REG - AstraZeneca PLC - Ultomiris approved in Japan for gMG

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25/08/2022 07:16

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RNS Number : 1480X  AstraZeneca PLC  25 August 2022

25 August 2022 07:10 BST

 

Ultomiris approved in Japan for the treatment of adults with generalised
myasthenia gravis

 

First and only long-acting C5 complement inhibitor offers early onset and
sustained efficacy, and has the potential to reduce treatment burden with
dosing every 8 weeks

 

Ultomiris (ravulizumab) has been approved in Japan for the treatment of adult
patients with generalised myasthenia gravis (gMG) who are anti-acetylcholine
receptor (AChR) antibody-positive and whose symptoms are difficult to control
with high-dose intravenous immunoglobulin therapy (IVIg) or plasmaphaeresis.
Japan's Pharmaceuticals and Medical Devices Agency also indicated that
Ultomiris can be considered for patients who cannot receive high-dose IVIg or
plasmaphaeresis due to complications, adverse reactions or other limiting
factors.

 

The approval of the first and only long-acting C5 complement inhibitor by the
Japanese Ministry of Health, Labour and Welfare (MHLW) was based on positive
results from the CHAMPION-MG Phase III trial, which showed 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.(1) Additionally, in prolonged follow-up results from the
open-label extension, clinical benefit of Ultomiris was observed through 60
weeks.(1)

 

gMG is a rare, debilitating, chronic, autoimmune neuromuscular disease that
leads to a loss of muscle function and severe weakness.(2) The diagnosed
prevalence of gMG in Japan is estimated at approximately 22,000.(3)

 

Hiroyuki Murai, MD, PhD, Professor and Chairman, Department of Neurology,
School of Medicine, International University of Health and Welfare, Narita,
Japan, said: "C5 inhibition is a proven approach to manage gMG. The approval
of Ultomiris is an important advance for the gMG community in Japan, offering
patients and physicians a new long-acting C5 inhibitor that has demonstrated
sustained improvement in activities of daily living through 60 weeks, with
fewer infusions per year over current treatment."

 

Marc Dunoyer, Chief Executive Officer, Alexion, said: "We are pleased that
Ultomiris is now approved in Japan for adults with gMG, a disease that may
impact their ability to work, meet family obligations and live their lives
fully. The approval speaks to the strength and consistency of Ultomiris
clinical data as demonstrated in the global CHAMPION-MG Phase III trial. We
look forward to bringing this treatment option to people living with gMG in
Japan as part of our broader strategy to expand global access to our
medicines."

 

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 nausea, headache and diarrhoea.(1)

Results from the CHAMPION-MG trial were published online
(https://evidence.nejm.org/doi/full/10.1056/EVIDoa2100066)  in NEJM
Evidence and presented at the 2022 American Academy of Neurology Annual
Meeting in April.

 

Ultomiris was approved in the US
(https://www.astrazeneca.com/media-centre/press-releases/2022/ultomiris-approved-in-the-us-for-adults-with-generalised-myasthenia-gravis.html)
for adults with anti-AChR antibody-positive gMG in April, and regulatory
reviews are ongoing in additional countries. It was recently recommended for
marketing authorisation in the European Union as an add-on to standard therapy
for the treatment of adult patients with gMG who are anti-AChR
antibody-positive.

 

Notes

 

gMG

gMG is a rare autoimmune disorder characterised by loss of muscle function and
severe muscle weakness.(2)

 

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.(2,4-7) This binding activates the complement system,
which is essential to the body's defence against infection, causing the immune
system to attack the NMJ.(2) This leads to inflammation and a breakdown in
communication between the brain and the muscles.(2)

 

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.(8-10) 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.(11,12)

 

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.(13)

 

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 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 (http://www.astrazeneca.com/) and follow the
Company on Twitter @AstraZeneca (https://twitter.com/AstraZeneca) .

 

Contacts

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.

 

References

1.   Ultomiris (ravulizumab) Japanese prescribing information; 2022.

2.   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.

3.   Lai, CH., Tseng, HK., (2010). Nationwide Population-Based
Epidemiological Study of Myasthenia Gravis in Taiwan. Neuroepidemiology. 2010
June;35:66-71. 7.

4.   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.

5.   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.

6.   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.

7.   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.

8.   Myasthenia Gravis. National Organization for Rare Disorders (NORD).
Available here (https://rarediseases.org/rare-diseases/myasthenia-gravis/) .
Accessed March 2022.

9.   Howard, J. F., (2015). Clinical Overview of MG. Available here
(https://myasthenia.org/Professionals/Clinical-Overview-of-MG) . Accessed
March 2022.

10.  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.

11.  Myasthenia Gravis Fact Sheet. (2020, April 27). National Institutes of
Neurological Disorders and Stroke. Available here
(https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Myasthenia-Gravis-Fact-Sheet)
. Accessed March 2022.

12.  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).

13.  ClinicalTrials.gov. Safety and Efficacy Study of Ravulizumab in Adults
With Generalized Myasthenia Gravis. NCT Identifier: NCT03920293. Available
here (https://clinicaltrials.gov/ct2/show/NCT03920293) . Accessed March 2022.

 

Adrian Kemp

Company Secretary

AstraZeneca PLC

 

 

 

 

 

 

 

 

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