a5429l
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 September 2023
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
Cambridge
CB2 0AA
United
Kingdom
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Update on US review of Ultomiris for NMOSD
6 September 2023
Update on US regulatory review
of Ultomiris in NMOSD
The US Food and Drug Administration (FDA) has issued
a complete response letter (CRL) regarding the supplemental
Biologics License Application (sBLA) for long-acting C5
complement inhibitor Ultomiris (ravulizumab-cwvz) for the treatment of
adult patients with neuromyelitis optica spectrum disorder (NMOSD)
who are anti-aquaporin-4 (AQP4) antibody positive
(Ab+).
The CRL did not request additional analysis or reanalysis of the
Phase III CHAMPION-NMOSD trial data included in the sBLA
submission and
did not raise concerns about the efficacy or safety data from the
trial.1
The FDA requested modifications to enhance
the Ultomiris Risk Evaluation and Mitigation Strategy
(REMS) to further validate
patients' meningococcal vaccination status or
prophylactic administration of antibiotics prior
to treatment.
Alexion, AstraZeneca Rare Disease is working closely with the FDA
regarding next steps for the REMS modifications and remains
committed to bringing Ultomiris to people living with NMOSD in the US as
quickly as possible.
Ultomiris is
currently approved for the treatment of certain adults with NMOSD
in the European Union (EU), Japan and other
countries.
Ultomiris is
approved by the FDA for the treatment of adult patients with
generalised myasthenia gravis (gMG) who are anti-acetylcholine
receptor (AChR) Ab+, and certain adults and children with
paroxysmal nocturnal haemoglobinuria (PNH) or atypical haemolytic
uraemic syndrome (aHUS).
Notes
NMOSD
NMOSD is a rare disease in which the immune system is
inappropriately activated to target healthy tissues and cells in
the central nervous system (CNS).2,3 Approximately
three-quarters of people with NMOSD are anti-AQP4 Ab+, meaning they
produce antibodies that bind to a specific protein, aquaporin-4
(AQP4).4 This
binding can inappropriately activate the complement system, which
is part of the immune system and is essential to the body's defence
against infection, to destroy cells in the optic nerve, spinal cord
and brain.2,5,6
It most commonly affects women and begins in the mid-30s. Men and
children may also develop NMOSD, but it is even more
rare.7,8 People
with NMOSD may experience vision problems, intense pain, loss of
bladder/bowel function, abnormal skin sensations (e.g., tingling,
prickling or sensitivity to heat/cold) and impact on coordination
and/or movement.9-13 Most
people living with NMOSD experience unpredictable relapses, also
known as attacks. Each relapse can result in cumulative
disability including vision loss, paralysis and sometimes premature
death.10,11,14 NMOSD
is a distinct disease from other CNS diseases, including multiple
sclerosis. The journey to diagnosis can be long, with the disease
sometimes misdiagnosed.15-17
CHAMPION-NMOSD
CHAMPION-NMOSD is a global Phase III, open-label, multicentre
trial evaluating the safety and efficacy
of Ultomiris in
adults with NMOSD. The trial enrolled 58 patients across North
America, Europe, Asia-Pacific and Japan. Participants were required
to have a confirmed NMOSD diagnosis with a positive anti-AQP4
antibody test, at least one attack or relapse in the twelve months
prior to the screening visit, an Expanded Disability Status Scale
Score of 7 or less and body weight of at least 40 kilograms at
trial entry. Participants could stay on stable supportive
immunosuppressive therapy for the duration of the
trial.18
Due to the potential long-term functional impact of NMOSD relapses
and available effective treatment options, a direct placebo
comparator arm was precluded for ethical reasons. The active
treatment was compared to an external placebo arm from the
pivotal Soliris PREVENT clinical trial.
Over a median treatment duration of 73 weeks, all enrolled patients
received a single weight-based loading dose
of Ultomiris on Day 1, followed by regular weight-based
maintenance dosing beginning on Day 15, every eight weeks. The
primary endpoint was time to first on-trial relapse, as confirmed
by an independent adjudication committee. The end of the primary
treatment period could have occurred either when all patients
completed or discontinued prior to the Week 26 visit and two or
more adjudicated relapses were observed, or when all patients
completed or discontinued prior to the Week 50 visit if fewer than
two adjudicated relapses were observed. In the trial, there were
zero adjudicated relapses, so the end of the primary treatment
period occurred when the last enrolled participant completed the
50-week visit.
Patients who completed the primary treatment period were eligible
to continue into a long-term extension period, which is
ongoing.
Ultomiris
Ultomiris (ravulizumab-cwvz),
the first and only long-acting C5 complement inhibitor, provides
immediate, complete and sustained complement inhibition. The
medication works by inhibiting the C5 protein in the terminal
complement cascade, a part of the body's immune system. When
activated in an uncontrolled manner, the complement cascade
over-responds, leading the body to attack its own healthy
cells. Ultomiris is administered intravenously every eight
weeks in adult patients, following a loading
dose.
Ultomiris is
approved in the US, EU and Japan for the treatment of certain
adults with generalised myasthenia gravis.
Ultomiris is
also approved in the US, EU and Japan for the treatment of certain
adults with paroxysmal nocturnal haemoglobinuria (PNH) and for
certain children with PNH in the US and EU.
Additionally, Ultomiris is approved in the US, EU and Japan for
certain adults and children with atypical haemolytic uraemic
syndrome to inhibit complement-mediated thrombotic
microangiopathy.
Further, Ultomiris is approved in the EU and Japan for the
treatment of certain adults with neuromyelitis optica spectrum
disorder (NMOSD).
As part of a broad development programme, Ultomiris is being assessed for the treatment of
additional haematology and neurology
indications.
Alexion
Alexion, AstraZeneca Rare Disease, is the group within AstraZeneca
focused on rare diseases, created following the 2021 acquisition of
Alexion Pharmaceuticals, Inc. As a leader in rare diseases for more
than 30 years, Alexion is focused on serving patients and families
affected by rare diseases and devastating conditions through the
discovery, development and commercialisation of life-changing
medicines. Alexion focuses its research efforts on novel molecules
and targets in the complement cascade and its development efforts
on haematology, nephrology, neurology, metabolic disorders,
cardiology and ophthalmology. Headquartered in Boston,
Massachusetts, Alexion has offices around the globe and serves
patients in more than 50 countries.
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 social media @AstraZeneca.
Contacts
For details on how to contact the Investor Relations Team, please
click here.
For Media contacts, click here.
References
1. Pittock
SJ, et al. Efficacy and safety of ravulizumab in adults with
anti-aquaporin-4 antibody-positive neuromyelitis optica spectrum
disorder: outcomes from the phase 3 CHAMPION-NMOSD trial. Oral
Presentation at: American Academy of Neurology Annual Meeting,
April 23, 2023; Presentation S5.002.
2. Wingerchuk
DM, et al. The spectrum of neuromyelitis
optica. Lancet
Neurol.
2007;6(9):805-815.
3. Wingerchuk
DM. Diagnosis and treatment of neuromyelitis
optica. Neurologist.
2007;13(1):2-11.
4. Wingerchuk
DM, et al. The clinical course of neuromyelitis optica (Devic's
syndrome). Neurology.
1999;53(5):1107-1114.
5. Cossburn
M, et al. The Prevalence of Neuromyelitis Optica in South East
Wales. Eur J
Neurol.
2012;19(4): 655-659.
6. Papadopoulos
MC, et al. Treatment of neuromyelitis optica: state-of-the-art and
emerging therapies. Nat Rev
Neurol.
2014;10(9):493.
7. Takata
K, et al. Aquaporins: water channel proteins of the cell
membrane. Prog
Histochem Cytochem.
2004;39(1):1-83.
8. Mori
M, et al. Worldwide prevalence of neuromyelitis optica spectrum
disorders. J Neurol
Neurosurg Psychiatry.
2018;89(6):555-556.
9. Hamid
SHM, et
al. What proportion of AQP4-IgG-negative NMO spectrum disorder
patients are MOG-IgG positive? A cross sectional study of 132
patients. J
Neurol.
2017;264(10):2088-2094.
10. Wingerchuk
DM, Weinshenker BG. Neuromyelitis optica. Curr Treat
Options Neurol.
2008;10(1):55-66.
11. Kitley
J, et al. Prognostic factors and disease course in aquaporin-4
antibody-positive patients with neuromyelitis optica spectrum
disorder from the United Kingdom and
Japan. Brain. 2012;135(6):1834-1849.
12. Quek
AML, et al. Effects of age and sex on aquaporin-4
autoimmunity. Arch
Neurol 2012;69:1039-43.
13. Tüzün
E, et al. Enhanced complement consumption in neuromyelitis optica
and Behcet's disease patients. J
Neuroimmunol.
2011;233(1-2):211-215.
14. Jarius S, et al. Contrasting disease
patterns in seropositive and seronegative neuromyelitis optica: a
multicentre study of 175 patients. J
Neuroinflammation. 2012;9:14.
15. Jarius
S, Wildemann B. The History of Neuromyelitis
Optica. J
Neuroinflammation. 2013;10,
797.
16. Kuroda
H, et al. Increase of complement fragment C5a in cerebrospinal
fluid during exacerbation of neuromyelitis
optica. J
Neuroimmunol.
2013;254(1-2):178-182.
17. Mealy
MA, et al. Assessment of Patients with Neuromyelitis Optica
Spectrum Disorder Using the EQ-5D. Int
J MS
Care.
2019;21(3), 129-134.
18. ClinicalTrials.gov.
An Efficacy and Safety Study of Ravulizumab in Adult Participants
With NMOSD. NCT Identifier: NCT04201262.
Available here.
Accessed August 2023.
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:
6 September 2023
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
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