Ultomiris transforms the treatment landscape
for AQP4 Ab+ NMOSD patients, with potential to eliminate relapses
and improve outcomes
MISSISSAUGA, ON, Nov. 1, 2023
/CNW/ - Ultomiris (ravulizumab) has been approved by Health
Canada 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
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This approval comes following the CHAMPION-NMOSD Phase III
trial, which was published online in the Annals of
Neurology and selected as an abstract of distinction at
the 2023 American Academy of Neurology Annual Meeting.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 adjudicated relapses were observed among
Ultomiris patients with a median treatment duration of 73
weeks.
NMOSD is a rare 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
Galina Vorobeychik, MD, Clinical
Associate Professor (Neurology) at the University of British Columbia and Director at the
Fraser Health Multiple Sclerosis Clinic at Burnaby Hospital, said:
"NMOSD is a rare disease that has significant impact on patients'
lives. I am hopeful that the approval of this new therapy will
improve the future outlook of those living with NMOSD in
Canada. The huge benefits are
that the amount of ravulizumab is determined by a patient's weight
and infused once every eight weeks which allows patients to travel
and maintain their regular life between infusions."
Sumaira Ahmed, an NMOSD patient
herself and the founder and Executive Director of The Sumaira
Foundation, said: "The approval of ravulizumab for NMOSD represents
a therapy option that works via the immune system complement
pathway, with a much less frequent infusion dosing schedule of once
every eight weeks. This represents a real innovation and
improvement for our patient community, greatly simplifying
work/life balance, travel plans, and the daily lived experience for
NMOSD patients. Patients can vary in their response to medicines,
so having a wider range of therapy options to choose from is very
important to patients and clinicians in successfully managing this
rare but serious condition."
Gaby Bourbara, General Manager of Alexion
Canada, said: "We are thrilled that Canadians living with
NMOSD now have a new therapy option to help them manage this
challenging disease. We look forward to partnering with key
stakeholders and payer partners across the country to ensure it is
reimbursed. It is critical that progress is made on the
implementation of Canada's rare disease strategy and that patients
have accelerated access to innovative therapies they need to live
healthier lives."
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. All cases of COVID-19
were non-serious and considered to be unrelated to
Ultomiris.2
Ultomiris is currently approved for the treatment of
certain adults with NMOSD in the European Union (EU), Japan and other 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 Specific serum anti-aquaporin-4 antibodies
(AQP4-ab) are pathogenic and identified in most patients with NMOSD
and this means they produce antibodies that bind to
AQP4.9 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.3,10,11
It has been found that NMOSD is more common in women and the
average age of onset is early 30s to mid-40s.13 People
with NMOSD may experience optic neuritis, which causes pain in the
eye and vision loss, transverse myelitis which causes weakness or
paralysis of arms and legs, numbness, loss of bladder and bowel
control, severe nausea and vomiting and subsequent hiccups from
involvement of a part of the brain that controls
vomiting.14 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.15-17
CHAMPION-NMOSD
CHAMPION-NMOSD is a global Phase III, open-label, multi-centre
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.18
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.
Further, Ultomiris is approved in the 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 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. Please visit https://alexion.com/worldwide/canada.
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 www.astrazeneca.ca and follow the Company on X
@AstraZenecaCA.
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SOURCE Alexion AstraZeneca Rare Disease