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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Ultomiris approved in EU for gMG
23 September 2022 07:00 BST
Ultomiris approved
in Europe for the treatment of adults with generalised myasthenia
gravis
First and only long-acting C5 inhibitor has demonstrated early
onset and sustained clinical benefit, and may reduce treatment
burden with dosing every 8 weeks
Improvement in activities of daily living seen across broad range
of patients, including those with milder symptoms
Ultomiris (ravulizumab)
has been approved in Europe as an add-on to standard therapy for
the treatment of adult patients with generalised myasthenia gravis
(gMG) who are anti-acetylcholine receptor (AChR)
antibody-positive.
This decision marks the first and only approval for a long-acting
C5 complement inhibitor for the treatment of gMG in Europe.
gMG is a rare, debilitating, chronic, autoimmune neuromuscular
disease that leads to a loss of muscle function and severe
weakness.1 The
diagnosed prevalence of gMG in the EU is estimated at approximately
89,000.2-8
The approval by the European Commission follows
the positive
opinion of the Committee
for Medicinal Products for Human Use and is based on results from
the CHAMPION-MG Phase III trial, which were
published online in NEJM
Evidence. In the
trial, Ultomiris was superior to placebo in the primary
endpoint of change from baseline in the Myasthenia
Gravis-Activities of Daily Living Profile (MG-ADL) total score at
Week 26, a patient-reported scale that assesses patients' abilities
to perform daily activities.9 Additionally,
in prolonged follow-up results from the open-label extension,
clinical benefit of Ultomiris was observed through 60
weeks.9
Renato Mantegazza, Professor at the Department of Neuroimmunology
and Neuromuscular Diseases, Fondazione IRCCS Istituto Neurologico
Carlo Besta, Milan, Italy, and CHAMPION-MG trial investigator,
said: "As physicians, we see first-hand how gMG can have a
debilitating impact on quality of life. Today's approval is a major
advancement for treating gMG in Europe, offering patients and
physicians a new, long-acting treatment option which has shown
reliable efficacy and sustained improvements in activities of daily
living."
Marc Dunoyer, Chief Executive Officer, Alexion, said: "This
approval in Europe of the first and only long-acting C5 inhibitor
is an important step towards realising our vision of improving the
lives of people living with gMG and increasing access
to Ultomiris worldwide. Alexion's pioneering leadership
in complement science has affirmed C5 inhibition as a proven
approach for managing this debilitating disease. We're proud to
offer a new treatment option that provides more convenience in
dosing and has shown clinical benefit in a broader range of
patients, including those who remain symptomatic despite their
initial standard of care treatment."
In CHAMPION-MG, the safety profile of Ultomiris was
comparable to placebo and consistent with that observed in Phase
III trials of Ultomiris in
paroxysmal nocturnal haemoglobinuria (PNH) and atypical haemolytic
uraemic syndrome (aHUS). The most common adverse reactions in
patients receiving Ultomiris were
diarrhoea, upper respiratory tract infection, nasopharyngitis
and headache.9
Ultomiris was approved in
the US in April 2022 and Japan in
August 2022 for certain adults with gMG. Regulatory reviews are
ongoing in additional countries.
Notes
gMG
gMG is a rare autoimmune disorder characterised by loss
of muscle function and severe muscle weakness.1
Eighty percent of people with gMG are AChR antibody positive
meaning they produce specific antibodies (anti-AChR) that bind to
signal receptors at the neuromuscular junction (NMJ), the
connection point between nerve cells and the muscles they
control.1,3,4,10,11 This
binding activates the complement system, which is essential to the
body's defence against infection, causing the immune system to
attack the NMJ.1 This
leads to inflammation and a breakdown in communication between the
brain and the muscles.1
gMG can occur at any age, but it most commonly begins for women
before the age of 40 and for men after the age of
60.12-14 Initial
symptoms may include slurred speech, double vision, droopy eyelids,
and lack of balance; these can often lead to more severe symptoms
as the disease progresses such as, impaired swallowing, choking,
extreme fatigue and respiratory failure.15,16
CHAMPION-MG
The global Phase III randomised, double-blind, placebo-controlled,
multicentre 26-week trial evaluated the safety and efficacy
of Ultomiris in adults with gMG. The trial enrolled 175
patients across North America, Europe, Asia-Pacific, and Japan.
Participants were required to have a confirmed myasthenia gravis
diagnosis at least six months prior to the screening visit with a
positive serologic test for anti-AChR antibodies, MG-ADL total
score of at least 6 at trial entry and Myasthenia Gravis Foundation
of America Clinical Classification Class II to IV at screening.
Patients could stay on stable standard of care medicines, with a
few exceptions, for the duration of the randomised control
period.17
Patients were randomised 1:1 to receive Ultomiris or placebo for a total of 26 weeks. Patients
received a single weight-based loading dose on Day 1, followed by
regular weight-based maintenance dosing beginning on Day 15, every
eight weeks. The primary endpoint of change from baseline in the
MG-ADL total score at Week 26 was assessed along with multiple
secondary endpoints evaluating improvement in disease-related and
quality-of-life measures.
Patients who completed the randomised control period were eligible
to continue into an open-label extension period evaluating the
safety and efficacy of Ultomiris, which is ongoing.
Ultomiris
Ultomiris (ravulizumab),
the first and only long-acting C5 complement inhibitor, offers
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
gMG.
Ultomiris is also approved
in the US, EU and Japan for the treatment of certain adults with
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 aHUS to inhibit
complement-mediated thrombotic microangiopathy.
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
nearly 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 Twitter @AstraZeneca.
Contacts
For details on how to contact the Investor Relations Team, please
click here.
For Media contacts, click here.
References
1. Howard,
J. F., (2017). Myasthenia gravis: the role of complement at the
neuromuscular junction. Annals of The New York Academy of Sciences,
1412(1), 113-128.
2. Westerberg
E, Punga AR. Epidemiology of Myasthenia Gravis in Sweden 2006-2016.
Brain Behav. 2020;10:e01819. https://doi.org/10.1002/brb3.1819
3. Anil,
R., Kumar, A., Alaparthi, S., Sharma, A., Nye, JL., Roy, B.,
O'Connor, KC., Nowak, R., (2020). Exploring outcomes and
characteristics of myasthenia gravis: Rationale, aims and design of
registry - The EXPLORE-MG registry. J Neurol Sci. 2020 Jul
15;414:116830.
4. Oh
SJ., (2009). Muscle-specific receptor tyrosine kinase antibody
positive myasthenia gravis current status. Journal of Clinical
Neurology. 2009b Jun 1;5(2):53-64.
5. Fang,
F., Sveinsson O., Thormar G., Granqvist M., Askling J., Lundberg
IE., Ye W., (2015). The autoimmune spectrum of myasthenia gravis: a
Swedish population-based study. J Intern Med 2015;
277:594-604.
6. Lefter,
S., Hardiman, O., Ryan, A., (2017). A population-based
epidemiologic study of adult neuromuscular disease in the Republic
of Ireland. Neurology 2017;88:304-313.
7. Pallaver,
F., Riviera, AP., Piffer, S., Ricciardi, R., Roni, R., Orrico, D.,
Bonifati, DM., (2011). Change
in Myasthenia Gravis Epidemiology in Trento, Italy, after Twenty
Years. Neuroepidemiology
2011;36:282-287.
8. Santos,
E., Coutinho, E., Moreira, I., et.al., (2016). Epidemiology
of Myasthenia Gravis in Northern Portugal: Frequency Estimates and
Clinical Epidemiological Distribution of Cases. Muscle Nerve 2016;
54: 413-421.
9. Ultomiris, European
Product Information, September 2022.
10. Tomschik,
M., Hilger, E., Rath, J., Mayer, EM., Fahrner, M., Cetin, H.,
Löscher, W., Zimprich, F., (2020). Subgroup stratification and
outcome in recently diagnosed generalized myasthenia gravis.
Neurology. 2020 Sep 8;95(10):e1426-e1436.
11. Hendricks,
TM., Bhatti, MT., Hodge, D., Chen, J., (2019). Incidence,
Epidemiology, and Transformation of Ocular Myasthenia Gravis: A
Population-Based Study. Am J Ophthalmol. 2019
Sep;205:99-105.
12. Myasthenia
Gravis. National Organization for Rare Disorders (NORD).
Available here.
Accessed March 2022.
13. Howard,
J. F., (2015). Clinical Overview of MG.
Available here.
Accessed March 2022.
14. Sanders,
D. B., Raja, S. M., Guptill J. T., Hobson-Webb, L. D., Juel, V. C.,
& Massey, J. M., (2020). The Duke myasthenia gravis clinic
registry: I. Description and demographics. Muscle & Nerve,
63(2), 209-216.
15. Myasthenia
Gravis Fact Sheet. (2020, April 27). National Institutes of
Neurological Disorders and Stroke. Available here.
Accessed March 2022.
16. Ding,
J., Zhao, S., Ren, K., Dang, D., Li, H., Wu, F., Zhang, M., Li, Z.,
& Guo, J., (2020). Prediction of generalization of ocular
myasthenia gravis under immunosuppressive therapy in Northwest
China. BMC Neurology, 20(238).
17. ClinicalTrials.gov.
Safety and Efficacy Study of Ravulizumab in Adults With Generalized
Myasthenia Gravis. NCT Identifier: NCT03920293.
Available here.
Accessed March 2022.
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.
