TIDMAZN
RNS Number : 2366D
AstraZeneca PLC
28 June 2021
28 June 2021 07:00 BST
Nirsevimab MEDLEY Phase II/III trial demonstrated favourable
safety
and tolerability profile in infants at high risk of RSV
Nirsevimab is being developed as a passive immunisation against
RSV for all infants
The MEDLEY Phase II/III trial evaluated the safety and
tolerability of nirsevimab compared to Synagis (palivizumab) when
given to infants at high risk of respiratory syncytial virus (RSV)
entering their first RSV season. (1)
The trial assessed the safety of nirsevimab in infants with
chronic lung disease (CLD), congenital heart disease (CHD) and/or
prematurity. Occurrence of treatment emergent adverse events
(TEAEs) or treatment emergent serious adverse events (TESAEs) were
similar between groups. (1)
Nirsevimab is a long-acting antibody, using AstraZeneca's
proprietary YTE technology, being developed by AstraZeneca and
Sanofi with the potential to provide immunity directly to all
infants and offer immediate protection against RSV through the
entire season with a single dose.
Dr Joseph Domachowske, Professor of Pediatrics and Professor of
Microbiology and Immunology at the State University of New York,
Upstate Medical Center, Syracuse, NY and MEDLEY trial primary
investigator, said: "These data for nirsevimab are important as
they show a safety and tolerability profile comparable to the only
available preventative option against lower respiratory tract
infections caused by respiratory syncytial virus for preterm
infants and those with health conditions. Given the typical
respiratory syncytial virus season lasts nearly five months, there
is a potential advantage to providing a preventative option that
could help protect all infants with one dose for the entire
season."
Mene Pangalos, Executive Vice President, BioPharmaceuticals
R&D, said: "Respiratory syncytial virus is the leading cause of
hospitalisations in infants. These results, combined with the
recent positive efficacy outcome of our MELODY Phase III trial and
our Phase IIb data, contribute to the body of evidence
demonstrating nirsevimab's potential to protect all infants against
respiratory syncytial virus with one dose. We look forward to
sharing the results with regulators."
Jean-François Toussaint, Global Head of Research and
Development, Sanofi Pasteur: "Respiratory syncytial virus is the
major remaining paediatric infectious disease with no preventative
option available to all infants. We believe nirsevimab has the
potential to become an important and innovative routine
immunisation for all infants - those born prematurely or at term,
healthy or with health conditions."
Full results from the MEDLEY trial will be presented at a
forthcoming medical meeting. The trial is ongoing to collect
additional safety data.
Nirsevimab is also being evaluated in the MELODY Phase III
trial, which met its primary endpoint of a statistically
significant reduction in the incidence of medically attended LRTI
caused by RSV, compared to placebo, in healthy late preterm and
term infants during their first RSV season. MEDLEY, MELODY and the
Phase IIb trial will form the basis of AstraZeneca's regulatory
submissions planned from the first half of 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 pathogen that causes seasonal
epidemics of lower respiratory tract infections (LRTI), including
bronchiolitis and pneumonia.(2-4) It is the leading cause of
hospitalisations in infants worldwide.(4) Currently, Synagis is the
only approved option for the prevention of serious LRTI caused by
RSV in preterm infants and infants at high risk and requires up to
five injections to cover a typical RSV season. (5) 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)
MEDLEY
MEDLEY is a Phase II/III, randomised, double-blind,
Synagis-controlled trial with the primary objective of assessing
safety and tolerability for nirsevimab in preterm infants and
infants at high risk eligible to receive Synagis. Between July 2019
and May 2021 approximately 925 infants entering their first RSV
season were dosed with either nirsevimab or Synagis. Safety is
assessed by monitoring the occurrence of TEAEs and TESAEs through
360 days post-dose. High-risk infants are defined as infants 35
weeks 0 days or lesser gestational age without CLD/CHD, or infants
with CLD of prematurity or hemodynamically significant CHD.(1)
The evaluation of the safety and tolerability of nirsevimab in
the MEDLEY trial was carried out earlier than anticipated. A
primary analysis was conducted to allow earlier assessment of
nirsevimab's safety and tolerability versus Synagis based on a
sufficient number of infants being enrolled and followed through
their first RSV season.
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.(13) 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 with all infants, in comparison to the
current standard of care, Synagis, which is limited to infants at
high risk.(5, 14,15) Due to its extended half-life technology,
nirsevimab may only require one dose during a typical five-month
RSV season. (15) The current anti-RSV antibody, AstraZeneca's
Synagis, is limited to high-risk infants and provides one-month
protection, requiring five injections to cover an RSV
season.(5)
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
the infants' own immune system is activated to prevent or fight
infection.(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 and manufacturing
activities and Sanofi will lead commercialisation activities and
record revenues. 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 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 (BLA) for
nirsevimab and potential net payments of approximately $110m on
achievement of other nirsevimab profit and development-related
milestones. Upon payment of the $175m milestone on BLA submission,
Sobi's ongoing participation will amount to AstraZeneca's full
share of profits or losses under the agreement with Sanofi for
nirsevimab in the US. 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 in Respiratory & Immunology
Respiratory & Immunology, part of BioPharmaceuticals, is one
of AstraZeneca's three disease 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 in
Oncology 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
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please click here . For Media contacts, click here .
References
1. 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 June
2021.
2. Piedimonte G, Perez MK. Pediatr Rev. 2014;35(12):519-53
3. Oymar K et al. 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: 946-58.
5. Synagis (palivizumab) injection prescribing information.
Available at: https://www.synagis.com/synagis.pdf. Accessed June
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. J Infect Dis . 2020. doi: 10.1093/infdis/jiz683
13. 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 June
2021.
14. Villafana T, et al. Passive and active immunization against
respiratory syncytial virus for the young and old. Expert Rev
Vaccines. 2017;16:1-39.
15. 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
16. Centers for Disease Control and Prevention. Vaccines &
Immunizations. August 18, 2017.
https://www.cdc.gov/vaccines/vac-gen/immunity-types.htm. Accessed
June 2021.
Adrian Kemp
Company Secretary
AstraZeneca PLC
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