On November 1, 2018 Alexion Pharmaceuticals, Inc. (NASDAQ:ALXN) reported that nine abstracts from its complement research and development program have been accepted for presentation at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in San Diego, December 1 to 4, 2018 (Press release, Alexion, NOV 1, 2018, View Source [SID1234530490]). Key data will include both new analyses and previously announced results from the two Phase 3 studies of ALXN1210, the Company’s investigational long-acting C5 complement inhibitor, in patients with paroxysmal nocturnal hemoglobinuria (PNH), in addition to further data on Soliris (eculizumab) for the treatment of PNH and atypical hemolytic uremic syndrome (aHUS). Collectively, the breadth of the data to be presented at ASH (Free ASH Whitepaper) demonstrates continued progress extending the company’s leadership in understanding and treating rare complement-mediated diseases.
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The accepted abstracts are listed below and are now available on the ASH (Free ASH Whitepaper) website.
ALXN1210
A Phase 3 Study of Ravulizumab (ALXN1210) versus Eculizumab in Adults with Paroxysmal Nocturnal Hemoglobinuria Naive to Complement Inhibitors: Results of a Subgroup Analysis with Patients Stratified by Baseline Hemolysis Level, Transfusion History, and Demographics. Abstract ID#: 110623 – Oral Presentation, December 3, 2018, 11:00-11:15 a.m. PST, Grand Hall C.
Results from a Phase 3, Multicenter, Non-Inferiority Study of Ravulizumab (ALXN1210) Versus Eculizumab in Adult Patients with Paroxysmal Nocturnal Hemoglobinuria Currently Treated with Eculizumab. Abstract ID#: 119147 – Oral Presentation, December 3, 10:30-10:45 a.m. PST, Grand Hall C.
Ravulizumab (ALXN1210) versus Eculizumab in Adults with Paroxysmal Nocturnal Hemoglobinuria: Pharmacokinetics and Pharmacodynamics Observed in Two Phase 3 Randomized, Multicenter Studies. Abstract ID#: 110858 – Oral Presentation, December 3, 10:45-11:00 a.m. PST, Grand Hall C.
A Prospective Analysis of Breakthrough Hemolysis in 2 Phase 3 Randomized Studies of Ravulizumab (ALXN1210) versus Eculizumab in Adults with Paroxysmal Nocturnal Hemoglobinuria. Abstract ID#: 110874 – Poster Presentation, December 2, 6:00-8:00 p.m. PST, Hall GH.
Soliris (eculizumab)
Efficacy of Eculizumab in Pediatric Patients with Paroxysmal Nocturnal Hemoglobinuria in the International PNH Registry. Abstract ID#: 111306 – Poster Presentation, December 3, 6:00-8:00 p.m. PST, Hall GH.
Economic Benefit of Early In-hospital Diagnosis and Treatment Initiation of Eculizumab in aHUS. Abstract ID#: 112893 – Poster Presentation, December 2, 6:00-8:00 p.m. PST, Hall GH.
PNH
Prognostic Value of Clone Size in Paroxysmal Nocturnal Hemoglobinuria (PNH) for Thrombotic Events in Untreated Patients in the International PNH Registry. Abstract ID#: 111324 – Poster Presentation, December 1, 6:15-8:15 p.m. PST, Hall GH.
Baseline Characteristics of Patients with Paroxysmal Nocturnal Hemoglobinuria Identified in the Department of Defense Database. Abstract ID#: 113478 – online.
The Value of Population Based Data to Study Rare Diseases: An Example Using the Department of Defense Healthcare System. Abstract ID#: 113497 – online.
About Paroxysmal Nocturnal Hemoglobinuria (PNH)
Paroxysmal nocturnal hemoglobinuria (PNH) is a chronic, progressive, debilitating, and potentially life-threatening ultra-rare blood disorder that can strike men and women of all races, backgrounds, and ages without warning, with an average age of onset in the early 30s.1,2,3 PNH often goes unrecognized, with delays in diagnosis ranging from one to more than 10 years.2 In patients with PNH, chronic, uncontrolled activation of the complement system, a component of the body’s immune system, results in hemolysis (the destruction of red blood cells)4, which in turn can result in progressive anemia, fatigue, dark urine, and shortness of breath.5,6,7 The most devastating consequence of chronic hemolysis is thrombosis (the formation of blood clots), which can damage vital organs and cause premature death.8 Historically, it had been estimated that one in three patients with PNH did not survive more than five years from the time of diagnosis.2 PNH is more common among patients with disorders of the bone marrow, including aplastic anemia (AA) and myelodysplastic syndromes (MDS).9,10,11 In certain patients with thrombosis of unknown origin, PNH may be an underlying cause.4
About ALXN1210
ALXN1210 is an innovative, investigational, long-acting C5 inhibitor discovered and developed by Alexion that works by inhibiting the C5 protein in the terminal complement cascade, a part of the body’s immune system that, when activated in an uncontrolled manner, plays a role in severe ultra-rare disorders like paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), and anti-acetylcholine receptor (AchR) antibody-positive myasthenia gravis (MG). In Phase 3 clinical studies in complement inhibitor-naïve patients with PNH, and patients with PNH who had been stable on Soliris, intravenous treatment with ALXN1210 every eight weeks demonstrated non-inferiority to intravenous treatment with Soliris every two weeks, with numeric results for all primary and key secondary endpoints favoring ALXN1210. ALXN1210 is also currently being evaluated in a Phase 3 clinical study in complement inhibitor-naïve patients with aHUS, administered intravenously every eight weeks. In addition, Alexion plans to initiate a Phase 3 clinical study of ALXN1210 delivered subcutaneously once per week as a potential treatment for patients with PNH and aHUS.
ALXN1210 has received Orphan Drug Designation (ODD) for the treatment of patients with PNH in the U.S., EU, and Japan, and for the subcutaneous treatment of patients with aHUS in the U.S.
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, Japan, and other countries as the first and only treatment for patients with PNH and aHUS, in the EU as the first and only treatment of refractory generalized MG (gMG) in adults who are anti-AchR antibody-positive, in the U.S. for the treatment of adult patients with gMG who are anti-AchR antibody-positive, and in Japan for the treatment of patients with gMG who are AChR antibody-positive and whose symptoms are difficult to control with high-dose intravenous immunoglobulin (IVIG) therapy or plasmapheresis (PLEX). Soliris is not indicated for the treatment of patients with Shiga-toxin E. coli-related hemolytic uremic syndrome (STEC-HUS).
Soliris has received Orphan Drug Designation (ODD) for the treatment of patients with PNH in the U.S., EU, Japan, and many other countries, for the treatment of patients with aHUS in the U.S., EU, and many other countries, for the treatment of patients with MG in the U.S. and EU, for the treatment of patients with refractory gMG in Japan, and for the treatment of patients with neuromyelitis optica spectrum disorder (NMOSD) in the U.S., EU, and Japan. 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. 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.