Updated EU Label Supports Soliris Treatment
of Patients with PNH Regardless of History of Transfusion
Updated EU Label Reflects New aHUS Data on
Soliris Efficacy and Risks Associated with Discontinuing
Treatment
Alexion announced today that the Committee for Medicinal
Products for Human Use (CHMP) of the European Medicines Agency
(EMA) has adopted a Positive Opinion to update the therapeutic
indication for Soliris® (eculizumab) in the treatment of paroxysmal
nocturnal haemoglobinuria (PNH) for patients with high disease
activity regardless of history of transfusion. The CHMP also issued
a Positive Opinion to update the EU label for Soliris with
additional data on the benefits of long-term treatment and the
risks associated with treatment discontinuation in patients with
atypical haemolytic uremic syndrome (aHUS). If approval is granted,
updated information for the use of Soliris in both PNH and aHUS
will be detailed in the Summary of Product Characteristics (SmPC)
which will be published in the revised European Public Assessment
Report (EPAR).
“The positive CHMP opinion is an important milestone as it
underscores that complement-mediated haemolysis, and not
transfusions, is the key clinical indicator of the risk for
devastating and life-threatening consequences in patients with
PNH,” said Carsten Thiel, Ph.D., SVP, EMEA and Asia-Pacific,
Alexion. “We believe that, if approved by the European Commission,
the updated EU label will better guide physicians in assessing and
optimizing care for patients with this life-threatening and
ultra-rare disorder.”
About the PNH Label Update
PNH is a debilitating ultra-rare blood disorder with
life-threatening consequences.1-3 In patients with PNH, chronic,
uncontrolled activation of complement, a component of the natural
immune system, results in haemolysis (destruction of the patient's
red blood cells), leading to thrombosis, organ failure and
shortened survival.4-7
The CHMP based its opinion on efficacy and safety data from an
observational, non-interventional international PNH Registry, which
confirmed that patients with no history of transfusion who were
treated with Soliris had a significant reduction in haemolysis
(measured by LDH) and associated clinical symptoms, such as
fatigue.
Peter Hillmen, Professor of Experimental Haematology, University
of Leeds, and Honorary Consultant Haematologist at St James’s
University Hospital, Leeds and Chair of the Executive Committee of
the International PNH Registry, commented: “I am pleased that data
from the International PNH Registry are advancing our knowledge
about the underlying pathophysiology of PNH and the devastating
consequences for patients. It is very good news that these data
from the International PNH Registry have enabled an update to the
indication for eculizumab in PNH so that patients who are at high
risk of morbidities or premature mortality can benefit from
eculizumab, regardless of history of transfusion.”
About the aHUS Label Update
aHUS is a genetic, ultra-rare, and life-threatening disease in
which chronic uncontrolled complement activation results in
complement-mediated TMA, the formation of blood clots in small
blood vessels throughout the body.8,9 Permanent, uncontrolled
complement activation in aHUS causes a life-long risk for TMA,
which leads to sudden, catastrophic, and life-threatening damage to
the kidney, brain, heart, and other vital organs, and premature
death.8,10
If today’s CHMP positive opinion is approved by the EC, new
efficacy data will now be added to the aHUS section of the EU label
specifying that longer term treatment with Soliris was associated
with an increased percentage of patients who experienced clinically
meaningful improvements. Importantly, when Soliris treatment was
continued for more than 26 weeks, additional patients achieved
complete TMA response and haematologic normalization.
In addition, Section 4.4 of the EU label will include new
information on the risks associated with treatment discontinuation
in patients with aHUS.11 The CHMP based its opinion on additional
data from ongoing long-term follow-up studies of patients with aHUS
who had previously participated in the aHUS clinical trials. These
data showed that a proportion of the patients who discontinued
Soliris treatment and were followed for a median period of 24 weeks
experienced TMA following treatment discontinuation. Furthermore,
severe TMA complications occurred in additional patients who
received a reduced dosing regimen of Soliris outside of the
approved dosing regimen. Serious medical complications occurred in
these patients, including severe worsening of kidney function,
disease-related hospitalisation and progression to end-stage renal
disease requiring dialysis. These severe TMA complications occurred
in patients regardless of whether they had an identified genetic
mutation.
“The CHMP positive opinion recognizes the importance of
sustained Soliris treatment for patients with chronic complement
dysregulation and the ongoing risk of complement-mediated TMA and
organ damage in patients with aHUS,” said Camille L. Bedrosian,
M.D., Chief Medical Officer of Alexion. “If approved by the
European Commission, these important label updates will further
support the need for sustained terminal complement inhibition with
Soliris, even when clinical symptoms and lab values have
improved.”
Soliris is approved in nearly 50 countries as a treatment for
patients with PNH and in nearly 40 countries as a treatment for
patients with aHUS.
About PNH
PNH is an ultra-rare blood disorder in which chronic,
uncontrolled activation of complement, a component of the normal
immune system, results in haemolysis (destruction of the patient's
red blood cells). PNH strikes people of all ages, with an average
age of onset in the early 30s.12 Approximately 10% of all patients
first develop symptoms at 21 years of age or younger.13 PNH
develops without warning and can occur in men and women of all
races, backgrounds and ages. PNH often goes unrecognized, with
delays in diagnosis ranging from one to more than 10 years.14 In
the period of time before Soliris was available, it had been
estimated that approximately one-third of patients with PNH did not
survive more than five years from the time of diagnosis.12 PNH has
been identified more commonly among patients with disorders of the
bone marrow, including aplastic anemia (AA) and myelodysplastic
syndromes (MDS).15-17 In patients with thrombosis of unknown
origin, PNH may be an underlying cause.12
About aHUS
aHUS is a chronic, ultra-rare, and life-threatening disease in
which a life-long and permanent genetic deficiency in one or more
complement regulatory genes causes chronic, uncontrolled complement
activation, resulting in complement-mediated thrombotic
microangiopathy (TMA), the formation of blood clots in small blood
vessels throughout the body.8,9 Seventy-nine percent of all
patients with aHUS die, require kidney dialysis or have permanent
kidney damage within three years after diagnosis despite plasma
exchange or plasma infusion (PE/PI).18 Moreover, 33 to 40 percent
of patients die or progress to end-stage renal disease with the
first clinical manifestation of aHUS despite PE/PI.18,19 The
majority of patients with aHUS who receive a kidney transplant
commonly experience subsequent systemic TMA, resulting in a 90
percent transplant failure rate in these TMA patients.20
aHUS affects both children and adults. While mutations have been
identified in at least ten different complement regulatory genes,
mutations are not identified in 30-50 percent of patients with a
confirmed diagnosis of aHUS.18
About Soliris
Soliris is a first-in-class terminal complement inhibitor
developed from the laboratory through regulatory approval and
commercialization by Alexion. Soliris is approved in the US (2007),
European Union (2007), Japan (2010) and other countries as the
first and only treatment for patients with paroxysmal nocturnal
haemoglobinuria (PNH), a debilitating, ultra-rare and
life-threatening blood disorder, characterized by
complement-mediated hemolysis (destruction of red blood cells).
Soliris is indicated to reduce hemolysis.
Soliris is also approved in the US (2011), the European Union
(2011), Japan (2013) and other countries as the first and only
treatment for patients with atypical Haemolytic Uraemic Syndrome
(aHUS) to inhibit complement-mediated thrombotic microangiopathy, a
debilitating, ultra-rare and life-threatening genetic disorder
characterized by complement-mediated TMA (blood clots in small
vessels). For the breakthrough medical innovation in complement
inhibition, Alexion and Soliris have received the pharmaceutical
industry's highest honors: the 2008 Prix Galien USA Award for Best
Biotechnology Product with broad implications for future biomedical
research and the 2009 Prix Galien France Award in the category of
Drugs for Rare Diseases.
More information including the full prescribing information on
Soliris is available at:
http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000791/WC500054208.pdf
Important Safety Information
In Europe, the Summary of Product Characteristics (SmPC) for
Soliris includes a special warning and precaution for use: Due to
its mechanism of action, the use of Soliris increases the patient’s
susceptibility to meningococcal infection (Neisseria meningitidis).
These patients might be at risk of disease by uncommon serogroups
(particularly Y, W135 and X), although meningococcal disease due to
any serogroup may occur. To reduce the risk of infection, all
patients must be vaccinated at least 2 weeks prior to receiving
Soliris. aHUS patients who are treated with Soliris less than 2
weeks after receiving a meningococcal vaccine must receive
treatment with appropriate prophylactic antibiotics until 2 weeks
after vaccination. Patients must be re-vaccinated according to
current medical guidelines for vaccination use. Tetravalent
vaccines against serotypes A, C, Y and W135 are strongly
recommended, preferably conjugated ones. Vaccination may not be
sufficient to prevent meningococcal infection. Consideration should
be given to official guidance on the appropriate use of
antibacterial agents.
The most common or serious adverse reactions are headache
(occurred mostly in the initial phase), leukopenia and
meningococcal infection. The most common (>10%) adverse
reactions reported in paediatric aHUS patients were diarrhoea,
vomiting, pyrexia, upper respiratory tract infection and headache.
Soliris treatment should not alter anticoagulant management. Please
see Summary of Product Characteristics for full prescribing
information for Soliris, including all special warnings and
precautions.
About Alexion
Alexion is a biopharmaceutical company focused on serving
patients with severe and rare disorders through the innovation,
development and commercialization of life-transforming therapeutic
products. Alexion is the global leader in complement inhibition and
has developed and markets Soliris® (eculizumab), a treatment for
patients with paroxysmal nocturnal hemoglobinuria (PNH) and
atypical hemolytic uremic syndrome (aHUS), two debilitating,
ultra-rare and life-threatening disorders caused by chronic
uncontrolled complement activation. The treatment is currently
approved in nearly 50 countries for the treatment of PNH and in
nearly 40 countries for the treatment of aHUS. Alexion is
evaluating other potential indications for Soliris in additional
severe and ultra-rare disorders beyond PNH and aHUS, and is
developing other highly innovative biotechnology product
candidates, including asfotase alfa, across multiple therapeutic
areas.
Further information about Alexion can be found at:
www.alexionpharma.eu.
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AlexionMitali Rajan, +32 2 274 0065Associate Director, Corporate
Communications EMEArajanm@alxn.com
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