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NEW HAVEN, Conn.–(BUSINESS WIRE)–Alexion Pharmaceuticals, Inc. (NASDAQ: ALXN) today announced topline results from the REGAIN study, a Phase 3 registration trial of eculizumab (Soliris®) in patients with refractory generalized myasthenia gravis (gMG). Refractory gMG is an ultra-rare segment of MG—a debilitating, complement-mediated neuromuscular disease—in which patients have largely exhausted conventional therapy and continue to suffer …

NEW HAVEN, Conn.–(BUSINESS WIRE)–Alexion Pharmaceuticals, Inc. (NASDAQ: ALXN) today announced topline
results from the REGAIN study, a Phase 3 registration trial of
eculizumab (Soliris®) in patients with refractory generalized
myasthenia gravis (gMG). Refractory gMG is an ultra-rare segment of MG—a
debilitating, complement-mediated neuromuscular disease—in which
patients have largely exhausted conventional therapy and continue to
suffer profound muscle weakness throughout the body, resulting in
slurred speech, impaired swallowing and choking, double vision, upper
and lower extremity weakness, disabling fatigue, shortness of breath due
to respiratory muscle weakness, and episodes of respiratory failure.1-5
In the study, the primary efficacy endpoint of change from baseline in
Myasthenia Gravis-Activities of Daily Living Profile (MG-ADL) total
score, a patient-reported assessment, at week 26, did not reach
statistical significance (p=0.0698) as measured by a worst-rank analysis.
The first prospectively defined secondary efficacy endpoint of change
from baseline in Quantitative Myasthenia Gravis (QMG) total score, a
physician-administered assessment of MG clinical severity, with
eculizumab treatment compared to placebo at week 26, achieved a p-value
of 0.0129 as measured by a worst-rank analysis. In addition, the second
and third prospectively defined secondary efficacy endpoints of
responder status in MG-ADL and QMG achieved p-values <0.05: the
proportion of patients with at least a 3-point reduction in MG-ADL total
score and no rescue therapy from baseline to week 26 with eculizumab
treatment compared to placebo achieved a p-value of 0.0229, and the
proportion of patients with at least a 5-point reduction in QMG total
score and no rescue therapy from baseline to week 26 with eculizumab
treatment compared to placebo achieved a p-value of 0.0018.
“While the REGAIN study missed its primary endpoint, I am encouraged by
the clinically meaningful improvements in MG-ADL and QMG measures in
patients treated with eculizumab compared with placebo. The magnitude of
effect on QMG observed in this large, prospective registration trial is
unprecedented in my more than 30 years of clinical investigation of
refractory MG patients, and I look forward to presenting additional
outcomes at ICNMD,” said James F. Howard Jr., M.D., Distinguished
Professor of Neuromuscular Disease, Professor of Neurology, Medicine &
Allied Health, and Chief, Neuromuscular Disorders Section, The
University of North Carolina School of Medicine. “There is an urgent
need in the MG community for a therapy with the potential to
dramatically improve the lives of patients with refractory MG, who
continue to experience profound complement-mediated muscle weakness that
makes it difficult or impossible to perform simple daily activities,
including walking, talking, swallowing, and even breathing normally.”
Pre-specified sensitivity analyses were prospectively defined to
validate results for the primary and first secondary endpoints. Three of
the four prospectively defined sensitivity analyses around the primary
endpoint of MG-ADL achieved p-values <0.05, including the sensitivity
analysis for change from baseline in MG-ADL using repeated measures,
which showed a mean change with eculizumab treatment at week 26 of -4.2
versus a mean change with placebo at week 26 of -2.3 and achieved a
p-value of 0.0058. Additionally, all four prospectively defined
sensitivity analyses around the first secondary endpoint of QMG achieved
p-values <0.05, including the sensitivity analysis for change from
baseline in QMG using repeated measures, which showed a mean change with
eculizumab treatment at week 26 of -4.6 versus a mean change with
placebo at week 26 of -1.6 and achieved a p-value of 0.0006.
“The primary endpoint of the REGAIN study missed statistical
significance, however the findings from this study underscore the
pivotal role of complement inhibition in addressing the underlying
pathophysiology of refractory gMG. Importantly, the totality of data
reviewed to date, including the first three secondary endpoints and a
series of prospectively defined sensitivity analyses, shows early and
sustained substantial improvements over 26 weeks for patients treated
with eculizumab compared to placebo,” said Martin Mackay, Ph.D.,
Executive Vice President and Global Head of R&D at Alexion. “Today,
patients with refractory gMG continue to suffer severe disease-related
morbidities that often lead to hospital visits and ICU stays, despite
currently available therapies. We look forward to discussing the results
with regulators in the U.S. and Europe, and working together to address
the urgent needs of patients with this devastating disease.”
Alexion continues to analyze the data from the REGAIN study, and results
will be presented on July 7, 2016, during the Hot Topics session at the
14th International Congress on Neuromuscular Diseases (ICNMD) in Toronto.
The safety of eculizumab in this study was consistent with the Soliris
labels. The most common adverse events in patients receiving eculizumab
and placebo, respectively, were: headache (16.1%, 19.0%), upper
respiratory tract infection (16.1%, 19.0%), nasopharyngitis (14.5%,
15.9%), myasthenia gravis (9.7%, 17.5%), and nausea (12.9%, 14.3%).
Serious adverse events were reported in 14.5% of eculizumab patients and
28.6% of placebo patients. Four patients receiving eculizumab (6.5%)
discontinued treatment due to an adverse event. There were no
discontinuations due to adverse events in the placebo arm.
Ninety-four percent of patients (117 of 125) from the REGAIN study
continued into a Phase 3 open-label extension study evaluating the
safety and efficacy of eculizumab in the treatment of patients with
refractory gMG. Eculizumab has received Orphan Drug Designation (ODD)
for the treatment of patients with MG in the U.S., EU, and Japan.
Eculizumab is not approved in any country for the treatment of patients
with gMG.
REGAIN Study Design
The REGAIN study is a randomized, double-blind, placebo-controlled,
multicenter trial evaluating the safety and efficacy of eculizumab in
patients with refractory gMG. The study enrolled and treated 125 adult
patients across North America, South America, Europe, and Asia. Patients
had a confirmed MG diagnosis with positive serologic test for anti-AChR
antibodies. All patients were required to have previously failed
treatment with at least two immunosuppressive agents or failed treatment
with at least one immunosuppressive agent and required chronic plasma
exchange or IVIg, and had an MG-ADL total score ≥6 at study entry.
Patients were randomized 1:1 to receive eculizumab or placebo for a
total of 26 weeks. Patients initially received 900 mg of eculizumab or
placebo weekly for 4 weeks followed by 1200 mg of eculizumab or placebo
one week later, and then 1200 mg of eculizumab or placebo every two
weeks. Patients were able to continue to receive stable dose and type of
supportive immunosuppressive therapy (IST), but no new ISTs and no
increase in IST dosage were permitted during the trial, unless patient
required rescue therapy for disease worsening.
The primary efficacy endpoint of change from baseline in MG-ADL total
score at week 26 and the first secondary endpoint of change from
baseline in QMG total score at week 26 were assessed using a worst-rank
score analysis.
Conference Call
Alexion will host a conference call/webcast today, June 6, at 5:00 p.m.
to discuss the data. To participate in this call, dial (844) 309-0617
(USA) or (661) 378-9464 (international), confirmation code 20710881,
shortly before 5:00 p.m. A replay of the call will be available for a
limited period following the call, beginning at 8:00 p.m. The replay
number is (855) 859-2056 (USA) or (404) 537-3406 (international),
confirmation code 20710881. The audio webcast can be found on the
Investor page of Alexion’s website at: http://ir.alexionpharm.com.
About Refractory Generalized Myasthenia Gravis
Refractory generalized myasthenia gravis (gMG) is an ultra-rare segment
of MG—a debilitating, complement-mediated neuromuscular disease—in which
patients experience severe morbidities despite currently available MG
therapies.1,2,3
MG typically begins with weakness in the ocular muscles and often
progresses to the more severe and generalized form, known as gMG, to
include weakness of the head, neck, trunk, limb and respiratory muscles.6
While most gMG patients are managed with conventional therapies, 10% to
15% of patients are considered refractory—meaning they have largely
exhausted conventional therapy and continue to suffer profound muscle
weakness throughout the body, resulting in slurred speech, impaired
swallowing and choking, double vision, upper and lower extremity
weakness, disabling fatigue, shortness of breath due to respiratory
muscle weakness, and episodes of respiratory failure.4,5,7 Patients
with refractory gMG frequently require hospitalization, often involving
intensive care unit stays.8
Today, there are no therapies that are effective in this ultra-rare
population of patients suffering from refractory gMG.
About Soliris® (eculizumab)
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 U.S. (2007), European Union (2007),
Japan (2010) and other countries as the first and only treatment for
patients with paroxysmal nocturnal hemoglobinuria (PNH) to reduce
hemolysis. PNH is a debilitating, ultra-rare and life-threatening blood
disorder, characterized by complement-mediated hemolysis (destruction of
red blood cells). Soliris is also approved in the U.S. (2011), European
Union (2011), Japan (2013) and other countries as the first and only
treatment for patients with atypical hemolytic uremic syndrome (aHUS) to
inhibit complement-mediated thrombotic microangiopathy, or TMA (blood
clots in small vessels). aHUS is a debilitating, ultra-rare and
life-threatening genetic disorder characterized by complement-mediated
TMA. Soliris is not indicated for the treatment of patients with
Shiga-toxin E. coli-related hemolytic uremic syndrome
(STEC-HUS). For the breakthrough medical innovation in complement
inhibition, Alexion and Soliris have received some of the pharmaceutical
industry’s highest honors: the Prix Galien USA (2008, Best Biotechnology
Product) and France (2009, Rare Disease Treatment).
More information, including the full U.S. prescribing information, on
Soliris is available at www.soliris.net.
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 news release contains forward-looking statements, including
statements related to the potential medical benefits and commercial
potential of Soliris for the treatment of myasthenia gravis, and
Alexion’s future clinical, regulatory and commercial plans for Soliris
for the treatment of myasthenia gravis. Forward-looking statements are
subject to factors that may cause Alexion’s results and plans to 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
possibility that clinical trials of our product candidates could be
delayed or that additional research and testing is required by
regulatory agencies, 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 the SEC and DOJ investigations, the
risk that estimates regarding the number of patients with the diseases
that our products treat 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 March 31, 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.Suh J, Goldstein JM, Nowak RJ. Clinical characteristics of
refractory myasthenia gravis patients. Yale J Biol Med 2013; 86:
255–60.
2.Gilhus NE, Verschuuren JJ. Myasthenia gravis: subgroup
classification and therapeutic strategies. Lancet Neurol 2015; 14:
1023–36.
3.Drachman D, Adams R, Hu R, Jones R, Brodsky R. Rebooting the Immune
System with High-Dose Cyclophosphamide for Treatment of Refractory
Myasthenia Gravis. Ann. N.Y. Acad. Sci. 2008;1132:305–314.
4.Sathasivam S. Diagnosis and management of myasthenia gravis.
Progress in Neurology and Psychiatry January/February 2014.
5.Howard JF. Myasthenia gravis: A manual for the health care provider.
Myasthenia Gravis Foundation of America, Inc. 2008.
6.Melzer N, Ruck T, FuhrP, Gold R, Hohlfeld R, Marx A, Melms A,
Tackenberg B, Schalke B, Schneider-Gold C, Zimprich F, Meuth S,
Wiendl H. Clinical features, Pathogenesis, and Treatment of
Myasthenia Gravis: a supplement to the Guidelines of the German
Neurological Society. J Neurol online: 17 February 2016.
7.Targeting the Complement System in Refractory Myasthenia Gravis.
Supplement to Neurology Reviews. February 2016.
8.Safety and efficacy of eculizumab in refractory generalized
myasthenia gravis (REGAIN study). Clinicaltrials.gov identifier
NCT01997229.

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