Recruitment Under Way in Multinational Phase 3
Trials of ALXN1210 Administered Every Eight Weeks in Patients with
PNH and Atypical Hemolytic Uremic Syndrome (aHUS)
Alexion Pharmaceuticals, Inc. (Nasdaq:ALXN) announced today that
new data from an ongoing Phase 1/2 dose-escalation study of
ALXN1210 in patients with paroxysmal nocturnal hemoglobinuria (PNH)
showed rapid and sustained reductions in lactate dehydrogenase
(LDH), a direct marker of hemolysis (the destruction of red blood
cells), in patients treated with once-monthly dosing. In the
interim analysis of 13 patients, reductions in LDH were observed at
the first evaluable time point (week 1) and were sustained over the
study analysis period of up to 24 weeks. Patients also had
improvements in Functional Assessment of Chronic Illness Therapy
(FACIT)-Fatigue score from baseline, with patients in the
higher-dose cohort achieving a two-fold greater improvement
compared with the lower-dose cohort.1 These findings were presented
in a poster session at the 58th American Society of Hematology
(ASH) annual meeting in San Diego.
ALXN1210 is a highly innovative longer-acting anti-C5 antibody
currently in Phase 3 trials in patients with PNH and atypical
hemolytic uremic syndrome (aHUS). PNH is a debilitating, ultra-rare
blood disorder characterized by complement-mediated hemolysis.2 In
patients with PNH, the combination of LDH ≥1.5 times the upper
limit of normal with any one of the following clinical
symptoms—abdominal pain, chest pain, dyspnea, hemoglobinuria, or
fatigue—is associated with an increased risk of thromboembolism,
the leading cause of death in PNH.3 aHUS is a genetic, chronic,
ultra-rare complement-mediated disease associated with vital organ
failure and premature death.4,5,6
“As the global leader in complement biology, Alexion is
committed to achieving the highest levels of innovation to address
the needs of patients suffering from severe, ultra-rare
complement-mediated disorders like PNH,” said Martin Mackay,
Ph.D., Executive Vice President and Global Head of R&D at
Alexion. “Results from the Phase 1/2 study of ALXN1210 presented at
ASH continue to support earlier findings that this highly
innovative molecule has the potential to offer rapid, complete, and
sustained complement inhibition for patients suffering from the
devastating effects of PNH. We are now focused on enrolling
patients with PNH and aHUS in our Phase 3 registration programs to
evaluate ALXN1210 administered every eight weeks.”
Immediate, Complete, and Sustained Inhibition of C5 with
ALXN1210 Reduces Complement-Mediated Hemolysis in Patients with
Paroxysmal Nocturnal Hemoglobinuria (PNH): Interim Analysis of a
Dose-Escalation Study1
In a poster session, researchers presented interim results from
the Phase 1/2, open-label, 24-week dose-escalating study of
ALXN1210 in patients with PNH. Initial findings from the study were
previously reported at the 21st Congress of the European Hematology
Association (EHA) in June 2016, demonstrating that ALXN1210
achieved rapid and sustained LDH reductions.7 The current analysis
evaluated two cohorts of complement inhibitor-naïve patients with
PNH (ages 18 and older; n=13) who had mean LDH levels ≥3 times the
upper limit of normal. Patients in Cohort 1 (n=6) received either
400 mg or 600 mg induction doses of ALXN1210, followed by a 900 mg
maintenance dose once-monthly for a median of 5.6 months. Patients
in Cohort 2 (n=7) received 600 mg and 900 mg induction doses of
ALXN1210, followed by an 1800 mg maintenance dose once-monthly for
a median of 4.6 months.
All patients showed rapid reductions in mean LDH levels at Week
1 (the first evaluable time point), which were sustained over the
study analysis period. As of the study analysis cutoff, treatment
with ALXN1210 led to a mean reduction in LDH levels of 86 percent
in Cohort 1 (baseline to Week 24) and 85 percent in Cohort 2
(baseline to Week 20). Four out of 6 patients in Cohort 1 (67
percent) and 4 out of 5 patients in Cohort 2 (80 percent) achieved
LDH normalization, and 5 out of 6 patients in Cohort 1 (83 percent)
and 5 out of 5 patients in Cohort 2 (100 percent) achieved mean LDH
levels ≤1.5 times the upper limit of normal. Among five patients
with one or more transfusions in the year prior to the study, one
patient in Cohort 1 required a transfusion, while no patients in
Cohort 2 required a transfusion with ALXN1210 treatment. In
addition, mean levels of hemoglobin, another marker of
intravascular hemolysis, were improved or stable in both
cohorts.
Researchers also presented patient-reported changes in fatigue,
as measured by the FACIT-Fatigue Scale. From baseline to Week 24,
mean FACIT-Fatigue score improved from 35.5 to 41.8 points (28.7
percent) for Cohort 1 and from 25.4 to 40.8 points (76.2 percent)
for Cohort 2.
“In this interim analysis, ALXN1210 was associated with rapid
and sustained reductions in LDH levels for up to six months in
patients with PNH. Notably, patients in the higher-dose cohort had
a 2-fold greater improvement in FACIT-Fatigue score, as well as no
evidence of hemolysis or need for transfusion,” said lead author
Jong-Wook Lee, M.D., Ph.D., Professor, Division of Hematology,
Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul,
Korea. “These findings are consistent with a better hemolytic
response with the higher 1800 mg once-monthly dose and suggest that
the 900 mg once-monthly dose may be inadequate in comparison with
1800 mg for complete suppression of complement-mediated
hemolysis.”
No serious adverse events or study withdrawals were observed in
either patient cohort. The most common treatment-related adverse
event was headache, which occurred in four of 13 patients (30.8
percent) and resolved during ongoing treatment with ALXN1210.
About ALXN1210
ALXN1210 is a highly innovative, longer-acting anti-C5 antibody
discovered and developed by Alexion that inhibits terminal
complement. In early studies, ALXN1210 demonstrated rapid,
complete, and sustained reduction of free C5 levels.8 Alexion has
completed enrollment in two ongoing clinical studies of ALXN1210 in
patients with PNH—a Phase 1/2 dose-escalating study and an
open-label, multi-dose Phase 2 study that is also evaluating longer
dosing intervals beyond 8 weeks.
ALXN1210 is currently in Phase 3 trials in patients with PNH and
aHUS. In addition, Alexion is conducting a Phase 1 study to
evaluate a new formulation of ALXN1210 administered subcutaneously
in healthy volunteers.
In June 2016, the European Commission granted Orphan Drug
Designation (ODD) to ALXN1210 for the treatment of patients with
PNH.
About Paroxysmal Nocturnal Hemoglobinuria (PNH)
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 30s.2 Approximately 10 percent of all
patients first develop symptoms at 21 years of age or younger.9 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.10 In
the period of time before treatment was available, it had been
estimated that approximately one-third of patients with PNH did not
survive more than 5 years from the time of diagnosis.11 PNH
has been identified more commonly among patients with disorders of
the bone marrow, including aplastic anemia (AA) and myelodysplastic
syndromes (MDS).12-14 In patients with thrombosis of unknown
origin, PNH may be an underlying cause.15
About Atypical Hemolytic Uremic Syndrome (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.4,5 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.4,6
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).16
Moreover, 33-40 percent of patients die or progress to end-stage
renal disease with the first clinical manifestation of aHUS despite
PE/PI.17,18 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.17
aHUS affects both children and adults. Complement-mediated 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 40-50 percent of patients with a
confirmed diagnosis of aHUS.16,17,19
About Alexion
Alexion is a global biopharmaceutical company focused on
developing and delivering life-transforming therapies for patients
with devastating and rare disorders. 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) and atypical hemolytic
uremic syndrome (aHUS), two life-threatening ultra-rare disorders.
In addition, Alexion’s metabolic franchise includes two highly
innovative enzyme replacement therapies for patients with
life-threatening and ultra-rare disorders, hypophosphatasia (HPP)
and lysosomal acid lipase deficiency (LAL-D). Alexion is advancing
the most robust rare disease pipeline in the biotech industry with
highly innovative product candidates in multiple therapeutic areas.
This press release and further information about Alexion can be
found at: www.alexion.com.
[ALXN-G]
Forward-Looking Statements
This press release contains forward-looking statements,
including statements related to Alexion's development plans for
ALXN1210, the medical benefits of ALXN1210 for the treatment of PNH
and aHUS, medical and commercial potential of ALXN1210, and plans
for regulatory filings for ALXN1210. Forward-looking statements are
subject to factors that may cause Alexion's results and plans to
materially differ from those expected, including for example,
decisions of regulatory authorities regarding 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, progress in establishing and
developing commercial infrastructure, failure to satisfactorily
address matters raised by the FDA and other regulatory agencies,
the possibility that results of clinical trials are not predictive
of safety and efficacy results of our products in broader patient
populations in the disease studied or other diseases, the risk that
strategic transactions will not result in short-term or long-term
benefits, the possibility that current results of commercialization
are not predictive of future rates of adoption of Soliris in PNH,
aHUS or other diseases, the possibility that clinical trials of our
product candidates could be delayed or that additional research and
testing is required by regulatory agencies, including for ALXN1210,
the adequacy of our pharmacovigilance and drug safety reporting
processes, the risk that third party payors (including governmental
agencies) will not reimburse or continue to reimburse for the use
of our products at acceptable rates or at all, risks regarding
government investigations, including investigations of Alexion by
the SEC and DOJ, risks relating to the internal investigation being
conducted by the Audit and Finance Committee, the risk that
anticipated regulatory filings are delayed, including for ALXN1210,
the risk that estimates regarding the number of patients with PNH,
aHUS, HPP and LAL-D are inaccurate, the risks of shifting foreign
exchange rates, and a variety of other risks set forth from time to
time in Alexion's filings with the U.S. Securities and Exchange
Commission, including but not limited to the risks discussed in
Alexion's Quarterly Report on Form 10-Q for the period ended June
30, 2016 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
1. Lee JW, Bachman ES, Aguzzi R, et al.
Immediate, complete, and sustained inhibition of C5 with ALXN1210
reduces complement-mediated hemolysis in patients with paroxysmal
nocturnal hemoglobinuria (PNH): interim analysis of a
dose-escalation study (Abstract 2428). Poster presented at the 58th
annual meeting of the American Society of Hematology (ASH), San
Diego, California, December 3-6, 2016. 2. Socié G, Mary JY, de
Gramont A, et al. Paroxysmal nocturnal haemoglobinuria: long-term
follow-up and prognostic factors. Lancet. 1996: 348:573-577. 3.
Lee JW, Jang JH, Kim JS, et al.
Clinical signs and symptoms associated with increased risk for
thrombosis in patients with paroxysmal nocturnal hemoglobinuria
from a Korean Registry. Int J Hematol. 2013
Jun;97(6):749-57.
4. Benz K, Amann K. Thrombotic microangiopathy: new insights. Curr
Opin Nephrol Hypertens. 2010;19(3):242-247. 5. Ariceta G, Besbas N,
Johnson S, et al. Guideline for the investigation and initial
therapy of diarrhea-negative hemolytic uremic syndrome. Pediatr
Nephrol. 2009;24:687-696. 6. Tsai HM. The molecular biology of
thrombotic microangiopathy. Kidney Int. 2006;70(1):16-23. 7. Lee
JW, Bachman E, Aguzzi R, et al. ALXN1210, a long-acting C5
inhibitor, results in rapid and sustained reduction of LDH with a
monthly dosing interval in patients with PNH: preliminary data from
a dose-escalation study (Abstract 4126). Poster presented at 21st
Congress of the European Hematology Association (EHA), Copenhagen,
Denmark, June 9-12, 2016. Abstract 4126. 8. Sahelijo L, Mujeebuddin
A, Mitchell D, et al. First in human single-ascending dose study:
safety, biomarker, pharmacokinetics and exposure-response
relationships of ALXN1210, a humanized monoclonal antibody to C5,
with marked half-life extension and potential for significantly
longer dosing intervals. Blood. 2015;126 (23):4777. 9. Parker C,
Omine M, Richards S, et al. Diagnosis and management of paroxysmal
nocturnal hemoglobinuria. Blood. 2005;106(12):3699-3709. 10. Dacie
JV, Lewis SM. Paroxysmal nocturnal haemoglobinuria: clinical
manifestations, haematology, and nature of the disease. Ser Haemat.
1972;5:3-23. 11. Hillmen P, Lewis SM, Bessler M, Luzzatto L, Dacie
JV. Natural history of paroxysmal nocturnal hemoglobinuria. N Engl
J Med. 1995;333(19):1253-1258. 12. Wang H, Chuhjo T, Yasue S, Omine
M, Naka S. Clinical Significance of a minor population of
paroxysmal nocturnal hemoglobinuria-type cells in bone marrow
failure syndrome. Blood. 2002;100(12):3897-3902. 13. Iwanga M,
Furukawa K, Amenomori T, et al. Paroxysmal nocturnal hemoglobinuria
clones in patients with myelodysplastic syndromes. Br J Haematol.
1998;102(2):465-474. 14. Maciejewski JP, Rivera C, Kook H, Dunn D,
Young NS. Relationship between bone marrow failure syndromes and
the presence of glycophosphatidyl inositol-anchored
protein-deficient clones. Br J Haematol. 2001;115:1015-1022. 15.
Hill A, Kelly RJ, Hillmen P. Thrombosis in paroxysmal nocturnal
hemoglobinuria. Blood. 2013;121:4985-4996. 16. Fremeaux-Bacchi, et
al. Genetics and Outcome of Atypical Hemolytic Uremic Syndrome: A
Nationwide French Series Comparing Children and Adults. Clin J Am
Soc Nephrol. 2013 Apr 5; 8(4): 554–562. 17. Noris M, Caprioli J,
Bresin E, et al. Relative Role of genetic complement abnormalities
in sporadic and familial aHUS and their impact on clinical
phenotype. Clin J Am Soc Nephrol. 2010;5:1844-59. 18. Caprioli J,
Noris M, Brioschi S, et al; for the International Registry of
Recurrent and Familial HUS/TTP. Genetics of HUS: the impact of MCP,
CFH, and IF mutations on clinical presentation, response to
treatment, and outcome. Blood. 2006;108:1267-1279. 19. Bresin E, et
al. Combined Complement Gene Mutations in Atypical Hemolytic Uremic
Syndrome Influence Clinical Phenotype. J Am Soc Nephrol. 2013;24:
475-486.
View source
version on businesswire.com: http://www.businesswire.com/news/home/20161204005031/en/
Alexion Pharmaceuticals, Inc.MediaStephanie Fagan,
475-230-3777Senior Vice President, Corporate CommunicationsorKim
Diamond, 475-230-3775Executive Director, Corporate
CommunicationsORInvestorsElena Ridloff, CFA, 475-230-3601Vice
President, Investor Relations
Alexion Pharmaceuticals (NASDAQ:ALXN)
Historical Stock Chart
From Mar 2024 to Apr 2024
Alexion Pharmaceuticals (NASDAQ:ALXN)
Historical Stock Chart
From Apr 2023 to Apr 2024