REG - AstraZeneca PLC - Ultomiris approved in the US for adults with gMG

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28/04/2022 07:15

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RNS Number : 6675J  AstraZeneca PLC  28 April 2022

28 April 2022 07:00 BST

 

Ultomiris approved in the US for adults with generalised myasthenia gravis

 

First and only long-acting C5 complement inhibitor to demonstrate clinical
improvement in patients with generalised myasthenia gravis

 

Ultomiris showed early effect and lasting improvement in activities of daily
living and has potential to reduce treatment burden with dosing every 8 weeks

 

Ultomiris (ravulizumab-cwvz) has been approved in the US for the treatment of
adult patients with generalised myasthenia gravis (gMG) who are
anti-acetylcholine receptor (AChR) antibody-positive, which represents 80% of
people living with the disease.(1-5)

 

The approval by the Food and Drug Administration (FDA) was based on positive
results from the CHAMPION-MG Phase III trial, in which 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)

 

This FDA action marks the first and only approval for a long-acting C5
complement inhibitor for the treatment of gMG.

 

gMG is a rare, debilitating, chronic, autoimmune neuromuscular disease that
leads to a loss of muscle function and severe weakness.(6) The diagnosed
prevalence of gMG in the US is estimated at approximately 90,000.(7)

 

Professor James F. Howard, Jr, MD, Department of Neurology at The University
of North Carolina School of Medicine and lead primary investigator in the
CHAMPION-MG trial said: "Despite recent advances, managing gMG is complex.
Earlier intervention can preserve function and quality of life. This approval
offers patients, including those with milder symptoms, a long-acting C5
inhibitor with early onset and reliable efficacy."

 

Samantha Masterson, Chief Executive Officer, Myasthenia Gravis Foundation of
America (MGFA), said: "gMG takes a physical and emotional toll on those living
with the disease. We are grateful for continued innovation and research into
new treatment and dosing options to meet the needs of more patients and reduce
the treatment burden. With the approval of Ultomiris, we're excited that MG
patients now have another option to consider as part of their personalised
treatment strategies that may offer more convenience and improve muscle
weakness."

 

Marc Dunoyer, Chief Executive Officer, Alexion, said: "Since bringing forward
the first complement inhibitor, we've continued to listen to the community and
focused innovation on the needs of gMG patients. We're proud to deliver on
this commitment with today's approval. Ultomiris, the only long-acting C5
inhibitor, will benefit a broader range of patients, including those with
milder symptoms. As presented at the 2022 American Academy of Neurology Annual
Meeting, Ultomiris has demonstrated clinical benefit through 60 weeks, with
treatment every eight weeks, compared to Soliris every two weeks."

 

In the trial, 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 upper respiratory tract infection and diarrhoea.(1)

Results from the CHAMPION-MG trial were recently 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.

 

Regulatory submissions for Ultomiris for the treatment of gMG are currently
under review with multiple health authorities, including in the European Union
(EU) and Japan.

 

Notes

 

gMG

gMG is a rare autoimmune disorder characterised by loss of muscle function and
severe muscle weakness.(6)

 

Eighty per cent 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.(2-6) This binding activates the complement system, which
is essential to the body's defence against infection, causing the immune
system to attack the NMJ.(6) This leads to inflammation and a breakdown in
communication between the brain and the muscles.(6)

 

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-cwvz), 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 for the treatment of certain adults with gMG.

 

Ultomiris is also approved in the US, EU and Japan for the treatment of
certain adults and children with PNH.

 

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-cwvz) US prescribing information; 2022.

2.   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.

3.   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.

4.   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.

5.   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.

6.   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.

7.   Westerberg, E., Punga, A., (2020). Epidemiology of Myasthenia Gravis in
Sweden 2006-2016. Brain and behavior. 2020 Nov;10(11):e01819.

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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