Interim Analysis from Phase 3 Open-Label Extension Study Shows Sustained Benefits of Soliris® (Eculizumab) Treatment for Patients with Refractory Generalized Myasthenia Gravis

New Data Presented at the American Association of Neuromuscular &
Electrodiagnostic Medicine Annual Meeting Further Substantiate and
Extend Results from Pivotal REGAIN Study

NEW HAVEN, Conn.–(BUSINESS WIRE)–Alexion Pharmaceuticals, Inc. (NASDAQ:ALXN) announced today results from
an interim analysis of an ongoing Phase 3 open-label extension study of
the pivotal, placebo-controlled REGAIN study of Soliris® (eculizumab)
for the treatment of patients with refractory generalized myasthenia
gravis (gMG) who are anti-acetylcholine receptor (AChR)
antibody-positive. The new results show sustained treatment benefits
across a range of MG-specific assessment scales through an additional 52
weeks for patients who continued to receive Soliris, and also
demonstrate rapid, significant and sustained improvements through 52
weeks for patients who had crossed over from placebo in REGAIN to
Soliris treatment in the extension study. The safety profile of Soliris
was consistent with that observed in the REGAIN study. The results are
presented at the annual meeting of the American Association of
Neuromuscular & Electrodiagnostic Medicine (AANEM) in Phoenix, Arizona.

“There is an urgent need for a treatment for patients with refractory
gMG who have attempted multiple therapies and continue to suffer from
severe symptoms and complications,” said Professor James F. Howard, MD,
Department of Neurology at the University of North Carolina, Chapel
Hill, USA, and lead investigator in REGAIN and its open-label extension
study. “These new results build on the findings of the REGAIN study, and
it is encouraging to see the rapid and sustained benefits of Soliris
treatment with patients recovering functional ability to carry out
activities of daily living, and quality of life.”

Results presented show that the benefits for patients treated with
Soliris in REGAIN through 26 weeks were maintained in the extension
study across all four assessment scales for an additional 52 weeks (78
weeks in total). For patients who received placebo in REGAIN and then
were treated with Soliris in the extension study, significant treatment
benefits occurred within 1 to 4 weeks and were sustained through 52
weeks across all four assessment scales.1

Treatment benefits in the REGAIN open-label extension study1

                                               
Assessment scale         Soliris         Soliris/Soliris         Soliris/Soliris         Placebo         Placebo/Soliris         Placebo/Soliris

REGAIN – week 26

n=55-56

       

extension – week 26

n=47-49

       

extension – week 52

n=20

       

REGAIN – week 26

n=59

       

extension – week 26

n=55-56

       

extension – week 52

n=20

MG-ADL -4.4       [-5.6, -3.3] -5.2       [-6.3, -4.2] -4.4       [-6.0, -2.7] -2.3       [-3.2, -1.5] -4.9       [-5.8, -4.0] -5.3       [-6.8 -3.7]
QMG -5.0 [-6.4, -3.6] -5.2 [-6.7, -3.6] -4.5 [-6.7, -2.3] -1.7 [-2.7, -0.6] -4.8 [-6.4, -3.3] -6.4 [-8.8 -4.0]
MGC -8.4 [-10.7, -6.2] -10.0 [-12.3, -7.8] -8.8 [-11.9, -5.6] -5.0 [-6.8, -3.2] -10.0 [-12.0, -8.0] -10.0 [-13.3,-6.7]
MG-QoL 15 -12.8 [-16.6, -9.0] -15.2 [-19.0, -11.3] -14.9 [-21.7, -8.1] -5.4 [-7.8, -2.9] -12.9 [-16.6, -9.1] -16.2 [-21.3,-11.1]
 

Treatment effects measured in decreased mean scores (using repeated
measures from baseline) at given time points compared to baseline at
enrollment in the REGAIN study (summarized for patients who enrolled in
the extension study) [95% confidence intervals]

MG-ADL – MG-Activities of Daily Living, a patient-reported assessment of
functional ability to carry out daily activities
QMG – Quantitative
MG, a clinical assessment of muscle strength by physicians
MGC – MG
Composite, a patient- and physician-reported assessment of functional
ability and signs and symptoms of MG
MG-QoL 15 – MG Quality of Life
15, a patient-reported assessment of MG-specific quality of life

“We are grateful to the patients and investigators who continue to
participate in this ongoing extension study that further substantiates
the rapid and sustained benefits of complement inhibition for this
debilitating, chronic and progressive neurological disorder,” said John
Orloff, M.D., Executive Vice President and Head of Research &
Development at Alexion.

Patients with refractory gMG represent an ultra-rare subset of patients2-5
who have difficulties walking, talking, swallowing and breathing
normally despite multiple therapies for MG. Exacerbations and crises of
their disease may require hospitalization and intensive care and may be
life-threatening.6-8 Chronic uncontrolled activation of the
complement cascade, a part of the immune system, can play a major role
in the debilitating symptoms and potentially life-threatening
complications of the disease.9-11

Soliris is the first and only complement inhibitor, and the only
complement-based therapy approved in the European Union (EU) for the
treatment of patients with refractory gMG who are anti-AChR
antibody-positive. Alexion’s supplemental Biologics License Application
(sBLA) in the U.S. and a supplemental new drug application in Japan for
Soliris for similar indications have been accepted for review by the
U.S. Food and Drug Administration (FDA) and the Japanese Ministry of
Health, Labour and Welfare (MHLW), respectively. Soliris has received
Orphan Drug Designation (ODD) for the treatment of patients with MG in
the U.S. and EU, and for the treatment of patients with refractory gMG
in Japan.

About the Open-Label Extension Study (MG-302)

94% (117/125) of patients who completed the REGAIN study enrolled in the
open-label extension, of which 56 continued to receive Soliris
(Soliris/Soliris group) and 61 were switched from placebo to Soliris
(placebo/Soliris group) within two weeks of completing the REGAIN study.
Patients were not informed of prior treatment assignment in REGAIN
through a four-week blinded induction phase, after which all patients
received ongoing open-label treatment with Soliris (1,200 mg/dose) every
two weeks. For this interim analysis, 49 patients in the Soliris/Soliris
group and 56 patients in the placebo/Soliris group completed week 26
assessments; 20 patients in each group completed week 52 assessments.
Patient numbers for scores at week 26 may differ slightly because a
total score could not be computed when an assessment was missed or data
were not complete. Mean scores over time were calculated using repeated
measures from baseline. The study is ongoing and planned to continue
until January 2019.

About REGAIN (MG-301)

This was a randomized, double-blind, placebo-controlled, multicenter
Phase 3 clinical study that evaluated the efficacy and safety of Soliris
over 26 weeks in 125 patients with refractory gMG who had a confirmed
diagnosis of MG with positive serologic test for antibodies against
AChR. Patients initially received 900 mg of Soliris or placebo weekly
for 4 weeks followed by 1,200 mg of Soliris or placebo 1 week later, and
then 1,200 mg of Soliris or placebo every 2 weeks. The primary efficacy
endpoint of change from baseline in MG-ADL total score at week 26, as
well as the three secondary endpoints —changes from baseline in QMG,
MGC, and MG-QoL 15—were assessed using a worst-rank analysis. The study
narrowly missed statistical significance on the primary endpoint
(p=0.0698). However, 18 out of 22 pre-specified endpoints and analyses
showed results with p-values <0.05 across the four assessment scales, supporting early, sustained and substantial responses. The safety profile was consistent with what has been reported for Soliris during the past 10 years in patients with paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS).

The REGAIN study (MG-301) and its open-label extension study (MG-302)
are sponsored by Alexion.

About Refractory Generalized Myasthenia Gravis

Patients with refractory generalized myasthenia gravis (gMG) who are
anti-acetylcholine receptor (AChR) antibody-positive represent an
ultra-rare subset of MG patients2-4 who continue to suffer
from severe disease symptoms and complications despite therapies
currently used for MG.2,3,12

MG is a debilitating, chronic and progressive autoimmune neuromuscular
disease that can occur at any age but most commonly begins for women
before the age of 40 and men after the age of 60.6,7,13,14 It
typically begins with weakness in the muscles that control the movements
of the eyes and eyelids, and often progresses to the more severe and
generalized form, known as gMG with weakness of the head, neck, trunk,
limb and respiratory muscles.14

While most patients with gMG can be managed with therapies for MG, 10%
to 15% of patients are considered refractory—meaning they fail to
respond adequately to or cannot tolerate multiple therapies for MG and
continue to suffer profound muscle weakness, and severe disease symptoms
that limit function.2,4,12 Patients with refractory gMG can
suffer from slurred speech; choking; impaired swallowing; double or
blurred vision; disabling fatigue; immobility requiring assistance;
shortness of breath, and episodes of respiratory failure. Complications,
exacerbations and myasthenic crises can require hospital and intensive
care unit admissions with prolonged stays and can be life-threatening.6-8

In patients with anti-AChR antibody-positive MG, the body’s own immune
system turns on itself to produce antibodies against AChR, a receptor
located on muscle cells in the neuromuscular junction (NMJ) and used by
nerve cells to communicate with the muscles these nerves control.6,7
The binding of these antibodies to AChR activates the complement
cascade, another part of the immune system, which leads to a localized
destruction of the muscle membrane at the NMJ. As a result, the
communication between nerve and muscle is impaired, which in turn leads
to a loss of normal muscle function.9-11,15

About Soliris® (eculizumab)

Soliris® is a first-in-class complement inhibitor that works
by inhibiting the terminal part of the complement cascade, a part of the
immune system that, when activated in an uncontrolled manner, plays a
role in serious ultra-rare disorders like paroxysmal nocturnal
hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS) and
anti-acetylcholine receptor (AChR) antibody-positive refractory
generalized myasthenia gravis (gMG).

Soliris is approved in the U.S., EU, Japan and other countries as the
first and only treatment for patients with PNH and aHUS, and in the EU
as the first and only treatment for refractory gMG in patients who are
anti-AChR antibody-positive. Soliris is not indicated for the treatment
of patients with Shiga-toxin E. coli-related hemolytic uremic syndrome
(STEC-HUS). 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.

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), atypical hemolytic uremic syndrome (aHUS), and
refractory 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 news release contains forward-looking statements, including
statements related to the potential medical benefits of Soliris®
(eculizumab) for the treatment of generalized myasthenia gravis (gMG),
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, 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 eculizumab for the treatment
of gMG, 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 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, risks regarding
government investigations, including investigations of Alexion by the
SEC and DOJ, the risk that anticipated regulatory filings are delayed,
the risk that estimates regarding the number of patients with gMG are
inaccurate, 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, 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

  1. Howard JF, Wang JJ, O’Brien F, Mantegazza R and the REGAIN study
    group. Efficacy of eculizumab is maintained beyond 26 weeks in
    patients with AChR+ refractory generalized myasthenia gravis (gMG).
    Poster (abstract 211), annual meeting of the American Association of
    Neuromuscular & Electrodiagnostic Medicine (AANEM), September 14, 2017.
  2. Silvestri N, Wolfe G. Treatment-refractory myasthenia gravis. J. Clin
    Neuromuscul Dis. 2014;15(4):167-178.
  3. Howard J. Targeting the Complement System in Refractory Myasthenia
    Gravis. Supplement to Neurology Reviews. February 2016.
  4. Suh J., Goldstein JM, Nowak RJ. Clinical Characteristics of Refractory
    Myasthenia Gravis Patients. Yale J Biol Med. 2013;86(2):255-260.
  5. Regulation (EU) No 536/2014 of the European Parliament and of the
    Council of 16 April 2014 on clinical trials on medicinal products for
    human use, and repealing Directive 2001/20/EC. http://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32000R0141&qid=1421232987002&from=EN.
    Accessed on June 26, 2017.
  6. Howard JF, Barohn RJ, Cutter GR et al. A randomized, double-blind,
    placebo-controlled phase II study of eculizumab in patients with
    refractory generalized myasthenia gravis. Muscle Nerve.
    2013;48(1):76-84.
  7. National Institute of Neurological Disorders and Stroke. Myasthenia
    Gravis Fact Sheet. Publication date May 2017. http://www.ninds.nih.gov/disorders/myasthenia_gravis/detail_myasthenia_gravis.htm.
  8. Sathasivam S. Diagnosis and management of myasthenia gravis. Progress
    in Neurology and Psychiatry. January/February 2014.
  9. Tüzün E, Huda R, Christadoss P. Complement and cytokine based
    therapeutic strategies in myasthenia gravis. JAutoimmun.
    2011;37(2):136-143.
  10. Meriggioli MN, Sanders DB. Muscle autoantibodies in myasthenia gravis:
    beyond diagnosis? Expert Rev. Clin.Immunol. 2012;8(5), 427-428.
  11. Conti-Fine, et al. Myasthenia gravis: past, present, and future. J
    Clin Invest. 2006; 116:2843-2354.
  12. Sanders DB, Wolfe, GI, Benatar M, et al. International consensus
    guidance for management of myasthenia gravis: Executive summary.
    Neurology. 2016 Jul 26;87(4):419-25.
  13. Huda R, Tüzün E, Christadoss P. Targeting complement system to treat
    myasthenia gravis. Rev. Neurosci. 2014; 25(4): 575–583.
  14. Meriggioli MN, Sanders DB. Autoimmune myasthenia gravis: emerging
    clinical and biological heterogeneity. Lancet Neurol. 2009-8(5):
    475-490.
  15. Buzzard, K. A., N. J. Meyer, T. A. Hardy, D. S. Riminton and S. W.
    Reddel. Induction intravenous cyclophosphamide followed by maintenance
    oral immunosuppression in refractory myasthenia gravis. Muscle Nerve.
    2015;52(2): 204-210.

Contacts

Alexion Pharmaceuticals, Inc.
Media
Arne Naeveke, PhD,
475-230-3774
Executive Director, Product Communications
or
Investors
Elena
Ridloff, CFA, 475-230-3601
Vice President, Investor Relations
or
Catherine
Hu, 475-230-3599
Director, Investor Relations