-- Soliris® Reduced the Risk of Adjudicated On-Trial Relapse by 94.2% Compared to Placebo (p < 0.0001) --
-- Safety Profile Consistent with that Seen in Previous Studies and Real-World Use --
-- Preparing for Regulatory Submissions in the US,
-- Conference Call/Webcast Scheduled for Today,
The study met its primary endpoint of time to first adjudicated on-trial relapse, demonstrating that treatment with Soliris® reduced the risk of NMOSD relapse by 94.2 percent compared to placebo (p < 0.0001). At 48 weeks, 97.9 percent of patients receiving Soliris® were free of relapse compared to 63.2 percent of patients receiving placebo. Soliris® was generally well tolerated with a safety profile consistent with that seen in previous clinical studies and real-world use in its three approved indications. No cases of meningococcal infection were observed.
“These results far exceeded our expectations. The remarkable reduction
in relapse risk demonstrates the unique ability of Soliris®
to inhibit complement, and suggests a promising new treatment for
“The primary goal in treating NMOSD is relapse prevention as each
relapse further increases disability, which makes this disease so
devastating. For decades, we have been hoping for a therapy that can
prevent relapse and subsequent accumulation of disability by addressing
a critical underlying cause of the disease,” said
Detailed results from this Phase 3 study will be presented at a future medical congress.
NMOSD is a rare, devastating, complement-mediated disorder of the central nervous system (CNS). Patients experience an unpredictable, relapsing, and deteriorating course of disease with each relapse adding to the disability, and potentially leading to premature death. Optic neuritis can cause eye pain and blindness. Transverse myelitis can cause severe weakness, impaired mobility, sensory and motor disability, loss of bowel and bladder function, paralysis, and respiratory failure.3,8,9 Significant proportions of patients sustain permanent severe disability, including blindness and paralysis, or die within six years (75 months) of disease onset. Specifically, one third (34 percent) of patients sustain permanent motor disability, almost one quarter (23 percent) become wheelchair-dependent, almost one fifth (18 percent) suffer from permanent visual disability, and almost one in 10 (9 percent) die.10
Patients with anti-aquaporin-4 (AQP4) auto-antibodies represent approximately three quarters of all patients with NMOSD.4,5,6,7 The disease primarily affects women.11 There are currently no approved therapies for this disease.
In patients with NMOSD, the body’s own immune system can turn on itself to produce auto-antibodies (immunoglobulin G [IgG)]) against AQP4, a protein on certain cells in the brain and spinal cord that are critical for the survival of nerve cells. The binding of these anti-AQP4 auto-antibodies activates the complement cascade, another part of the immune system. Complement activation by anti-AQP4 auto-antibodies leads to destruction of vital cells in the CNS, leading to demyelination and to the death of neurons, predominantly in the spinal cord and optic nerve, which ultimately results in blindness, paralysis, and sometimes death.12,13,14,15,16
About the PREVENT Study
The Prevention of Relapses and Evaluation of Eculizumab in NMOSD Treatment (PREVENT) study was a multinational, double-blind, parallel-group Phase 3 time-to-event study that assessed the efficacy and safety of Soliris® (eculizumab) compared to placebo for the treatment of patients with anti-aquaporin-4 (AQP4) auto antibody-positive neuromyelitis optica spectrum disorder (NMOSD). The study enrolled 143 adult patients who were randomized 2:1 to the Soliris® and placebo treatment arms. Patients needed to have a confirmed diagnosis of NMOSD, be seropositive for anti-AQP4 auto-antibodies (also called NMO-immunoglobulin G [IgG] antibodies), and have a history of at least two relapses in the last 12 months or three relapses in the last 24 months, with at least one relapse in the 12 months prior to screening. Patients were allowed to receive stable maintenance dose of protocol permitted supportive immune suppressive therapies for relapse prevention.
The primary endpoint was the time to first on-trial relapse as adjudicated by an independent committee comprised of three external experts in neurology/neuro-ophthalmology who were blinded to treatment. Adjudication decisions were based on objective and consistent clinical criteria described in a relapse adjudication charter. Secondary endpoints included adjudicated on-trial annualized relapse rate, and others assessing disability and quality of life, as well as safety and tolerability measures. Pre-specified sensitivity analyses include various types of statistical analyses of the time to relapse, and of secondary endpoints.
The study met its primary endpoint of time to first adjudicated on-trial relapse, demonstrating that treatment with Soliris® reduced the risk of NMOSD relapse by 94.2 percent compared to placebo (p < 0.0001). At 48 weeks, 97.9 percent of patients receiving Soliris® were free of relapse compared to 63.2 percent of patients receiving placebo. Treatment with Soliris® reduced the adjudicated on-trial annualized relapse rate compared to placebo, a key secondary endpoint, by 95.5 percent (p<0.0001).
While results favored Soliris® on the other secondary endpoints, which included disability and quality of life measures, the observed differences were small. This was not unexpected since disease worsening in NMOSD is driven by damage incurred following relapse. Follow-up for assessment of long-term disability was limited by the trial design, which permitted patients to transition to the open-label study six weeks after the relapse, where all patients received Soliris®. Soliris® was generally well tolerated with a safety profile consistent with that seen in previous clinical studies and real-world use in its three approved indications. No cases of meningococcal infection were observed.
The treatment duration for an individual patient varied as this was a time-to-event study. Patients who completed the study either because of a relapse or because the study ended were provided with the opportunity to enter an extension study to receive open-label Soliris®. One hundred and nineteen patients entered the extension study.
Alexion will host a conference call/webcast today,
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,
Soliris® has received Orphan Drug Designation (ODD) for the
treatment of patients with PNH in the U.S., EU,
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
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. 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.
Alexion is a global biopharmaceutical company focused on serving patients and families affected by rare diseases through the discovery, development, and commercialization of life-changing therapies. As the global leader in complement biology and inhibition for more than 20 years, Alexion 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). Alexion also 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). In addition, the company is developing two late-stage therapies, a second complement inhibitor and a copper-binding agent for Wilson disease. 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. Alexion has been named to the
This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, including statements related to: the impact that the relapse reduction could have for patients with NMOSD using Soliris®, complement inhibition can play a critical role in treating NMOSD, Soliris® may be a promising new treatment for NMOSD and a turning point in the treatment of this condition for patients and their families, the future planned submission of regulatory applications for review and approval by regulatory authorities in the U.S., the
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Alexion Pharmaceuticals, Inc.
Arne Naeveke, PhD, 857-338-8597
Susan Altschuller, PhD, 857-338-8788