full/10.1056/NEJMc2112186) in March 2022.(4,12)

 

The safety profile of Beyfortus was similar to Synagis in the MEDLEY Phase
II/III trial and consistent with the safety profile in healthy term and
preterm infants studied in the MELODY and Phase IIb trials. While uncommon,
the most reported adverse reactions were: rash 14 days post-dose, (the
majority of which were mild to moderate; non-serious injection site reactions
within 7 days post-dose.(1,2,4,12)

 

The results of MELODY, MEDLEY Phase II/III and the Phase IIb trials
demonstrate that a single dose of nirsevimab helps protect infants during
their first RSV season against RSV disease. This broad infant population
includes healthy term, late preterm and preterm infants, as well as infants
with specific health conditions that make them vulnerable to severe RSV
disease.(1-4,12)

 

These trials formed the basis of regulatory submissions which began in 2022.

 

Results from the MELODY Phase III trial (Trial 04)

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 74.9%

(95% CI 50.6, 87.3; P<0.001) compared to placebo.(1,2) Observed events were
1.2% in treatment arm vs 5% in placebo arm. The efficacy of Beyfortus against
the secondary endpoint of hospitalisation was 60.2% (95% CI: -14.6, 86.2).
Observed events were 0.6% in treatment arm vs 1.6% in placebo arm. Between
July 2019 and March 2020, 1,490 infants were randomised to receive either
nirsevimab or placebo at the RSV season start Initial data from the MELODY
Primary Cohort were published in NEJM
(https://protect-de.mimecast.com/s/mojGCPjn9GHNKMG0ESzLmtG?domain=urldefense.com)
in March 2022 (12)

 

Results from the Phase IIb trial (Trial 03)

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. Observed events were 2.6% in treatment arm vs 9.5% in placebo arm.
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.
Data were published in NEJM
(https://www.nejm.org/doi/full/10.1056/nejmoa1913556) in July 2020.(3,12)

 

In a prespecified secondary endpoint, Beyfortusreduced medically attended RSV
LRTI with hospitalisation by 78.4% (95% CI 51.9, 90.3) versus placebo.
Observed events were 0.8% in treatment arm vs 4.1% in placebo arm.(3,12) A
post-hoc analysis of the Phase IIb study that applied the recommended 50 mg
dose in a subgroup of infants weighing less than 5 kg showed the efficacy of
Beyfortus against medically attended RSV LRTI and medically attended RSV LRTI
with hospitalisation was 86.2% (95% CI 68.0, 94.0) and

86.5% (95% CI 53.5, 96.1), respectively.(12)

 

Sanofi Alliance

In March 2017, AstraZeneca and Sanofi announced
(https://www.astrazeneca.com/media-centre/press-releases/2017/medimmune-and-sanofi-pasteur-form-alliance-to-develop-and-commercialise-potential-next-generation-respiratory-syncytial-virus-antibody-medi8897-030317.html)
an agreement to develop and commercialise nirsevimab. Under the terms of the
agreement, AstraZeneca leads development and manufacturing activities, and
Sanofi leads commercialisation activities and records revenue. The two
companies share costs and profits in all territories except the US.
AstraZeneca's revenue from the agreement is reported as Alliance Revenue and
Collaboration Revenue in the Company's financial statements. Following a
revision
(https://www.astrazeneca.com/media-centre/press-releases/2023/update-to-arrangements-with-sobi-and-sanofi.html)
to the profit-sharing arrangement relating to the development and
commercialisation of nirsevimab in the US between AstraZeneca, Sanofi and
Sobi, Sobi has entered into a direct relationship with Sanofi, replacing the
previous participation agreement with AstraZeneca entered into in November
(https://www.astrazeneca.com/media-centre/press-releases/2018/astrazeneca-to-divest-us-synagis-rights-to-sobi131120180.html)
2018
(https://www.astrazeneca.com/media-centre/press-releases/2018/astrazeneca-to-divest-us-synagis-rights-to-sobi131120180.html)
.

 

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 (http://www.astrazeneca.com/) and follow the
Company on Twitter @AstraZeneca (https://twitter.com/AstraZeneca) .

 

Contacts
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.
References

1.    Muller WJ, et al. Nirsevimab for Prevention of RSV in Term and
Late-Preterm Infants. N Engl J Med. April 5, 2023. DOI: 10.1056/NEJMc2214773

2.    Hammitt LL, 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.

3.    Griffin P, MD et al. Single-Dose Nirsevimab for Prevention of RSV in
Preterm Infants. N Engl J Med. 2020;383: 415-425. DOI: 10.1056/NEJMoa1913556.

4.    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).

5.    Leader S, Kohlhase K. Recent trends in severe respiratory syncytial
virus (RSV) among US infants, 1997 to 2000. J Pediatr. 2003;143(5
Suppl):S127-S132. Doi:10.1067/s0022-

3476(03)00510-9.

6.    Zhou H, et al. Hospitalizations associated with influenza and
respiratory syncytial virus in the United States, 1993-2008. Clin Infect Dis.
2012 ;54 :1427-1436.

7.    Rainisch G, et al. Estimating the impact of multiple immunization
products on medically- attended respiratory syncytial virus (RSV) infections
in infants. Vaccine. 2020;38(2):251-257.

8.    Centers for Disease Control and Prevention. RSV in Infants and Young
Children. October 28, 2022.
https://www.cdc.gov/rsv/high-risk/infants-young-children.html.
(http://www.cdc.gov/rsv/high-risk/infants-young-children.html) Accessed July
2023.

9.    Walsh, EE. Respiratory Syncytial Virus infection: an illness for all
ages. Clin Chest Med. 2017; 38(1):29-36.

10.  Esposito S, et al. RSV Prevention in All Infants: Which Is the Most
Preferable Strategy? Front Immunol. 2022; 13: 880368. doi:
10.3389/fimmu.2022.880368.

11.  Centers for Disease Control and Prevention. Vaccines &
Immunizations. August 18, 2017. https://w
(http://www.cdc.gov/vaccines/vac-gen/immunity-types.htm)
ww.cdc.gov/vaccines/vac-gen/immunity-types.htm.
(http://www.cdc.gov/vaccines/vac-gen/immunity-types.htm) Accessed July 2023.

12.  US FDA. Beyfortus (nirsevimab-alip) Prescribing Information.

 

 

Adrian Kemp Company Secretary AstraZeneca PLC

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