The LOI is a critical step in ensuring
patients living with PNH or aHUS have public access to
Ultomiris, the first and only long-acting C5 complement
inhibitor
MISSISSAUGA, ON,
Oct. 24,
2023 /CNW/ - Alexion Pharma Canada Corp.,
AstraZeneca's Rare Disease group, has entered into a Letter of
Intent (LOI) with the pan-Canadian Pharmaceutical Alliance (pCPA)
for Ultomiris (ravulizumab) for the treatment of adult
patients with paroxysmal nocturnal hemoglobinuria (PNH) and
the treatment of adult and paediatric patients one month of age and
older with atypical hemolytic uremic syndrome (aHUS) to inhibit
complement-mediated thrombotic microangiopathy. With the LOI
in place with the pCPA, individual provinces and territories may
now initiate the process to list Ultomiris on their
formularies, the timing for which will vary by province and
territory.
PNH is a rare, chronic, progressive and potentially
life-threatening blood disorder. It is characterised by red blood
cell destruction within blood vessels (also known as intravascular
haemolysis) and white blood cell and platelet activation, which can
result in thrombosis (blood clots). 1-3
aHUS is a progressive, chronic condition with relapses. It is a
type of thrombotic microangiopathy, which is a group of severe and
potentially life-threatening rare disorders that cause blood clots
and damage to the walls of the smallest blood vessels. The blood
clots can cause injury to organs that may lead to organ failure and
death.6-9
"In many countries around the world, ravulizumab is first-line
therapy for most patients with PNH. We're pleased to see that the
path is now clear for patients in Canada to soon have publicly funded access as
well," said Dr. Christopher
Patriquin, MD, MSc, FRCPC, Chair of the Canadian PNH
Network.
"The Canadian Association of PNH Patients welcomes the recent
decision by the pCPA to enable Canadian patients to join PNH
patients from many other countries around the world who are
already experiencing the benefits of ravulizumab. Our
hope now is that provinces and territories quickly follow suit and
provide reimbursement for this treatment," said Barry Katsof, Founder & President of the
Canadian Association of PNH Patients.
"aHUS Canada is pleased that the pCPA has come to an agreement
to make ravulizumab publicly available to aHUS patients in
Canada. Having a choice in
treatment is very valuable to the aHUS community. It's important
that ravulizumab be listed soon on all provincial and
territorial formularies so patients can live their lives to the
fullest," said Michael Eygenraam,
Chair, aHUS Canada.
Gaby Bourbara, General Manager of Alexion Canada, said: "We would like to thank
participating jurisdictions within the pCPA for their partnership
in recognizing the need for this important innovation for Canadians
living with PNH, as well as those with aHUS. It is critical that
progress is made on the implementation of Canada's rare disease
strategy and that patients have access to the therapies they need
to live healthier lives. We look forward to our ongoing
collaboration with provincial, territorial and federal
jurisdictions to finalize listing agreements to better serve the
rare disease community."
Notes
PNH
PNH is a rare, chronic, progressive and potentially
life-threatening blood disorder. It is characterised by red blood
cell destruction within blood vessels (also known as intravascular
haemolysis) and white blood cell and platelet activation, which can
result in thrombosis (blood clots). 1-3
PNH is caused by an acquired genetic mutation that may happen
any time after birth and results in the production of abnormal
blood cells that are missing important protective blood cell
surface proteins. These missing proteins enable the complement
system, which is part of the immune system and is essential to the
body's defence against infection, to 'attack' and destroy or
activate these abnormal blood cells.1 Living with
PNH can be debilitating, and signs and symptoms may include blood
clots, abdominal pain, difficulty swallowing, erectile dysfunction,
shortness of breath, excessive fatigue, anaemia and dark-coloured
urine.1,4,5
aHUS
aHUS is a type of thrombotic microangiopathy, which is a group
of severe and potentially life-threatening rare disorders that
cause blood clots and damage to the walls of the smallest blood
vessels. The blood clots can cause injury to organs, that may lead
to organ failure and death.6-9 Signs, symptoms and
complications of TMA include organ damage, such as to the kidneys,
heart, brain, and/or other organs; shortness of breath; high blood
pressure; thrombosis (blood clots); low platelet count; anaemia;
fatigue, confusion and bruising.6,8-14
aHUS is a progressive, chronic condition with relapses. It
is caused by a combination of genetic and/or environmental factors
resulting in dysregulation of the complement system, which is
part of the body's immune system and essential to the
body's defence against infection. It may appear in the
presence or absence of a "trigger" or co-existing
condition.15-19
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 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. 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.
References
- Brodsky RA. Paroxysmal nocturnal hemoglobinuria. Blood.
2014;124(18):2804-2811.
- Griffin M, Hillmen P, Munir T, et al. Significant hemolysis is
not required for thrombosis in paroxysmal nocturnal hemoglobinuria.
Haematologica. 2019;104(3):e94-e96.
- Hillmen P., et al. The Complement Inhibitor Eculizumab in
Paroxysmal Nocturnal Hemoglobinuria. N Engl J Med.
2006;355(12):1233-43.
- Hillmen, P., et al. Effect of the complement inhibitor
eculizumab on thromboembolism on patients with paroxysmal nocturnal
hemoglobinuria. Blood. 2007;110(12):4123-4128.
- Kulasekararaj, AG, Hill A, Rottinghaus ST, et al. Ravulizumab
(ALXN1210) vs eculizumab in C5-inhibitor-experienced adult patients
with PNH: the 302 study. Blood. 2019;133(6):540–549.
- Arnold D, Patriquin C, Nazy I. Thrombotic microangiopathies: a
general approach to diagnosis and management. Canadian Medical
Association Journal. 2017. 189 (4):153-159.
- Blasco M, Guillén-Olmos E, et al. Complement Mediated
Endothelial Damage in Thrombotic Microangiopathies. Frontiers in
Medicine. 2022. 9:1-12.
- Barbour T, John S, Cohney S, et al. Thrombotic microangiopathy
and associated renal disorders. Nephrology Dialysis
Transplantation. 2012. 27(7):2673–2685.
- Blasco M, Guillèn E, et. al. Thrombotic microangiopathies
assessment: mind the complement. Clinical Kidney Journal.
2020. 14(4):1055-1066.
- Greenbaum L, Licht C, Nikolaou V, et al. Functional Assessment
of Fatigue and Other Patient-Reported Outcomes in Patients Enrolled
in the Global aHUS Registry. Kidney International Reports.
2020. 5:1161-1171.
- Timmermans S, Abdul-Hamid M, et al. Patients with
hypertension-associated thrombotic microangiopathy may present with
complement abnormalities. Kidney International. 2017. 91(6):
1420-1425.
- Thomas M, Robinson S, Scully M.
How we manage thrombotic microangiopathies in pregnancy.
British Journal of Haematology. 2016. 173(6) 821-830.
- Meri S. Complement activation in diseases presenting with
thrombotic microangiopathy. European Journal of Internal
Medicine. 2013. 24(6):496-502.
- Sridharan M, Abraham R, Amer H, et al. Atypical Hemolytic
Uremic Syndrome-Clinical Presentation, Treatment, and Short Term
Outcomes: The Mayo Clinic Experience.
- Jokiranta, TS. HUS and atypical HUS. Clinical Platelet
Disorders. 2017. 129(21).
- Asif, A., Nayer, A. & Haas, C.S. Atypical hemolytic uremic
syndrome in the setting of complement-amplifying conditions: case
reports and a review of the evidence for treatment with eculizumab.
J Nephrol. 2017. 30, 347–362.
- Afshar-Kharghan, V. Atypical hemolytic uremic syndrome.
Hematology Am Soc Hematol Educ Program. 2016 (1):
217–225.
- Brambilla, M, Ardissino, G, Paglialonga, F, et al.
Haemoglobinuria for the early identification of aHUS relapse: data
from the ItalKId-HUS Network. J Nephrol. 2022. 35, 279–284.
- Merle, N. S., et al. Complement System Part II: Role in
immunity. Frontiers of Immunology. 2015. 6:257.
SOURCE Alexion AstraZeneca Rare Disease