“Extensive clinical data and real-world clinical experience spanning
more than 10 years further establish the benefits that Soliris is
providing to patients with PNH,” said Leonard Bell, M.D., Chief
Executive Officer of Alexion. “The presentation of the two-year aHUS
data also demonstrates the continued benefits of long-term Soliris
therapy in patients with aHUS, and underscores the important role of
hematologists in diagnosing and treating patients with this severe and
ultra-rare complement-mediated disease.”
Ten-Year Experience with Soliris in All Patients with PNH Treated in
In a poster presentation today, researchers presented data from all 153
patients who participated in a nationally commissioned PNH service led
by two UK medical centers. The objective of the study was to describe
the long-term safety, efficacy, and outcomes in patients with PNH from
the UK who received Soliris treatment from May 2002 to April 2012.
The results demonstrated that the significant clinical benefits and
long-term safety of Soliris were sustained over 10 years of chronic
treatment. The investigators reported that long-term Soliris treatment
led to an improvement in survival when compared with historical
controls, and a significant reduction in the incidence of TE.
Researchers also reported data on the effect of discontinuation of
anti-coagulant therapy in selected PNH patients. Transfusion
independence was observed in the majority of patients, and the number of
units transfused was significantly reduced in those patients still
receiving transfusions. Results also confirmed the long-term safety and
efficacy of continuous Soliris treatment.
Researchers presented the following data in support of these conclusions:
Long-term Soliris therapy significantly reduced intravascular
hemolysis by 83.4%, as assessed by levels of LDH (p<0.001).
The researchers noted that UK patients on long-term Soliris therapy
had improved survival compared with previously published historical
8,9 Researchers also compared the survival of PNH
patients treated with Soliris to a normal population of the same age
and gender. Although the survival of PNH patients after 10 years of
Soliris therapy was slightly inferior to this normal healthy
population group, the causes of death in PNH patients were related to
bone marrow failure and not due to hemolysis or TE associated with the
In the 12 months prior to starting Soliris, 36 thrombotic episodes
were reported in 22 patients. None of those patients had a further
thrombotic episode while on Soliris therapy. In the most recent 12
months on therapy, TEs were significantly reduced with only 3 events
reported in a total of 3 patients (p<0.05).
Of 117 patients transfused in the 12 months before receiving Soliris,
77 (65.8%) were transfusion-independent in the most recent 12 months
on treatment. Among those patients still receiving transfusions
(n=40), there was a significant 69% reduction in the number of units
transfused, from a median of 26 units, 12 months before therapy, to 8
units in the most recent 12 months on therapy (P<0.05).
“More than 10 years of experience in the UK show the continuing profound
positive impact of Soliris on the lives of patients living with PNH.
With Soliris therapy, PNH-related morbidities are significantly reduced,
and in addition to this positive efficacy, there is continuing safety as
well as highly significant improvement in symptoms and quality of life,”
said Anita Hill
, M.D. Ph.D., lead author of the poster and
Consultant Haematologist at the Leeds Teaching Hospitals, Leeds, UK.
Long-Term Safety of Sustained Soliris Treatment in Patients with PNH
In a poster presentation on December 8, researchers presented results of
a long-term safety analysis in 195 patients receiving continuous Soliris
treatment (mean duration: 30.3 months) in the Soliris PNH clinical
development trials and associated extension studies. They compared the
reported incidence of adverse events (AEs), irrespective of relation to
treatment, during the first 26 weeks of Soliris treatment with the
reported incidence of AEs in the last 26 weeks.
The study demonstrated the long-term safety of Soliris in PNH patients
treated for up to 5.5 years, with no evidence of cumulative toxicity.
Further, the incidence of patients reporting an AE in the last 26 weeks
of treatment was significantly reduced compared with the incidence in
the first 26 weeks (p<0.001). Additionally, the probability of a patient
experiencing an AE decreased significantly with time (p<0.001). There
was also a low rate of meningococcal infection with long-term Soliris
treatment (0.422 per 100 patient-years). Two patients experienced
meningococcal infections from strains not covered by their vaccinations.
Both infections were successfully treated and both resolved without
sequelae. Four patient deaths were reported over the course of the
study; none were considered by the investigators to be related to
“Our data give us even greater confidence in the long-term safety of
Soliris in patients with PNH,” stated lead investigator Jeffrey Szer
M.D., Professor/Director of the Department of Clinical Haematology at
Royal Melbourne Hospital in Melbourne, Australia. “The adverse event
rate among patients on continuous Soliris therapy suggests a favorable
risk-to-benefit ratio over the long term.”
Reduced Risk of Thromboembolism (TE): An International PNH Registry
In a separate poster presentation today, researchers reported that
Soliris is associated with a reduced risk of TE and mortality, based on
findings from 1047 patients enrolled in an international PNH registry.
Over a mean follow-up period of 22.5 months, patients receiving Soliris
treatment had a cumulative incidence of TE of 0.41% at one year and
1.35% at two years. Among patients not taking Soliris, the corresponding
one- and two-year incidences of TE were 1.70% and 2.61%, respectively.
The cumulative incidence of mortality in Soliris-treated patients was
2.31% and 4.21% at one and two years, respectively, while in untreated
patients it was 4.40% and 7.01%, respectively. The study authors noted
that results of these analyses and the conclusions that can be drawn
from them are limited due to small number of TE and mortality outcomes.
“The International PNH Registry provides real-world data that are
consistent with prior research which indicated a reduced risk of
thromboembolism and mortality in patients treated with Soliris,” said
, M.D., Ph.D., lead author of the poster and
Professor of Haematology at Hospital Saint Louis, APHP, University Paris
VII Denis Diderot, Paris, France.
Other PNH Data Presentations
The ASH meeting also featured the following data presentations in
patients with PNH:
Soliris in Patients with aHUS
In a poster presentation on December 8, researchers in South Korea
evaluated the risk of TE in patients with PNH and elevated hemolysis
(as identified by LDH ≥1.5 x ULN) in addition to any of the four
clinical symptoms of abdominal pain, chest pain, dyspnea, or
hemoglobinuria, compared with patients who had elevated LDH alone. The
analyses confirm that elevated hemolysis was associated with a
seven-fold increased risk of TE in patients with PNH. The risk of TE
was significantly further increased in patients with elevated
hemolysis and additional symptoms of abdominal pain, chest pain,
dyspnea or hemoglobinuria compared with patients without the symptom
and LDH <1.5 x ULN. These results underscore the importance of early
therapeutic intervention and monitoring of PNH patients with elevated
In a separate poster presentation on December 8, data supported the
need to test high-risk PNH patients for diagnostic markers as an aid
to treatment selection. Researchers presented an updated analysis of
7,699 high-risk patients whose blood cells were screened for a PNH
clone using high-sensitivity flow cytometry. Among the 481
PNH-positive patients, those with large PNH clone sizes (>20%) were
found to be more likely to have clinical symptoms, particularly those
associated with hemolysis, and were thus deemed more likely to benefit
A poster presentation today identified a polymorphism in the terminal
complement protein C5 that appears to be associated with no or minimal
reduction in LDH in nine Japanese patients with PNH who received
Soliris therapy, although there is no evidence of the mutation outside
of Japan or in any other Asian populations. The study authors
concluded that further research is needed to verify that the
polymorphism in the C5 gene is responsible for the suboptimal
reduction in LDH and to determine a more accurate prevalence of this
C5 polymorphism in Japanese populations.
During the ASH annual meeting, researchers presented two-year data that
highlight the long-term benefits of chronic Soliris therapy in patients
with aHUS. As presented last month at the annual meeting of the American
Society of Nephrology (ASN)
, data from two pivotal phase 2
studies demonstrated that ongoing Soliris treatment for two years was
associated with sustained ongoing inhibition of complement-mediated TMA,
as indicated by a maintained increase in platelet count, and sustained
improvement in renal function and TMA event-free status.
In a poster presented on December 8, researchers presented two-year
findings from a prospective, open-label, single-arm phase 2 trial of
Soliris in adult and adolescent patients with a long duration of aHUS
and chronic kidney damage who were undergoing prolonged plasma exchange
or plasma infusion (PE/PI) before starting treatment with Soliris.
Patients had been diagnosed with aHUS a median of 48 months prior to
starting the study. Twenty patients were enrolled in the initial study
and received Soliris for 26 weeks. Nineteen of the 20 patients continued
into a long-term extension phase. Patients were evaluated for a median
duration of 114 weeks.
The study achieved its primary endpoint, TMA event-free status (at least
12 consecutive weeks of stable platelet count, no PE/PI, and no new
dialysis), in 16 of 20 (80%) patients through 26 weeks. TMA event-free
status was achieved and maintained by 95% of patients through two years,
indicating that chronic treatment with Soliris continued to
significantly inhibit complement-mediated TMA. Patients achieved and
maintained TMA event-free status regardless of the identification of a
genetic complement mutation. Importantly, no patient required new
dialysis and only one patient required any PE/PI through data cutoff.
In patients treated with Soliris over two years, researchers observed
continued improvement in renal function, including a sustained
improvement in estimated glomerular filtration rate (eGFR), with a mean
change from baseline of 6.1 mL/min/1.73m
through 26 weeks
(p=0.0001) and 7.2 mL/min/1.73m
through two years (p<0.05).
Earlier intervention with Soliris therapy was associated with greater
increases in eGFR (p=0.001). Seven of 20 patients (35%) experienced
chronic kidney disease (CKD) improvement of at least one stage by 26
weeks, compared with 12 of 20 patients (60%) by two years.
In a poster presented on December 9, researchers presented two-year
follow-up data from a prospective, open-label, single-arm phase 2 study
in 17 adult and adolescent patients with aHUS who had presented with
progressive clinical TMA complications despite intensive PE/PI. Patients
had been diagnosed with aHUS for a median of 10 months before the start
of the study. Seventeen patients were enrolled in the initial study and
received Soliris for 26 weeks. Seventeen patients continued into a
long-term extension phase. Patients were evaluated for a median duration
of 100 weeks.
The study achieved its primary endpoint, as mean platelet count improved
from baseline at 26 weeks (p=0.0001). Additionally, the improved
platelet count continued over two years (p<0.001), indicating sustained
inhibition of complement-mediated TMA with ongoing eculizumab treatment.
Platelet normalization (≥150x10
/L) was achieved in 13 of 15
patients (87%) who had low platelets at baseline by 26 weeks and was
maintained through two years for 12 of the 13 patients. TMA event-free
status was also achieved rapidly and maintained through two years, with
15 of 17 (88%) Soliris-treated patients achieving TMA event-free status
through each data cut-off point (26 weeks, one year, and two years), and
TMA event-free status was achieved regardless of the identification of a
genetic complement mutation.
“These longer-term data demonstrate the sustained benefits of Soliris
therapy in patients with aHUS and reveal a significant and continued
improvement in renal function over time,” commented Larry Greenbaum
M.D., Ph.D., Director of Pediatric Nephrology at Emory University and
Children's Healthcare of Atlanta, who presented the aHUS poster on
December 9. “Further, the data support that earlier treatment leads to
even better outcomes for patients with aHUS.”
PNH is an ultra-rare blood disorder in which chronic, uncontrolled
activation of complement, a component of the normal immune system,
results in hemolysis (destruction of the patient's red blood cells). PNH
strikes people of all ages, with an average age of onset in the early
Approximately 10% of all patients first develop
symptoms at 21 years of age or younger.
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.
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.
PNH has been identified more
commonly among patients with disorders of the bone marrow, including
aplastic anemia (AA) and myelodysplastic syndromes (MDS).
In patients with thrombosis of unknown origin, PNH may be an underlying
aHUS is a chronic, ultra-rare, and life-threatening disease in which a
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.
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
Sixty-five percent of all patients with
aHUS require kidney dialysis, have permanent kidney damage or die within
the first year after diagnosis despite plasma exchange or plasma
The majority of patients with aHUS who
receive a kidney transplant commonly experience subsequent systemic TMA,
resulting in a 90% transplant failure rate in these TMA patients.
aHUS affects both children and adults.
TMA also causes reduction in platelet count (thrombocytopenia) and red
blood cell destruction (hemolysis). While mutations have been identified
in at least ten different complement regulatory genes, mutations are not
identified in 30-50% of patients with a confirmed diagnosis of aHUS.
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, European Union, Japan and other
countries as the first and only treatment for patients with paroxysmal
nocturnal hemoglobinuria (PNH), a debilitating, ultra-rare and
life-threatening blood disorder, characterized by complement-mediated
hemolysis (destruction of red blood cells). Soliris is indicated to
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