REG - AstraZeneca PLC - Ultomiris NMOSD Ph. III trial met primary endpoint

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05/05/2022 07:00

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RNS Number : 3777K  AstraZeneca PLC  05 May 2022

5 May 2022 07:00 BST

 

Ultomiris met primary endpoint in CHAMPION-NMOSD Phase III trial in adults
with neuromyelitis optica spectrum disorder

 

Zero adjudicated relapses observed among Ultomiris patients over a median
treatment duration of 73 weeks

 

Positive high-level results from the open-label Phase III CHAMPION-NMOSD trial
showed that Ultomiris (ravulizumab-cwvz) achieved a statistically significant
and clinically meaningful reduction in the risk of relapse in adults with
anti-aquaporin-4 (AQP4) antibody-positive (Ab+) neuromyelitis optica spectrum
disorder (NMOSD) compared to the external placebo arm from the pivotal Soliris
PREVENT clinical trial.

 

Ultomiris, the first and only long-acting C5 complement inhibitor, met the
primary endpoint of time to first on-trial relapse, as confirmed by an
independent adjudication committee. Notably, no relapse was observed in 58
patients over a median treatment duration of 73 weeks.

 

NMOSD is a rare and devastating autoimmune disease that affects the central
nervous system (CNS), including the spine and optic nerves.(1-3) Most people
living with NMOSD often experience unpredictable relapses, a new onset of
neurologic symptoms or worsening of existing neurologic symptoms, also
referred to as attacks, which tend to be severe and recurrent and may result
in permanent disability.(4-6)( )

 

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: "Every NMOSD relapse
can have debilitating and irreversible consequences, so reducing relapses is
critical. Patients on Ultomiris remained relapse free over a median treatment
duration of 73 weeks in the trial."

 

Marc Dunoyer, Chief Executive Officer, Alexion, said: "Soliris established the
role of complement inhibition in preventing relapses in NMOSD, and with
Ultomiris, we continue to innovate for patients with a more convenient every
eight-week dosing schedule. These trial results show that Ultomiris may help
patients move towards eliminating relapses, which is an important advancement
in the treatment of NMOSD."

 

The safety and tolerability of Ultomiris in the Champion-NMOSD trial were
consistent with previous clinical studies and other approved indications.
Fifty-six patients are continuing to receive treatment in a long-term
extension period, which is ongoing.

The data will be presented at a forthcoming medical meeting and submitted to
global health authorities as rapidly as possible to bring forward Ultomiris to
the NMOSD community.

Notes

 

NMOSD

NMOSD is a rare disease in which the immune system is inappropriately
activated to target healthy tissues and cells in the CNS.(1,2) Approximately
three-quarters of people with NMOSD are anti-AQP4 Ab+, meaning they produce
antibodies that bind to a specific protein, aquaporin-4 (AQP4).(7) 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.(1,8,9)

 

It most commonly affects women and begins in the mid-30s. Men and children may
also develop NMOSD, but it is even more rare.(10,11) People with NMOSD may
experience vision problems, intense pain, loss of bladder/bowel function,
abnormal skin sensations (eg, tingling, prickling or sensitivity to heat/cold)
and impact on coordination and/or movement.(3-5,12,13) 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.(4-6) NMOSD is a distinct disease from other CNS
diseases, including multiple sclerosis. The journey to diagnosis can be long,
with the disease sometimes misdiagnosed.(14-16

)

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.(17)

 

Due to the potential long-term functional impact of NMOSD relapses, 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, 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
generalised myasthenia gravis.

 

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

 

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

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

3.   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.

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

5.   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.

6.   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.

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

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

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

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

11.  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.

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

13.  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.

14.  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.

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

16.  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.

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

 

Dr. Pittock has provided consulting services to Alexion.

 

Adrian Kemp

Company Secretary

AstraZeneca PLC

 

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