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Results of Phase 1b/2 Dose Regimen Optimization Studies for ALXN1210 in Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) Presented at American Society of Hematology (ASH) Meeting

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-- Data Demonstrate Rapid and Sustained Reduction of Plasma Lactate
Dehydrogenase (LDH) --

Alexion Pharmaceuticals, Inc. (NASDAQ:ALXN) announced today the
presentation of comprehensive dose-ranging data from two Phase 1b/2
studies of ALXN1210, the Company's investigational long-acting C5
complement inhibitor, in patients with paroxysmal nocturnal
hemoglobinuria (PNH), a chronic, progressive, debilitating and
potentially life-threatening ultra-rare blood disorder characterized by
complement-mediated hemolysis.1,2 Treatment with ALXN1210 for
up to eight months resulted in rapid and sustained reduction of plasma
lactate dehydrogenase (LDH) levels, a direct marker of hemolysis, with
reductions in mean LDH levels from Baseline (BL) ranging from 73% to
88%. ALXN1210 was generally well tolerated with a safety profile that is
consistent with that seen historically in patients with complement
inhibition.3 The data were presented at the 59th
American Society of Hematology (ASH) Annual Meeting & Exposition in
Atlanta. All patients from the Phase 1b study and from Cohorts 1, 2, and
3 of the Phase 2 study have been successfully transitioned to the Phase
3 dosing regimen, after which plasma LDH levels have remained suppressed.

"It is encouraging to see rapid and sustained reduction in plasma LDH
levels in these dose optimization studies," said Alexander Röth, M.D.
from the Department of Hematology, West German Cancer Center, University
Hospital Essen, Essen, Germany and an investigator in the Phase 1b/2
studies. "These comprehensive results provide robust preliminary
evidence for the efficacy and safety of ALXN1210 as a future treatment
for patients with PNH."

"The strength of these data and exposure-response analyses, along with
the totality of data for ALXN1210 and discussions with global
regulators, allowed us to determine an eight-week, weight-based dosing
regimen that targets complete C5 inhibition and rapid and sustained
suppression of LDH," said John Orloff, M.D., Executive Vice President
and Head of Research & Development at Alexion. "We have completed
enrollment in our two multinational Phase 3 PNH studies, with nearly 450
patients enrolled, and expect data from these studies in the second
quarter of 2018."

Optimization of Dose Regimen for ALXN1210, a Novel Complement C5
Inhibitor, in Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH):
Results of Two Phase 1b/2 Studies
3

The researchers presented results from two open-label Phase 1b/2 studies
designed to provide dose ranging data to optimize the dosing regimen for
the Phase 3 development of ALXN1210 as a treatment for patients with PNH
based on exposure-response assessments. The studies included a total of
39 adult patients with PNH (Study 103, n=13; Study 201, n=26) who were
naïve to complement inhibition. The primary efficacy endpoint was the
change from BL in mean plasma LDH levels to day 169 in Study 103 and day
253 in Study 201. The secondary efficacy endpoints were changes from BL
in free hemoglobin, haptoglobin, and reticulocytes. Post hoc efficacy
analyses evaluated the proportion of patients achieving LDH levels
within the normal range and the incidence of breakthrough hemolysis
(days 29-253). LDH BL was defined as the average of values at screening,
prior to the first ALXN1210 infusion. For other parameters, BL was
defined as the most recent value prior to the first infusion. Study 103
evaluated two escalating intravenous (IV) dosing regimens of ALXN1210,
and Study 201 evaluated four IV regimens with different doses and
intervals. The results demonstrated exposure-response relationships, and
further substantiate and extend previously presented results.4,5,6,7

    Study 201   Study 103
LDH at Protocol-Specified Endpointa   Cohort 1

1000 mg q4w

n=6

  Cohort 2

1600 mg q6w

n=6

  Cohort 3

2400 mg q8w

n=7

  Cohort 4

5400 mg q12w

n=7

  Cohort 1

900 mg q4w

n=6

  Cohort 2

1800 mg q4w

n=7

% LDH reduction from BL, mean (SD)b   72.9 (12.1)   77.8 (6.5)   85.0 (4.4)   87.6 (6.9)   86.0 (3.2)   84.7 (3.8)
LDH levels, U/L, mean (SD)   230.0 (44.0)   266.0 (54.3)   306.1 (130.7)   276.4 (196.9)   232.0 (82.3)   227.9 (50.6)
LDH normalization (D29-D253)c
LDH normalized, n/N (%)   5/6 (83)   3/6 (50)   4/7 (57)   5/7 (71)   4/6 (67)   6/7 (86)
LDH >1.5 x ULN, n/N (%)   4/6 (67)   3/6 (50)   2/7 (29)   3/7(43)   2/6 (33)   1/7 (14)
LDH >2 x ULN, n/N (%)   2/6 (33)   1/6 (17)   2/7 (29)   1/7 (14)   1/6 (17)   0/7 (0)
Breakthrough hemolysis (D29-253)d
Incidence of breakthrough hemolysis through day 253, n/N (%)   2/6 (33.3)   1/6 (16.7)   2/7 (28.6)   1/7 (14.3)   1/6 (16.7)   0/7 (0)

BL: baseline; SD: standard deviation; D: day; LDH: lactate
dehydrogenase; ULN: upper limit of normal
q4w: every 4 weeks; q6w:
every 6 weeks; q8w: every 8 weeks; q12w: every 12 weeks
a LDH
parameters at protocol-specified endpoint: Study 103, day 169/24 weeks;
Study 201, day 253/36 weeks.
b Primary efficacy endpoint.
c
Patients meeting each parameter at least once after day 29 through
day 253.
d Defined as at least 1 symptom or sign of
intravascular hemolysis (fatigue, abdominal pain, shortness of breath
[dyspnea], anemia [hemoglobin <10 g/dL and hemoglobin< baseline
hemoglobin], major adverse vascular event [including thrombosis],
dysphagia, or erectile dysfunction) within ±7 days of an elevated LDH ≥2
x ULN after prior LDH reduction to <1.5 x ULN on therapy.

The most frequent related treatment-emergent adverse event (TEAE) was
headache. No patient stopped treatment or withdrew from the studies, and
there were no deaths. Two patients in Study 201 experienced
meningococcal infections but recovered completely and continued
receiving ALXN1210. Meningococcal infections are a known risk with
terminal complement inhibition, and specific risk-management plans have
been in place for ten years for Soliris® (eculizumab) to minimize the
risk for patients.

About Paroxysmal Nocturnal Hemoglobinuria (PNH)

Paroxysmal nocturnal hemoglobinuria (PNH) is a chronic, progressive,
debilitating and potentially life-threatening ultra-rare blood disorder
that can strike men and women of all races, backgrounds, and ages
without warning, with an average age of onset in the early 30s.1,2,8
PNH often goes unrecognized, with delays in diagnosis ranging from one
to more than 10 years.2 In patients with PNH, chronic,
uncontrolled activation of the complement system, a component of the
body's immune system, results in hemolysis (the destruction of red blood
cells)9, which in turn can result in progressive anemia,
fatigue, dark urine and shortness of breath.10,11,12 The most
devastating consequence of chronic hemolysis is thrombosis (the
formation of blood clots), which can damage vital organs and cause
premature death.13 Historically, it had been estimated that
one in three patients with PNH did not survive more than five years from
the time of diagnosis.2 PNH is more common among patients
with disorders of the bone marrow, including aplastic anemia (AA) and
myelodysplastic syndromes (MDS).14,15,16 In certain patients
with thrombosis of unknown origin, PNH may be an underlying cause.9

About ALXN1210

ALXN1210 is an innovative, long-acting C5 inhibitor discovered and
developed by Alexion that works by inhibiting the C5 protein in the
terminal complement cascade, a part of the body's immune system that,
when activated in an uncontrolled manner, plays a role in severe
ultra-rare disorders like paroxysmal nocturnal hemoglobinuria (PNH),
atypical hemolytic uremic syndrome (aHUS), and anti-acetylcholine
receptor (AchR) antibody-positive myasthenia gravis (MG). In early
studies, ALXN1210 demonstrated rapid, complete, and sustained reduction
of free C5 levels, as well as rapid and sustained reduction of plasma
lactate dehydrogenase (LDH) levels, a direct marker of hemolysis (the
destruction of red blood cells).4,5,6,7 ALXN1210 is currently
being evaluated in Phase 3 clinical studies as a potential treatment for
patients PNH and aHUS, administered intravenously every eight weeks. In
addition, Alexion plans to initiate a single, pharmacokinetics
(PK)-based Phase 3 clinical study of ALXN1210 delivered subcutaneously
once per week as a potential treatment for patients with PNH and aHUS.

ALXN1210 has received Orphan Drug Designation (ODD) for the intravenous
treatment of patients with PNH in the U.S. and EU, and for the
subcutaneous treatment of patients with aHUS in the U.S.

About Soliris® (eculizumab)

Soliris® is a first-in-class complement inhibitor that works by
inhibiting the C5 protein in the terminal part of the complement
cascade, a part of the immune system that, when activated in an
uncontrolled manner, plays a role in severe rare and ultra-rare
disorders like paroxysmal nocturnal hemoglobinuria (PNH), atypical
hemolytic uremic syndrome (aHUS), and anti-acetylcholine receptor (AchR)
antibody-positive myasthenia gravis (MG). Soliris is approved in the
U.S., EU, Japan, and other countries as the first and only treatment for
patients with PNH and aHUS, in the EU as the first and only treatment of
refractory generalized MG (gMG) in adults who are anti-AchR
antibody-positive, and in the U.S. for the treatment of adult patients
with gMG who are anti-AchR antibody-positive. Alexion's new drug
application in Japan for Soliris as a treatment for patients with
anti-AchR antibody-positive refractory gMG has been accepted for review
by the Japanese Ministry of Health, Labour, and Welfare (MHLW). Soliris
is not indicated for the treatment of patients with Shiga-toxin E.
coli-related hemolytic uremic syndrome (STEC-HUS).

Soliris has received Orphan Drug Designation (ODD) for the treatment of
patients with PNH in the U.S., EU, Japan, and many other countries, for
the treatment of patients with aHUS in the U.S., EU, and many other
countries, for the treatment of patients with MG in the U.S. and EU, and
for the treatment of patients with refractory gMG in Japan. Alexion and
Soliris have received some of the pharmaceutical industry's highest
honors for the medical innovation in complement inhibition: the Prix
Galien USA (2008, Best Biotechnology Product) and France (2009, Rare
Disease Treatment).

For more information on Soliris, please see full prescribing information
for Soliris, including BOXED WARNING regarding risk of serious
meningococcal infection, available at www.soliris.net

Important Soliris Safety Information

The U.S. prescribing information for Soliris includes the following
warnings and precautions: Life-threatening and fatal meningococcal
infections have occurred in patients treated with Soliris. Meningococcal
infection may become rapidly life-threatening or fatal if not recognized
and treated early. Comply with the most current Centers for Disease
Control (CDC)'s Advisory Committee on Immunization Practices (ACIP)
recommendations for meningococcal vaccination in patients with
complement deficiencies. Immunize patients with meningococcal vaccines
at least two weeks prior to administering the first dose of Soliris,
unless the risks of delaying Soliris therapy outweigh the risk of
developing a meningococcal infection. Monitor patients for early signs
of meningococcal infections and evaluate immediately if infection is
suspected. Soliris is available only through a restricted program under
a Risk Evaluation and Mitigation Strategy (REMS). Under the Soliris
REMS, prescribers must enroll in the program. Enrollment in the Soliris
REMS program and additional information are available by telephone:
1-888-SOLIRIS (1-888-765-4747) or at www.solirisrems.com.

Patients may have increased susceptibility to infections, especially
with encapsulated bacteria. Aspergillus infections have occurred in
immunocompromised and neutropenic patients. Children treated with
Soliris may be at increased risk of developing serious infections due to Streptococcus
pneumoniae
and Haemophilus influenza type b (Hib). Soliris
treatment of patients with PNH should not alter anticoagulant management
because the effect of withdrawal of anticoagulant therapy during Soliris
treatment has not been established. Administration of Soliris may result
in infusion reactions, including anaphylaxis or other hypersensitivity
reactions.

In patients with PNH, the most frequently reported adverse events
observed with Soliris treatment in clinical studies were headache,
nasopharyngitis, back pain and nausea. In patients with aHUS, the most
frequently reported adverse events observed with Soliris treatment in
clinical studies were headache, diarrhea, hypertension, upper
respiratory infection, abdominal pain, vomiting, nasopharyngitis,
anemia, cough, peripheral edema, nausea, urinary tract infections, and
pyrexia. In patients with gMG who are anti-AchR antibody-positive, the
most frequently reported adverse reaction observed with Soliris
treatment in the placebo-controlled clinical study (≥10%) was
musculoskeletal pain.

About Alexion

Alexion is a global biopharmaceutical company focused on serving
patients and families affected by rare diseases through the innovation,
development, and commercialization of life-changing therapies. Alexion
is the global leader in complement inhibition and has developed and
commercializes the first and only approved complement inhibitor to treat
patients with paroxysmal nocturnal hemoglobinuria (PNH), atypical
hemolytic uremic syndrome (aHUS), and anti-acetylcholine receptor (AchR)
antibody-positive generalized myasthenia gravis (gMG). In addition,
Alexion has two highly innovative enzyme replacement therapies for
patients with life-threatening and ultra-rare metabolic disorders,
hypophosphatasia (HPP) and lysosomal acid lipase deficiency (LAL-D). As
the leader in complement biology for over 20 years, Alexion focuses its
research efforts on novel molecules and targets in the complement
cascade, and its development efforts on the core therapeutic areas of
hematology, nephrology, neurology, and metabolic disorders. This press
release and further information about Alexion can be found at: www.alexion.com.

[ALXN-G]

Forward-Looking Statement

This press release contains forward-looking statements, including
statements related to the potential medical benefits of ALXN1210 for the
treatment of PNH. Forward-looking statements are subject to factors that
may cause Alexion's results and plans to differ from those expected,
including for example, the risks and uncertainties of drug development,
decisions of regulatory authorities regarding the adequacy of our
research, marketing approval or material limitations on the marketing of
our products, delays, interruptions or failures in the manufacture and
supply of our products and our product candidates, failure to
satisfactorily address matters raised by the FDA and other regulatory
agencies, the possibility that the current rates of adoption of Soliris
in paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic
syndrome (aHUS), or other diseases are not sustained, the possibility
that results of clinical trials are not predictive of safety and
efficacy results of our products in broader patient populations, the
possibility that clinical trials of our product candidates could be
delayed, the adequacy of our pharmacovigilance and drug safety reporting
processes, the risk that third party payers (including governmental
agencies) will not reimburse or continue to reimburse for the use of our
products at acceptable rates or at all, the outcome of challenges and
opposition proceedings to our intellectual property, assertion or
potential assertion by third parties that the manufacture, use or sale
of our products infringes their intellectual property, uncertainties
surrounding legal proceedings, company investigations and government
investigations, including investigations of Alexion by the U.S.
Securities and Exchange Commission (SEC) and U.S. Department of Justice
(DOJ), the risk that anticipated regulatory filings are delayed, the
risk that estimates regarding the number of patients with PNH, aHUS,
gMG, hypophosphatasia (HPP) and lysosomal acid lipase deficiency (LAL-D)
are inaccurate, the risks of changing foreign exchange rates, risks
relating to the potential effects of the Company's restructuring and
relocation of its corporate headquarters, and a variety of other risks
set forth from time to time in Alexion's filings with the SEC, including
but not limited to the risks discussed in Alexion's Quarterly Report on
Form 10-Q for the period ended September 30, 2017 and in our other
filings with the U.S. Securities and Exchange Commission. Alexion does
not intend to update any of these forward-looking statements to reflect
events or circumstances after the date hereof, except when a duty arises
under law.

References

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