REG - AstraZeneca PLC - Ultomiris approved in EU for gMG

AstraZenecaAnnouncement

23/09/2022 07:00

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RNS Number : 4292A  AstraZeneca PLC  23 September 2022

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
(https://www.astrazeneca.com/media-centre/press-releases/2022/ultomiris-recommended-for-approval-in-the-eu-by-chmp.html)
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
(https://evidence.nejm.org/doi/full/10.1056/EVIDoa2100066) 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
(https://www.astrazeneca.com/media-centre/press-releases/2022/ultomiris-approved-in-the-us-for-adults-with-generalised-myasthenia-gravis.html)
in April 2022 and Japan
(https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2022/ultomiris-approved-in-japan-for-the-treatment-of-adults-with-generalised-myasthenia-gravis.html)
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 (http://www.astrazeneca.com/) and follow the
Company on Twitter @AstraZeneca (https://twitter.com/AstraZeneca) .

 

Contacts

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(https://www.astrazeneca.com/investor-relations.html#Contacts) . For Media
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.

 

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
(https://urldefense.com/v3/__https:/doi.org/10.1002/brb3.1819__;!!OR9aRoiw!N8Czx5L3JhTwloOC73InuJBtf25Axs-v0_TYTy0mMzALOlg57yP_EZrF6huByabTEaz2Kid2Z0HF3AW51vJmK60B$)

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 (https://rarediseases.org/rare-diseases/myasthenia-gravis/) .
Accessed March 2022.

13.  Howard, J. F., (2015). Clinical Overview of MG. Available here
(https://myasthenia.org/Professionals/Clinical-Overview-of-MG) . 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
(https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Myasthenia-Gravis-Fact-Sheet)
. 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 (https://clinicaltrials.gov/ct2/show/NCT03920293) . Accessed March 2022.

 

 

Adrian Kemp

Company Secretary

AstraZeneca PLC

 

 

 

 

 

 

 

 

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