New Data Show Majority of Patients with aHUS Experienced Systemic Multi-Organ Complications Prior to Treatment

Alexion Pharmaceuticals today announced the presentation of data that underscore the critical need for testing patients at high risk for paroxysmal nocturnal hemoglobinuria (PNH) and new data on the potentially life-threatening, systemic complications in patients with atypical hemolytic uremic syndrome (aHUS).

A retrospective analysis of 30 pediatric and adult patients with aHUS showed that the majority of patients experienced severe complications of the disease across multiple organs, despite receiving supportive care, including plasma exchange or plasma infusion. These data underscore the risk for sudden and potentially fatal systemic complications of aHUS.1 In a separate analysis of 19 pediatric patients with aHUS, Soliris® (eculizumab) significantly reduced thrombotic microangiopathy, or TMA (the formation of blood clots in small blood vessels throughout the body), leading to improved kidney function and eliminating the need for dialysis in half of patients who previously required it before starting on Soliris therapy.2 These data were presented at the 17th Congress of the European Hematology Association (EHA), being held in Amsterdam on June 14-17.

“The research presented at EHA confirms the significant and potentially fatal risks of both PNH and aHUS, two debilitating, ultra-rare and life-threatening disorders caused by chronic uncontrolled complement activation, and the urgent need for an accurate diagnosis and rapid treatment in these patients,” said Leonard Bell, M.D., Chief Executive Officer of Alexion.

Systemic Multi-Organ Complications Common in Patients with aHUS

In a poster session on Friday, June 15, researchers presented retrospective data from an analysis of 30 pediatric and adult patients with aHUS prior to receiving Soliris. All 30 patients (100%) showed evidence of kidney impairment. Extra-renal, systemic organ complications were reported in 63% of patients (19 of 30), and extra-renal thrombi were reported in 37% of patients (11 of 30).1 These complications spanned the cardiovascular (47% of patients), gastrointestinal (37%) and neurological (20%) systems, and were similarly reported in aHUS patients with or without identified genetic complement mutation.1

“While aHUS often has a devastating impact on the kidneys, the TMA process that defines aHUS can also cause progressive and sudden damage across multiple organs, including heart attack, stroke, pancreatitis, deep vein thrombosis and seizures,” said Craig B. Langman, M.D., the Isaac A Abt MD Professor of Kidney Diseases, Head of Kidney Diseases, Feinberg School of Medicine, Northwestern University. “Evidence of TMA or progressive systemic organ involvement should prompt high suspicion of aHUS as a clinical diagnosis, even in the absence of kidney failure.”

Pediatric Data Shows Consistent Results with Prospective Trials in Adult and Adolescent Patients with aHUS

In an oral presentation on Sunday, June 17, researchers presented an analysis of retrospective data from 19 pediatric patients (<18 years of age) with aHUS who received Soliris therapy. In this analysis, which is also summarized in part in the Soliris product label, treatment with Soliris inhibited uncontrolled complement activation in all evaluable patients, inhibited complement-mediated TMA, and demonstrated platelet count normalization in 89% of patients (17 of 19). Soliris also reduced the burden of TMA interventions, as demonstrated by a reduced need for plasma exchange/plasma infusion (PE/PI) in all patients who had previously received it. Kidney function was also markedly improved with Soliris treatment, eliminating the need for dialysis in half of patients who previously required it (4 of 8 patients), and no new dialysis was required in any pediatric patient.2 The most common adverse events reported were pyrexia, diarrhea, vomiting, upper respiratory tract infection, cough, vomiting, nasal congestion, and tachycardia. Efficacy and safety outcomes were similar across all pediatric age groups with Soliris treatment.2

“The efficacy and safety outcomes of Soliris in pediatric patients with aHUS are consistent with the prospective, controlled trials of adult and adolescent patients with aHUS,” commented Dr. Ramon Vilalta, Hospital Vall d’Hebron in Barcelona, Spain who presented the data. “These data support the role of Soliris as the only approved treatment for aHUS patients of any age.”

Support for Testing High-Risk Patients for PNH

In a poster session on June 16, the need to test and monitor high-risk patients for PNH was confirmed by results of an analysis of 7,699 patients whose blood cells were screened for a PNH clone using high-sensitivity flow cytometry (HSFC), according to the recommendations by the International Clinical Cytometry Society (ICCS). In the analysis, which was previously presented at the American Society of Hematology (ASH) annual meeting in December 2011, ICD-9 Diagnostic Codes were used to identify patients who had clinical indications for PNH testing in accordance with the ICCS guidelines.3 The analysis found that PNH clones greater than 0.01% were detected in 26% of patients with an ICD-9 diagnosis of aplastic anemia (AA), as well as in 23% of patients with hemolytic anemia (including patients with known PNH), 13% of patients with hemoglobinuria and 6% of patients with hemolysis.3 In addition, among patients with bone marrow failure syndromes other than AA, 5% of patients with unexplained cytopenia, 6% of patients with myelodysplastic syndrome, and 3% of patients with anemia (unspecified or in chronic illness) tested positive for a PNH clone. In addition, the need to monitor patients with small PNH clones was confirmed as 50% of patients with PNH clone sizes between 0.1%-10% showed variation in clone size during follow-up studies.3

“Patients in high-risk populations for PNH should be consistently tested and monitored based on the ICCS recommendations to ensure accurate diagnosis and early intervention,” said lead investigator Mayur K. Movalia, M.D.,Pathology, Dahl-Chase Diagnostic Services, Bangor, Maine.

Multicenter Study Found Soliris Reduced LDH in Pediatric Patients with PNH

In a poster session on June 16, researchers presented data from a 12-week, open-label multicenter study of Soliris in children and adolescents (ages 2 to 17 years) with paroxysmal nocturnal hemoglobinuria (PNH).4 The study, which was previously reported at the ASH 2011 annual meeting, showed that Soliris treatment led to a rapid and sustained reduction in LDH levels, from a mean of 1,020 U/L at baseline to within normal range (275/U/L) by the second week of treatment.4 The safety and adverse event profile for Soliris was consistent with that reported in adult Phase 3 PNH clinical trials.4

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.5,6 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.6.7 Sixty-five percent of all patients with aHUS die, require kidney dialysis or have permanent kidney damage within the first year after diagnosis despite plasma exchange or plasma infusion (PE/PI).8,9 The majority of patients with aHUS who receive a kidney transplant commonly experience subsequent systemic TMA, resulting in a 90% transplant failure rate.10

aHUS affects both children and adults. In a large group of aHUS patients, 60% were first diagnosed at younger than 18 years of age.11 Complement-mediated TMA also causes reduction in platelet count (thrombocytopenia) and red blood cell destruction (hemolysis). 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.11

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.12 Approximately 10 percent of all patients first develop symptoms at 21 years of age or younger.13 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.14 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.13 PNH has been identified more commonly among patients with disorders of the bone marrow, including aplastic anemia (AA) and myelodysplastic syndromes (MDS).15,16,17 In patients with thrombosis of unknown origin, PNH may be an underlying cause.12

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, European Union, Japan 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 also approved in the US and the European Union 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 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). Alexion’s breakthrough approach in complement inhibition has 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 prescribing information on Soliris is available at

Important Safety Information

The U.S. 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 (5.2). 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 more than 40 countries for the treatment of PNH, and in the United States and the European Union for the treatment of aHUS. Alexion is evaluating other potential indications for Soliris and is developing four other highly innovative biotechnology product candidates. This press release and further information about Alexion Pharmaceuticals, Inc. can be found at: