a0626i
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 March 2024
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.
Ultomiris approved in the US for NMOSD
25 March 2024
Ultomiris approved in
the US for the treatment of adults with neuromyelitis optica
spectrum disorder (NMOSD)
First and only long-acting C5 complement inhibitor offers patients
with AQP4 Ab+ NMOSD the potential to live relapse-free
Unprecedented relapse risk reduction observed in CHAMPION-NMOSD
trial underscores how Ultomiris may redefine patient journey for
rare neurological disease
Ultomiris (ravulizumab-cwvz) has been approved in the
United States (US) as the first and only long-acting C5 complement
inhibitor for the treatment of adult patients with anti-aquaporin-4
(AQP4) antibody-positive (Ab+) neuromyelitis optica spectrum
disorder (NMOSD).1
The approval by the US Food and Drug Administration (FDA) was based
on positive results from the CHAMPION-NMOSD Phase III trial, which
were published in the Annals
of Neurology.2 In
the trial,
Ultomiris was compared to
an external placebo arm from the pivotal Soliris PREVENT clinical
trial.
Ultomiris met the primary
endpoint of time to first on-trial relapse as confirmed by an
independent adjudication committee. Zero relapses were
observed among Ultomiris patients with a median treatment duration of
73 weeks (relapse risk reduction: 98.6%, hazard ratio (95% CI):
0.014 (0.000, 0.103), p<0.0001).2
NMOSD is a rare and debilitating autoimmune disease that affects
the central nervous system (CNS), including the spine and optic
nerves.3-5 Most
people living with NMOSD experience unpredictable relapses,
characterised by a new onset of neurologic symptoms or worsening of
existing neurologic symptoms, which tend to be severe and recurrent
and may result in permanent disability.6-8 The
diagnosed prevalence of adults with NMOSD in the US is estimated at
approximately 6,000.9-11
Sean J. Pittock, MD, Director of Mayo Clinic's Center for Multiple
Sclerosis and Autoimmune Neurology and of Mayo's Neuroimmunology
Laboratory and lead primary investigator in the CHAMPION-NMOSD
trial, said: "C5 inhibition has been proven to offer efficacy in
reducing the risk of NMOSD relapses by blocking the complement
system, a part of the immune system, from attacking healthy cells
in the spinal cord, optic nerve and brain. With today's FDA
approval, patients now have the
option of a long-acting C5 inhibitor treatment that showed zero
relapses in the pivotal
CHAMPION-NMOSD trial, supporting the primary goal of relapse
prevention in treating NMOSD."
Marc Dunoyer, Chief Executive Officer, Alexion, said: "Alexion has
been at the forefront of innovation in NMOSD, striving to offer
patients a future without fear of life-altering or even fatal
relapses. Building on the established efficacy of C5 inhibition for
people living with AQP4 Ab+ NMOSD, we are proud to deliver a
transformative, long-acting treatment option that has the potential
to eliminate relapses with a convenient dosing schedule every eight
weeks. We are grateful to the NMOSD community for their ongoing
collaboration and input, which enables us to advance science for
rare diseases."
Overall, the safety and tolerability of Ultomiris in the CHAMPION-NMOSD trial were consistent
with previous clinical studies and real-world use, and no new
safety signals were observed. The most common adverse events (AEs)
were COVID-19, headache, back pain, arthralgia and urinary tract
infection.2
Ultomiris is also approved
for certain adults with NMOSD in Japan and
the European Union
(EU). Regulatory reviews are
ongoing in additional countries.
Notes
NMOSD
NMOSD is a rare disease in which the immune system is
inappropriately activated to target healthy tissues and cells in
the CNS.3,4 Approximately
three-quarters of people with NMOSD are anti-AQP4 Ab+, meaning they
produce antibodies that bind to a specific protein, aquaporin-4
(AQP4).5,12 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.3,13,14
It most commonly affects women and begins in the mid-30s. Men and
children may also develop NMOSD, but it is even more
rare.15,16 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.5-7,17,18 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.6-8 NMOSD
is a distinct disease from other CNS diseases, including multiple
sclerosis. The journey to diagnosis can be long, with the disease
sometimes misdiagnosed.19-21
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.22
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, Japan and other countries for the treatment of certain
adults with generalised myasthenia gravis
(gMG).
Ultomiris is also approved
in the US, EU, Japan and other countries 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, Japan and other
countries for certain adults and children with atypical haemolytic
uraemic syndrome to inhibit complement-mediated thrombotic
microangiopathy (aHUS).
Further, Ultomiris is approved in the US, 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 70 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.
Ultomiris (ravulizumab-cwvz) US prescribing information;
2024.
2. Pittock,
SJ, et al. Ravulizumab in aquaporin-4-positive neuromyelitis optica
spectrum disorder. Ann
Neurol,
2023; 93: 1053-1068.
3. Wingerchuk
DM, et al. The spectrum of neuromyelitis
optica. Lancet
Neurol.
2007;6(9):805-815.
4. Wingerchuk
DM. Diagnosis and treatment of neuromyelitis
optica. Neurologist.
2007;13(1):2-11.
5. 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.
6. Wingerchuk
DM, et al. Neuromyelitis optica. Curr Treat
Options Neurol.
2008;10(1):55-66.
7. 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.
8. Jarius
S, et al. Contrasting disease patterns in seropositive and
seronegative neuromyelitis optica: a multicentre study of 175
patients. J
Neuroinflammation.
2012;9:14.
9.
Papp V, et al. A population-based epidemiological study of
neuromyelitis optica spectrum disorder in Hungary. Eur J Neurol.
2020;27(2):308-317.
10.
Flanagan EP, et al. Epidemiology of aquaporin-4 autoimmunity and
neuromyelitis optica spectrum. Ann Neurol.
2016;79:775-783.
11.
Bukhari W, et al. Incidence and Prevalence of NMOSD in Australia
and New Zealand. J Neurol Neurosurg Psychiatry.
2017;88(8):632-638.
12. Wingerchuk
DM, et al. The clinical course of neuromyelitis optica (Devic's
syndrome). Neurology.
1999;53(5):1107-1114.
13. Cossburn
M, et al. The Prevalence of Neuromyelitis Optica in South East
Wales. Eur J
Neurol.
2012;19(4): 655-659.
14. Papadopoulos
MC, et al. Treatment of neuromyelitis optica: state-of-the-art and
emerging therapies. Nat Rev
Neurol.
2014;10(9):493.
15. Takata
K, et al. Aquaporins: water channel proteins of the cell
membrane. Prog
Histochem Cytochem.
2004;39(1):1-83.
16. Mori
M, et al. Worldwide prevalence of neuromyelitis optica spectrum
disorders. J Neurol
Neurosurg Psychiatry.
2018;89(6):555-556.
17. Quek
AML, et al. Effects of age and sex on aquaporin-4
autoimmunity. Arch
Neurol.
2012;69:1039-43.
18. Tüzün
E, et al. Enhanced complement consumption in neuromyelitis optica
and Behcet's disease patients. J
Neuroimmunol.
2011;233(1-2):211-215.
19. 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.
20. Jarius
S, et al.. The History of Neuromyelitis
Optica. J
Neuroinflammation. 2013;10,
797.
21. 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.
22. ClinicalTrials.gov.
An Efficacy and Safety Study of Ravulizumab in Adult Participants
With NMOSD. NCT Identifier: NCT04201262.
Available here.
Accessed March 2024.
Dr. Pittock has provided consulting services to
Alexion.
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:
25 March 2024
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
|