Alexion Pharmaceuticals, Inc. (Nasdaq: ALXN) today announced the presentation of new data demonstrating the long-term benefits of Soliris ® (eculizumab) in 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). Data including the clinical benefits of Soliris in the treatment of patients with PNH and atypical hemolytic uremic syndrome (aHUS) were presented at the 54th Annual Meeting of the American Society of Hematology (ASH) in Atlanta:
- Ten-year data from a large cohort of patients with PNH from the United Kingdom (UK) confirm the long-term safety and efficacy of chronic Soliris therapy and demonstrate the impact of Soliris on quality of life.1
- The long-term safety of Soliris was also demonstrated in PNH clinical development trials in which patients were treated continuously with Soliris and followed for up to 5.5 years.2
- Data from an international PNH registry showed that Soliris significantly reduced the risk of thromboembolism (TE) in patients with PNH.3
- Researchers from South Korea presented data confirming that hemolysis is an independent risk factor for TE in patients with PNH.4
- Researchers in Japan observed a rare genetic polymorphism in the terminal complement protein C5 in Japanese patients with PNH who had no or minimal reduction in lactate dehydrogenase (LDH) while on Soliris therapy (9 out of 250 treated, or 3.6%).5
- The ASH meeting also featured presentations of two-year data highlighting the long-term benefits of chronic Soliris therapy in patients with aHUS,6,7 an ultra-rare, genetic disease characterized by complement-mediated thrombotic microangiopathy (TMA), the formation of blood clots in small vessels throughout the body.
“Extensive clinical data and real-world clinical experience spanning more than 10 years further establish the benefits that Soliris is providing to patients with PNH,” said Leonard Bell, M.D., Chief Executive Officer of Alexion. “The presentation of the two-year aHUS data also demonstrates the continued benefits of long-term Soliris therapy in patients with aHUS, and underscores the important role of hematologists in diagnosing and treating patients with this severe and ultra-rare complement-mediated disease.”Ten-Year Experience with Soliris in All Patients with PNH Treated in the UK In a poster presentation today, researchers presented data from all 153 patients who participated in a nationally commissioned PNH service led by two UK medical centers. The objective of the study was to describe the long-term safety, efficacy, and outcomes in patients with PNH from the UK who received Soliris treatment from May 2002 to April 2012. 1 The results demonstrated that the significant clinical benefits and long-term safety of Soliris were sustained over 10 years of chronic treatment. The investigators reported that long-term Soliris treatment led to an improvement in survival when compared with historical controls, and a significant reduction in the incidence of TE. 8,9 Researchers also reported data on the effect of discontinuation of anti-coagulant therapy in selected PNH patients. Transfusion independence was observed in the majority of patients, and the number of units transfused was significantly reduced in those patients still receiving transfusions. Results also confirmed the long-term safety and efficacy of continuous Soliris treatment. 1 Researchers presented the following data in support of these conclusions: 1
- Long-term Soliris therapy significantly reduced intravascular hemolysis by 83.4%, as assessed by levels of LDH (p<0.001).
- The researchers noted that UK patients on long-term Soliris therapy had improved survival compared with previously published historical controls.8,9 Researchers also compared the survival of PNH patients treated with Soliris to a normal population of the same age and gender. Although the survival of PNH patients after 10 years of Soliris therapy was slightly inferior to this normal healthy population group, the causes of death in PNH patients were related to bone marrow failure and not due to hemolysis or TE associated with the underlying PNH.
- In the 12 months prior to starting Soliris, 36 thrombotic episodes were reported in 22 patients. None of those patients had a further thrombotic episode while on Soliris therapy. In the most recent 12 months on therapy, TEs were significantly reduced with only 3 events reported in a total of 3 patients (p<0.05).
- Of 117 patients transfused in the 12 months before receiving Soliris, 77 (65.8%) were transfusion-independent in the most recent 12 months on treatment. Among those patients still receiving transfusions (n=40), there was a significant 69% reduction in the number of units transfused, from a median of 26 units, 12 months before therapy, to 8 units in the most recent 12 months on therapy (P<0.05).
- In a poster presentation on December 8, researchers in South Korea evaluated the risk of TE in patients with PNH and elevated hemolysis (as identified by LDH ≥1.5 x ULN) in addition to any of the four clinical symptoms of abdominal pain, chest pain, dyspnea, or hemoglobinuria, compared with patients who had elevated LDH alone. The analyses confirm that elevated hemolysis was associated with a seven-fold increased risk of TE in patients with PNH. The risk of TE was significantly further increased in patients with elevated hemolysis and additional symptoms of abdominal pain, chest pain, dyspnea or hemoglobinuria compared with patients without the symptom and LDH <1.5 x ULN. These results underscore the importance of early therapeutic intervention and monitoring of PNH patients with elevated LDH.4
- In a separate poster presentation on December 8, data supported the need to test high-risk PNH patients for diagnostic markers as an aid to treatment selection. Researchers presented an updated analysis of 7,699 high-risk patients whose blood cells were screened for a PNH clone using high-sensitivity flow cytometry. Among the 481 PNH-positive patients, those with large PNH clone sizes (>20%) were found to be more likely to have clinical symptoms, particularly those associated with hemolysis, and were thus deemed more likely to benefit from therapy.13
- A poster presentation today identified a polymorphism in the terminal complement protein C5 that appears to be associated with no or minimal reduction in LDH in nine Japanese patients with PNH who received Soliris therapy, although there is no evidence of the mutation outside of Japan or in any other Asian populations. The study authors concluded that further research is needed to verify that the polymorphism in the C5 gene is responsible for the suboptimal reduction in LDH and to determine a more accurate prevalence of this C5 polymorphism in Japanese populations.5
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 www.soliris.net. 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 (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, which are being investigated across eight severe and ultra-rare disorders beyond PNH and aHUS. 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 potential health and medical benefits of Soliris® (eculizumab) for the 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, 2012, 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.||Hill A, Kelly R, Kulasekararaj A, et al. Eculizumab in paroxysmal nocturnal hemoglobinuria (PNH): a report of all 153 patients treated in the UK. Presented at the 54th Annual Meeting of the American Society of Hematology (ASH), Atlanta, GA, December 10, 2012: Abstract 3472.|
|2.||Szer J, Muus P, Roth A, et al. Long-term safety of sustained eculizumab treatment in patients with paroxysmal nocturnal hemoglobinuria. Presented at the 54th Annual Meeting of the American Society of Hematology (ASH), Atlanta, GA, December 8, 2012: Abstract 1260.|
|3.||Socié G, Schrezenmeier H, Muus P, et al. Eculizumab protects against TE and prolongs survival in patients with paroxysmal nocturnal hemoglobinuria: an International PNH Registry study. Presented at the 54th Annual Meeting of the American Society of Hematology (ASH), Atlanta, GA, December 10, 2012: Abstract 3480.|
|4.||Lee JW, Jang JH, Kim JS, et al. Risk of thromboembolism in patients with paroxysmal nocturnal hemoglobinuria presenting with both clinical symptoms and elevated hemolysis. Presented at the 54th Annual Meeting of the American Society of Hematology (ASH), Atlanta, GA, December 8, 2012: Abstract 1273.|
|5.||Nishimura J, Yamamoto M, Hayashi S, et al. A rare genetic polymorphism in C5 confers poor response to the anti-C5 monoclonal antibody eculizumab by nine Japanese patients with PNH. Presented at the 54th Annual Meeting of the American Society of Hematology (ASH), Atlanta, GA, December 10, 2012: Abstract 3197.|
|6.||Licht C, Muus P, Legendre C, et al. Eculizumab (ECU) safety and efficacy in atypical hemolytic uremic syndrome (aHUS) patients with long disease duration and chronic kidney disease: 2-year results. Presented at the 54th Annual Meeting of the American Society of Hematology (ASH), Atlanta, GA, December 8, 2012: Abstract 985.|
|7.||Greenbaum L, Legendre C, Babu S, et al. Eculizumab (ECU) in atypical hemolytic uremic syndrome (aHUS) patients with progressing thrombotic microangiopathy (TMA): 2-year data. Presented at the 54th Annual Meeting of the American Society of Hematology (ASH), Atlanta, GA, December 9, 2012: Abstract 2084.|
|8.||Hillmen P, Lewis SM, Bessler M, Luzzatto L, Dacie JV. Natural history of paroxysmal nocturnal hemoglobinuria. N Engl J Med. 1995;333:1253-1258.|
|9.||Kelly RJ, Hill A, Arnold LM, et al. Long-term treatment with eculizumab in paroxysmal nocturnal hemoglobinuria: sustained efficacy and improved survival. Blood. 2011;117(25):6786-6792.|
|10.||Dr. Anita Hill receives research support from Alexion Pharmaceuticals, Inc. and has served on advisory boards for the company.|
|11.||Dr. Jeffrey Szer has no relevant conflicts of interest to disclose.|
|12.||Dr. Gerard Socié has no relevant conflicts of interest to disclose.|
|13.||Movalia MK, Illingworth A. Distribution of PNH clone sizes within high risk diagnostic categories among 481 PNH positive patients identified by high sensitivity flow cytometry. Presented at the 54th Annual Meeting of the American Society of Hematology (ASH), Atlanta, GA, December 8, 2012: Abstract 1271.|
|14.||Two-year data show long-term benefits of chronic Soliris® therapy in patients with aHUS (press release). Alexion Pharmaceuticals, Inc.: November 3, 2012. http://news.alexionpharma.com/press-release/product-news/two-year-data-show-long-term-benefits-chronic-soliris-therapy-patients-ah.|
|15.||Dr. Larry Greenbaum receives research support from Alexion Pharmaceuticals, Inc. and is a consultant to the company.|
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