REG - AstraZeneca PLC - Ultomiris approved in the US for NMOSD

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25/03/2024 07:00

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RNS Number : 0545I  AstraZeneca PLC  25 March 2024

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
(https://onlinelibrary.wiley.com/doi/10.1002/ana.26626) .(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
(https://www.astrazeneca.com/media-centre/press-releases/2023/ultomiris-approved-in-japan-for-the-prevention-of-relapses-in-patients-with-nmosd.html)
and the European Union (EU)
(https://www.astrazeneca.com/media-centre/press-releases/2023/ultomiris-approved-in-the-eu-for-adults-with-neuromyelitis-optica-spectrum-disorder-nmosd.html)
. 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 (http://www.astrazeneca.com/) and follow the
Company on social media @AstraZeneca
(https://www.linkedin.com/company/astrazeneca/mycompany/verification/) .

 

Contacts

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.

 

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
(https://classic.clinicaltrials.gov/ct2/show/NCT04201262) . Accessed March
2024.

 

Dr. Pittock has provided consulting services to Alexion.

 

Adrian Kemp

Company Secretary

AstraZeneca PLC

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