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New Data Presented at ASH Annual Meeting Enhance Understanding of PNH and aHUS to Provide Optimal Care for Patients with These Life-threatening DisordersCHESHIRE, Conn. --(Business Wire)-- Alexion Pharmaceuticals, Inc. (Nasdaq: ALXN) today announced that researchers presented data from clinical trials demonstrating the clinical benefits of chronic Soliris® (eculizumab) treatment in patients with atypical hemolytic uremic syndrome (aHUS) as well as new patient registry data providing further insight into optimal care for patients with paroxysmal nocturnal hemoglobinuria (PNH) at the American Society of Hematology (ASH) 55th Annual Meeting and Exposition in New Orleans. Data included:
Soliris, a first-in-class terminal complement inhibitor, specifically targets uncontrolled complement activation. It is the first and only approved treatment for patients with PNH, a debilitating, ultra-rare and life-threatening blood disorder characterized by complement-mediated hemolysis (destruction of red blood cells). Soliris is approved in nearly 50 countries for the treatment of PNH, including the United States, European Union and Japan. Soliris is also approved in the United States, European Union, Japan and other countries as the first and only treatment for pediatric and adult patients with aHUS, a genetic, chronic, ultra-rare disease associated with vital organ failure and premature death. "Extensive clinical data presented at ASH demonstrate a significant and sustained inhibition of complement-mediated TMA with Soliris treatment and support the chronic use of Soliris in pediatric and adult patients with aHUS. New biomarker data also reinforce the need for chronic terminal complement inhibition in patients with aHUS and suggest that a loss of terminal complement inhibition could lead to a marked increase in thrombotic risk with the potential for sudden and catastrophic damage to vital organs," said Leonard Bell, M.D., Chief Executive Officer of Alexion. "Additionally, new findings from the largest PNH registry highlight the importance of understanding risk factors and ongoing monitoring of PNH patients to achieve the best possible outcomes. We are pleased that new data continue to enhance the understanding of PNH and aHUS so that we can optimize care for patients with these life-threatening and ultra-rare disorders." Biomarkers in Patients with aHUS Treated with Soliris (Abstract 2184)1 In a poster session today, researchers presented biomarker data from a prospective open-label trial of adult patients with aHUS treated with Soliris. The data show that at baseline, prior to Soliris treatment initiation, patients with aHUS have significantly elevated levels of all biological measures of complement-mediated TMA compared to normal healthy volunteers. Prior to Soliris treatment, in all aHUS patient groups-- including those receiving PE/PI or those with normal platelets, haptoglobin (Hp) or lactate dehydrogenase (LDH) levels--patients demonstrated significant elevation in terminal complement activation that was 45-305 fold higher than levels in normal healthy volunteers. In addition, patients with aHUS had significant elevation in measures of vascular inflammation, endothelial activation and damage, thrombotic risk, vital organ damage and proximal complement alternative pathway (CAP) activation. Sustained Soliris treatment significantly reduced and normalized highly elevated measures of terminal complement activation, and resulted in:
Sustained inhibition of terminal complement activation with Soliris dramatically reduced and normalized measures of vital organ damage, and also significantly reduced measures of proximal CAP activation. The study authors concluded that a loss of terminal complement inhibition in aHUS would be expected to lead to an increase in underlying subclinical endothelial activation, significant acceleration of endothelial damage, marked increase in thrombotic risk, and an early, ongoing risk of catastrophic vascular ischemia and vital organ damage. Further, in clinical trials of patients with aHUS, severe TMA complications have been observed in patients following a missed dose of Soliris.7 "The biomarker data in this study suggest that chronic terminal complement blockade with Soliris is necessary to protect patients from the potentially catastrophic consequences of aHUS, including vital organ failure and premature death," said Camille L. Bedrosian, M.D., Chief Medical Officer of Alexion Pharmaceuticals. "These data point to the chronic nature of aHUS and the need for continuous treatment in order to achieve optimal outcomes for patients with this genetic and life-long disease." Soliris in Pediatric and Adult Patients with aHUS
Data in Patients with PNH The ASH meeting also featured the following data presentations in patients with PNH:
About aHUS aHUS is a chronic, ultra-rare, and life-threatening disease in which a genetic deficiency in one or more complement regulatory genes causes chronic uncontrolled complement activation, resulting in complement-mediated thrombotic microangiopathy (TMA), the formation of blood clots in small blood vessels throughout the body.14,15 Permanent, uncontrolled complement activation in aHUS causes a life-long risk for TMA, which leads to sudden, catastrophic, and life-threatening damage to the kidney, brain, heart, and other vital organs, and premature death.14,16 Complement-mediated TMA also causes reduction in platelet count (thrombocytopenia) and red blood cell destruction (hemolysis). aHUS affects both children and adults. Sixty-five percent of all patients with aHUS die, require kidney dialysis, or have permanent kidney damage within the first year after diagnosis despite supportive care with plasma exchange or plasma infusion (PE/PI).17,18 The majority of patients with aHUS who receive a kidney transplant experience subsequent systemic TMA, resulting in a 90% transplant failure rate in these TMA patients.19 While mutations have been identified in at least ten different complement regulatory genes, mutations are not identified in 30-50% of patients with a confirmed diagnosis of aHUS.20 About PNH PNH is an ultra-rare blood disorder in which chronic, uncontrolled activation of complement, a component of the normal immune system, results in hemolysis (destruction of the patient's red blood cells). PNH strikes people of all ages, with an average age of onset in the early 30s.21 Approximately 10% of all patients first develop symptoms at 21 years of age or younger.22 PNH develops without warning and can occur in men and women of all races, backgrounds and ages. PNH often goes unrecognized, with delays in diagnosis ranging from one to more than 10 years.23 In the period of time before Soliris was available, it had been estimated that approximately one-third of patients with PNH did not survive more than five years from the time of diagnosis.21 PNH has been identified more commonly among patients with disorders of the bone marrow, including aplastic anemia (AA) and myelodysplastic syndromes (MDS).24,25,26 In patients with thrombosis of unknown origin, PNH may be an underlying cause.21 About Soliris 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 US (2007), European Union (2007), Japan (2010) and other countries as the first and only treatment for patients with paroxysmal nocturnal hemoglobinuria (PNH), a debilitating, ultra-rare and life-threatening blood disorder, characterized by complement-mediated hemolysis (destruction of red blood cells). Soliris is indicated to reduce hemolysis. Soliris is also approved in the US (2011), the European Union (2011), Japan (2013) and other countries as the first and only treatment for patients with atypical hemolytic uremic syndrome (aHUS), a debilitating, ultra-rare and life-threatening genetic disorder characterized by complement-mediated thrombotic microangiopathy, or TMA (blood clots in small vessels). Soliris is indicated to inhibit complement-mediated TMA. The effectiveness of Soliris in aHUS is based on the effects on TMA and renal function. Prospective clinical trials in additional patients, the preliminary results of which are reported here at ASH are ongoing to confirm the benefit of Soliris in patients with aHUS. Soliris is not indicated for the treatment of patients with Shiga-toxin E. coli related hemolytic uremic syndrome (STEC-HUS). For the breakthrough innovation in complement inhibition, Alexion and Soliris have received the pharmaceutical industry's highest honors: the 2008 Prix Galien USA Award for Best Biotechnology Product with broad implications for future biomedical research and the 2009 Prix Galien France Award in the category of Drugs for Rare Diseases. More information including the full U.S. prescribing information on Soliris is available at www.soliris.net. The full prescribing information for Soliris in Europe, is available at: http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/000791/human_med_001055.jsp&mid=WC0b01ac058001d124. Important Safety Information The US product label for Soliris includes a boxed warning: "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 Advisory Committee on Immunization Practices (ACIP) recommendations for meningococcal vaccination in patients with complement deficiencies. Immunize patients with a meningococcal vaccine at least 2 weeks prior to administering the first dose of Soliris, unless the risks of delaying Soliris therapy outweigh the risk of developing a meningococcal infection. (See Serious Meningococcal Infections (5.1) for additional guidance on the management of 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)." In patients with PNH, the most frequently reported adverse events observed with Soliris treatment in clinical studies were headache, nasopharyngitis (runny nose), back pain and nausea. 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 aHUS, the most frequently reported adverse events observed with Soliris treatment in clinical studies were hypertension, upper respiratory tract infection, diarrhea, headache, anemia, vomiting, nausea, urinary tract infection, and leukopenia. Please see full prescribing information for Soliris, including boxed WARNING regarding risk of serious meningococcal infection. About Alexion Alexion Pharmaceuticals, Inc. is a biopharmaceutical company focused on serving patients with severe and ultra-rare disorders through the innovation, development and commercialization of life-transforming therapeutic products. Alexion is the global leader in complement inhibition and has developed and markets Soliris® (eculizumab) as a treatment for patients with PNH and aHUS, two debilitating, ultra-rare and life-threatening disorders caused by chronic uncontrolled complement activation. Soliris is currently approved in nearly 50 countries for the treatment of PNH, and in the United States, European Union, Japan and other countries for the treatment of aHUS. Alexion is evaluating other potential indications for Soliris in additional severe and ultra-rare disorders beyond PNH and aHUS, and is developing other highly innovative biotechnology product candidates across multiple therapeutic areas. This press release and further information about Alexion Pharmaceuticals, Inc. can be found at: www.alexionpharma.com. [ALXN-G] Safe Harbor Statement This news release contains forward-looking statements, including statements related to anticipated clinical development, regulatory and commercial milestones and potential health and medical benefits of Soliris® (eculizumab) for the potential treatment of patients with PNH and aHUS. 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 Soliris for its current or potential new indications, and a variety of other risks set forth from time to time in Alexion's filings with the 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 September 30, 2013, and in Alexion's other filings with the 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.
1 Cofiell R, Kukreja A, Bedard K, et al. Biomarkers of Complement and Endothelial Activation, Inflammation, Thrombosis and Renal Injury In Patients (pts) with aHUS Treated with Eculizumab (ECU). Presented at the 55th Annual Meeting of the American Society of Hematology (ASH), New Orleans, LA, December 8, 2013: Abstract 2184. 2 Greenbaum L, Fila M, Ardissino G, et al. Eculizumab (ECU) Inhibits Thrombotic Microangiopathy (TMA) and Improves Renal Function In Pediatric Patients (Pts) with Atypical Hemolytic Uremic Syndrome (aHUS). Presented at the 55th Annual Meeting of the American Society of Hematology (ASH), New Orleans, LA, December 8, 2013: Abstract 2191. 3 Fadi F, Hourmant M, Cataland SR, et al. Eculizumab (ECU) Inhibits Thrombotic Microangiopathy (TMA) and Improves Renal Function In Adult Patients (Pts) With Atypical Hemolytic Uremic Syndrome (aHUS). Presented at the 55th Annual Meeting of the American Society of Hematology (ASH), New Orleans, LA, December 8, 2013: Abstract 2179. 4 Lee JW, Jang HK, Kim JS, et al. Clinical Signs and Symptoms in Non-Transfused Patients with Paroxysmal Nocturnal Hemoglobinuria from a Korean Prospective PNH Registry. Presented at the 55th Annual Meeting of the American Society of Hematology (ASH), New Orleans, LA, December 9, 2013: Abstract 3720. 5 Obara N, Chiba S, Hosokawa K, et al. Baseline Assessment of GPI-Anchored Protein Deficient Blood Cells in Patients with Bone Marrow Failure (The OPTIMA Study). Presented at the 55th Annual Meeting of the American Society of Hematology (ASH), New Orleans, LA, December 7, 2013: Abstract 1241. 6 Villegas A, Gaya A, Ojeda E, et al. Periodic Evaluation of the Cline Size is Mandatory in PNH: Study of the Spanish Cohort of the International PNH Registry. Presented at the 55th Annual Meeting of the American Society of Hematology (ASH), New Orleans, LA, December 9, 2013: Abstract 3715. 7 Soliris® (eculizumab) Prescribing Information. Cheshire, CT: Alexion Pharmaceuticals, Inc.; 2012. 8 Soliris® (eculizumab) Inhibits TMA and Improves Renal Function in Pediatric and Adult Patients with atypical Hemolytic Uremic Syndrome (aHUS). Alexion Pharmaceuticals, Inc.: November 9, 2013. http://news.alexionpharma.com/press-release/product-news/soliris%C2%A0eculizumab-inhibits-tma-and-improves-renal-function-pediatric-and. 9 Dr. Larry Greenbaum receives research support from Alexion Pharmaceuticals, Inc. and is a consultant to the company. 10 Dr. Fadi Fakhouri receives research support from Alexion Pharmaceuticals, Inc. and is a consultant to the company. 11 Licht C, Muus P, Legendre C, et al. Time to Hematologic and Renal Improvements in Atypical Hemolytic Uremic Syndrome Patients with Long Disease Duration and Chronic Kidney Disease (CKD) Treated with Eculizumab. Presented at the 55th Annual Meeting of the American Society of Hematology (ASH), New Orleans, LA, December 8, 2013: Abstract 2186. 12 Muus P, Bedrosian CL, Furman RR, et al. Time to Hematologic and Renal Improvements in aHUS Patients with Progressing Thrombotic Microangiopathy Treated with Eculizumab Over Two Years. Presented at the 55th Annual Meeting of the American Society of Hematology (ASH), New Orleans, LA, December 9, 2013: Abstract 3426. 13 Dr. Jong Wook Lee receives research support from Alexion Pharmaceuticals, Inc. and is a consultant to the company. 14 Benz K, Amann K. Thrombotic microangiopathy: new insights. Curr Opin Nephrol Hypertens. 2010;19(3):242-7. 15 Ariceta G, Besbas N, Johnson S, et al. Guideline for the investigation and initial therapy of diarrhea-negative hemolytic uremic syndrome. Pediatr Nephrol. 2009;24:687-96. 16 Tsai HM. The molecular biology of thrombotic microangiopathy. Kidney Int. 2006;70(1):16-23. 17 Caprioli J, Noris M, Brioschi S, et al. The impact of MCP, CFH, and IF mutations on clinical presentation, response to treatment, and outcome. Blood. 2006;108:1267-9. 18 Loirat C, Garnier A, Sellier-Leclerc AL, Kwon T. Plasmatherapy in atypical hemolytic uremic syndrome. Semin Thromb Hemost. 2010;36:673-81. 19 Bresin E, Daina E, Noris M, et al. Outcome of renal transplantation in patients with non-Shiga toxin-associated hemolytic uremic syndrome: prognostic significance of genetic background. Clin J Am Soc Nephrol. 2006;1:88-99. 20 Noris M, Caprioli J, Bresin E, et al. Relative role of genetic complement abnormalities in sporadic and familial aHUS and their impact on clinical phenotype. Clin J Am Soc Nephrol. 2010;5:1844-59. 21 Socié G, Mary JY, de Gramont A, et al. Paroxysmal nocturnal haemoglobinuria: long-term follow-up and prognostic factors. Lancet. 1996: 348:573-577. 22 Parker C, Omine M, Richards S, et al. Diagnosis and management of paroxysmal nocturnal hemoglobinuria. Blood. 2005;106(12):3699-3709. 23 Hillmen P, Lewis SM, Bessler M, Luzzatto L, Dacie JV. Natural history of paroxysmal nocturnal hemoglobinuria. N Engl J Med. 1995;333:1253-1258. 24 Wang H, Chuhjo T, Yasue S, Omine M, Naka S. Clinical significance of a minor population of paroxysmal nocturnal hemoglobinuria-type cells in bone marrow failure syndrome. Blood. 2002;100 (12):3897-3902. 25 Iwanga M, Furukawa K, Amenomori T, et al. Paroxysmal nocturnal haemoglobinuria clones in patients with myelodysplastic syndromes. Br J Haematol. 1998;102(2):465-474. 26 Maciejewski JP, Rivera C, Kook H, Dunn D, Young NS. Relationship between bone marrow failure syndromes and the presence of glycophosphatidyl inositol-anchored protein-deficient clones. Br J Haematol. 2001;115:1015-1022.
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