REG - AstraZeneca PLC - Ultomiris recommended for NMOSD EU approval

AstraZenecaAnnouncement

03/04/2023 07:00

For best results when printing this announcement, please click on link below:
http://newsfile.refinitiv.com/getnewsfile/v1/story?guid=urn:newsml:reuters.com:20230403:nRSC0382Va&default-theme=true

RNS Number : 0382V  AstraZeneca PLC  03 April 2023

3 April 2023 07:00 BST

 

Ultomiris recommended for approval in the EU by CHMP for the treatment of
adults with neuromyelitis optica spectrum disorder (NMOSD)

 

No relapses observed in pivotal trial of first and only long-acting C5
inhibitor, indicating potential to prevent long-term disability due to
relapses

 

Ultomiris (ravulizumab) has been recommended for marketing authorisation in
the European Union (EU) for the treatment of adult patients with neuromyelitis
optica spectrum disorder (NMOSD) who are anti-aquaporin-4 (AQP4) antibody
positive (Ab+). If authorised, Ultomiris would be the first and only approved
long-acting C5 complement inhibitor for the treatment of AQP4 Ab+ NMOSD in the
EU.

 

The Committee for Medicinal Products for Human Use (CHMP) of the European
Medicines Agency based its positive opinion on results from the CHAMPION-NMOSD
(https://www.astrazeneca.com/media-centre/press-releases/2022/ultomiris-showed-zero-relapses-in-adults-with-neuromyelitis-optica-spectrum-disorder-nmosd-with-median-treatment-duration-of-73-weeks.html)
Phase III trial.(1) In the CHAMPION-NMOSD 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. Notably, data showed 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), and continuing through a median duration
of 90 weeks.(1)

 

NMOSD is a rare and debilitating autoimmune disease that affects the central
nervous system (CNS), including the spine and optic nerves.(2-4) 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.(5-7) The diagnosed prevalence of adults with NMOSD in the EU is
estimated at approximately 6,000.(8,9)

 

Orhan Aktas, MD, Professor at the Department of Neurology, Medical Faculty at
Heinrich-Heine-University, Düsseldorf, Germany, said: "Even one NMOSD relapse
can lead to devastating long-term effects like vision loss, chronic pain and
paralysis, which underscores the need for treatment innovations that help
prevent relapses and optimise disease management. The sustained relapse risk
reduction observed in the CHAMPION-NMOSD Phase III trial supports the critical
role this long-acting C5 complement inhibitor may have for the NMOSD
community."

 

Marc Dunoyer, Chief Executive Officer, Alexion, said: "Today's positive
opinion advances our commitment to transform outcomes for patients with rare
neurological diseases and reflects the exceptional efficacy of C5 inhibition
in reducing the risk of life-altering relapses in NMOSD. For patients with
AQP4 Ab+ NMOSD, Ultomiris, the first and only long-acting C5 complement
inhibitor, may have the potential to eliminate relapses, while also offering a
convenient treatment schedule of infusions every eight weeks. We look forward
to the European Commission decision as we work to make Ultomiris available to
people living with NMOSD in the EU and around the world."

 

Overall, the safety and tolerability of Ultomiris were consistent with
previous clinical studies and real-world use. No new safety signals were
observed. The most common adverse events (AEs) were COVID-19, headache, back
pain, arthralgia and urinary tract infection. All cases of COVID-19 were
non-serious and considered to be unrelated to Ultomiris.(1)

 

Regulatory submissions for Ultomiris for the treatment of NMOSD are also
currently under review with multiple health authorities, including in the
United States (US) and Japan.

 

Notes

 

NMOSD
NMOSD is a rare disease in which the immune system is inappropriately
activated to target healthy tissues and cells in the CNS.(2,3) Approximately
three-quarters of people with NMOSD are anti-AQP4 Ab+, meaning they produce
antibodies that bind to a specific protein, aquaporin-4 (AQP4).(10) 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.(2,8,11)

 

NMOSD most commonly affects women and begins in the mid-30s. Men and children
may also develop NMOSD, but it is even more rare.(12,13) 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.(4-6,14,15 )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.(5-7) NMOSD is a distinct
disease from other CNS diseases, including multiple sclerosis. The journey to
diagnosis can be long, with the disease sometimes misdiagnosed.(16-18)

 

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.(19)

 

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), 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 and Japan for the treatment of certain
adults with generalised myasthenia gravis.

 

Ultomiris is also approved in the US, EU and Japan 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 and Japan for certain
adults and children with atypical haemolytic uraemic syndrome 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 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
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

For details on how to contact the Investor Relations Team, please click here
(https://www.astrazeneca.com/investor-relations.html#Contacts) . For Media
contacts, click here (https://www.astrazeneca.com/media-centre/contacts.html)
.

 

References

 

1.   Pittock SJ, Barnett M et al. Efficacy and safety of ravulizumab in
adults with anti-aquaporin-4 antibody-positive neuromyelitis optica spectrum
disorder: outcomes from the phase 3 CHAMPION-NMOSD trial. American Academy of
Neurology Annual Meeting, Abstract S5.002
(https://index.mirasmart.com/aan2023/SearchResults.php?Program_Number=S5.002)
.

2.   Wingerchuk DM, Lennon VA, Lucchinetti CF, Pittock SJ, Weinshenker BG.
The spectrum of neuromyelitis optica. Lancet Neurol. 2007;6(9):805-815.

3.   Wingerchuk DM. Diagnosis and treatment of neuromyelitis optica.
Neurologist. 2007;13(1):2-11.

4.   Hamid SHM, Whittam D, Mutch K 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.

5.   Wingerchuk DM, Weinshenker BG. Neuromyelitis optica. Curr Treat Options
Neurol. 2008;10(1):55-66.

6.   Kitley J, Leite MI, Nakashima I, 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.

7.   Jarius S, Ruprecht K, Wildemann B, et al. Contrasting disease patterns
in seropositive and seronegative neuromyelitis optica: a multicentre study of
175 patients. J Neuroinflamm. 2012;9:14.

8.   Cossburn, M., et al. (2012). The Prevalence of Neuromyelitis Optica in
South East Wales. Eur J Neurol., 19(4): 655-659.

9.   Miyamoto K., et al. (2018). Nationwide Epidemiological Study of
Neuromyelitis Optica in Japan. J Neurol Neurosurg Psychiatry, 89(6):667-68.

10.  Wingerchuk DM, Hogancamp WF, O'Brien PC, Weinshenker BG. The clinical
course of neuromyelitis optica (Devic's syndrome). Neurology.
1999;53(5):1107-1114.

11.  Papadopoulos MC, Bennett JL, Verkman AS. Treatment of neuromyelitis
optica: state-of-the-art and emerging therapies. Nat Rev Neurol.
2014;10(9):493.

12.  Takata K, Matsuzaki T, Tajika Y. Aquaporins: water channel proteins of
the cell membrane. Prog Histochem Cytochem. 2004;39(1):1-83.

13.  Mori M, Kuwabara S, Paul F. Worldwide prevalence of neuromyelitis optica
spectrum disorders. J Neurol Neurosurg Psychiatry. 2018 Jun;89(6):555-556.
doi: 10.1136/jnnp-2017-317566. Epub 2018 Feb 7. PMID: 29436488.

14.  Quek AML, Mckeon A, Lennon VA et al. Effects of age and sex on
aquaporin-4 autoimmunity. Arch Neurol 2012 and 69:1039-43.

15.  Tüzün E, Kürtüncü M, Türkoğlu R, et al. Enhanced complement
consumption in neuromyelitis optica and Behcet's disease patients. J
Neuroimmunol. 2011;233(1-2):211-215.

16.  Kuroda H, Fujihara K, Takano R, et al. Increase of complement fragment
C5a in cerebrospinal fluid during exacerbation of neuromyelitis optica. J
Neuroimmunol. 2013;254(1-2):178-182.

17.  Jarius, S., Wildemann, B. (2013). The History of Neuromyelitis Optica. J
Neuroinflammation 10, 797.

18.  Mealy, M. A., et al. (2019). Assessment of Patients with Neuromyelitis
Optica Spectrum Disorder Using the EQ-5D. International journal of MS care,
21(3), 129-134.

19.  ClinicalTrials.gov. An Efficacy and Safety Study of Ravulizumab in Adult
Participants With NMOSD. NCT Identifier: NCT04201262. Available online.
Accessed September 2022.

 

Adrian Kemp

Company Secretary

AstraZeneca PLC

This information is provided by RNS, the news service of the London Stock Exchange. RNS is approved by the Financial Conduct Authority to act as a Primary Information Provider in the United Kingdom. Terms and conditions relating to the use and distribution of this information may apply. For further information, please contact
rns@lseg.com (mailto:rns@lseg.com)
 or visit
www.rns.com (http://www.rns.com/)
.

RNS may use your IP address to confirm compliance with the terms and conditions, to analyse how you engage with the information contained in this communication, and to share such analysis on an anonymised basis with others as part of our commercial services. For further information about how RNS and the London Stock Exchange use the personal data you provide us, please see our
Privacy Policy (https://www.lseg.com/privacy-and-cookie-policy)
.   END  RESUPUBACUPWUBG