New Data Presented at the
"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
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
REGAIN - week 26
extension - week 26
extension - week 52
REGAIN - week 26
extension - week 26
extension - week 52
|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
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
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
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
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
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
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.
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.
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),
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.
Silvestri N, Wolfe G. Treatment-refractory myasthenia gravis.
J. ClinNeuromuscul Dis. 2014;15(4):167-178.
Howard J. Targeting the Complement System in Refractory Myasthenia
Gravis. Supplement to Neurology Reviews.
- Suh J., Goldstein JM, Nowak RJ. Clinical Characteristics of Refractory Myasthenia Gravis Patients. Yale J Biol Med. 2013;86(2):255-260.
Regulation (EU) No 536/2014 of the
European Parliamentand of the Council of 16 April 2014on 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.
- 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.
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.
Sathasivam S. Diagnosis and management of myasthenia gravis. Progress
in Neurology and Psychiatry. January/
- Tüzün E, Huda R, Christadoss P. Complement and cytokine based therapeutic strategies in myasthenia gravis. JAutoimmun. 2011;37(2):136-143.
Meriggioli MN, Sanders DB. Muscle autoantibodies in myasthenia gravis:
beyond diagnosis? Expert
Rev. Clin.Immunol. 2012;8(5), 427-428.
- Conti-Fine, et al. Myasthenia gravis: past, present, and future. J Clin Invest. 2006; 116:2843-2354.
- 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.
- Huda R, Tüzün E, Christadoss P. Targeting complement system to treat myasthenia gravis. Rev. Neurosci. 2014; 25(4): 575-583.
- Meriggioli MN, Sanders DB. Autoimmune myasthenia gravis: emerging clinical and biological heterogeneity. Lancet Neurol. 2009-8(5): 475-490.
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.
Arne Naeveke, PhD, 475-230-3774
Vice President, Investor Relations
Director, Investor Relations
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