REG - AstraZeneca PLC - Beyfortus (nirsevimab) approved in EU

AstraZenecaAnnouncement

04/11/2022 07:00

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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 €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
(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). 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)
(https://www.nejm.org/doi/full/10.1056/NEJMc2112186) 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
(https://www.nejm.org/doi/full/10.1056/nejmoa1913556) in July 2020.

 

Medically Attended LRTI and Hospitalisation for RSV LRTI Through 150 Days
Postdose (ITT population)

 Endpoints and analyses, n (%)                  Nirsevimab  Placebo     Efficacy           P value

(N = 969)
(N = 484)

                                                                        (95% CI)
 Medically attended RSV LRTI                                            70.1 (52.3, 81.2)  <0.001
 Observed events                                25 (2.6)    46 (9.5)

 Participants requiring imputation of data(*)   24 (2.5)    11 (2.3)

 Hospitalisation for RSV LRTI                                           78.4 (51.9, 90.3)  <0.001

 Observed events                                8 (0.8)     20 (4.1)

 Participants requiring imputation of data(*)   24 (2.5)    11 (2.3)

(*)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.

 

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 (https://www.nejm.org/doi/full/10.1056/NEJMoa2110275) in
March 2022.

 

Medically Attended LRTI and Hospitalisation for RSV LRTI Through 150 Days
Postdose (ITT population)

 Endpoints and analyses, n (%)                  Nirsevimab  Placebo     Efficacy           P value

(N = 994)
(N = 496)

                                                                        (95% CI)
 Medically attended RSV LRTI                                            74.5 (49.6, 87.1)  <0.001
 Observed events                                12 (1.2)    25 (5.0)

 Participants requiring imputation of data(*)   15 (1.5)    6 (1.2)

 Hospitalisation for RSV LRTI                                           62.1 (-8.6, 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, n (%)                        Nirsevimab   Placebo     Efficacy (Relative  P value

(N = 1564)
(N = 786)

                                                                               Risk

                                                                               Reduction)

(95% CI)
 Medically attended RSV LRTI                                                   79.5 (65.9, 87.7)    <0.0001
 Participants with observed events n (%)              19 (1.2)     51 (6.5)

 Participants requiring imputation of data(*) n (%)

                                                      25 (1.6)     10 (1.3)
 Hospitalisation for RSV LRTI                                                  77.3 (50.3, 89.7)    <0.001
 Participants with observed events n (%)              9 (0.6)      21 (2.7)

 Participants requiring imputation of data(*) n (%)

                                                      25 (1.6)     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
(https://nam12.safelinks.protection.outlook.com/?url=https%3A%2F%2Fwww.astrazeneca.com%2Fmedia-centre%2Fpress-releases%2F2017%2Fmedimmune-and-sanofi-pasteur-form-alliance-to-develop-and-commercialise-potential-next-generation-respiratory-syncytial-virus-antibody-medi8897-030317.html&data=04%7C01%7Celeanor.read%40edelman.com%7Ca3c20243fe85477f1b3808d90636596f%7Cb824bfb3918e43c2bb1cdcc1ba40a82b%7C0%7C0%7C637547652770793519%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C1000&sdata=ZcJELgHfl6iZMI7f3qCFUOW4miRNoLSrIxbCrVRDGzk%3D&reserved=0)
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
(https://www.astrazeneca.com/media-centre/press-releases/2018/astrazeneca-to-divest-us-synagis-rights-to-sobi131120180.html)
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 (https://www.astrazeneca.com/) and follow the
Company on Twitter @AstraZeneca (https://twitter.com/AstraZeneca) .

 

Contacts

For details on how to contact the Investor Relations Team, please click here
(https://www.astrazeneca.com/investor-relations.html#Contacts) . For Media
contacts, click here (https://www.astrazeneca.com/media-centre/contacts.html)
.

 

References

1.   European Commission.
https://ec.europa.eu/transparency/documentsregister/detail?ref=C(2022)7992&lang=en
(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
(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
(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
(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
(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
(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

 

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