Paroxysmal nocturnal hemoglobinuria

- Leeds Teaching Hospital, NIH, and Alexion Pharmaceuticals Find Potential Link Between Red Blood Cell Destruction and Pulmonary Hypertension in PNH -

- Results Presented at American Society of Hematology Meeting -

CHESHIRE, Conn., Dec. 12 /PRNewswire-FirstCall/ -- Researchers from the Leeds Teaching Hospital NHS Trust, Leeds, UK; the National Heart, Lung and Blood Institute of the National Institutes of Health; and Alexion Pharmaceuticals, Inc. have shown for the first time that pulmonary arterial hypertension (PHT) may be a common condition in patients suffering from paroxysmal nocturnal hemoglobinuria (PNH). Pulmonary hypertension was observed in 50 percent of the hemolytic patients in a 28 PNH-patient descriptive study presented on Saturday, December 10th at the 47th Annual American Society of Hematology Meeting and Exposition in Atlanta. The results of this study also showed that nitric oxide, a key naturally occurring chemical in the body that normally lowers blood pressure, was diminished in blood from PNH patients in the descriptive study as compared to normal individuals, suggesting a potential mechanism for the presence of PHT in these patients.

Pulmonary hypertension is high blood pressure in the arteries that supply blood to the lungs. In this condition, the blood vessels narrow and their walls thicken, reducing the amount of blood they can carry. The narrowing causes blood pressure in the lungs to increase and forces the heart to work harder. Patients become tired, dizzy and short of breath (dyspneic), particularly during exertion. Patients with PNH -- a blood disorder characterized by the onset of severe hemolytic anemia, chronic fatigue and intermittent episodes of dark colored urine, known as hemoglobinuria -- frequently suffer from shortness of breath.

"The results of this study should raise the sensitivity of physicians to the possibility of pulmonary hypertension as a potential cause of morbidity in patients with PNH," said Peter Hillmen, M.B. Ch.B., Ph.D., Consultant Haematologist of The General Infirmary at Leeds, Leeds, UK, and lead investigator of the study. "PNH patients frequently have symptoms consistent with both anemia and pulmonary hypertension, including fatigue and dyspnea upon exertion."

The study results showed that 14 of 28 (or 50 percent) of these hemolytic PNH patients demonstrated pulmonary hypertension (PHT) as defined by echocardiographic examination with a tricuspid regurgitant jet velocity (TRV) of 2.5 m/sec or greater, with two patients showing moderate/severe PHT with TRVs of 3.5 and 3.8 m/sec. In addition, the results showed that plasma from 28 PNH patients consumed nitric oxide (mean consumption 34.6 +/- 8.3 uM) while plasma from nine normal volunteers did not (mean consumption 2.12 +/- 0.6 uM; p < 0.0001). In the 28 patient descriptive study, the ability of patient plasma to deplete nitric oxide showed a highly significant correlation with the degree of hemolysis as measured by levels of lactate dehydrogenase (R = 0.63; p = 0.0002).

In a different analysis presented by the researchers, nitric oxide consumption in these 28 PNH patients was compared to the nitric oxide consumption in a cohort of seven PNH patients who had been treated with eculizumab, an investigational monoclonal antibody drug that blocks the terminal complement part of the immune system (patients in study presented in ASH 2005 Abstract #1074). The complement cascade has been implicated in the destruction of red blood cells, or hemolysis, in PNH patients, as PNH blood cells are deficient in natural inhibitors of complement. In this separate seven patient cohort of treated PNH patients who experienced a reduction in their hemolytic activity, nitric oxide consumption appeared lower (mean consumption 13.2 +/- 4.8 uM) than the nitric oxide consumption in the 28 patient descriptive study (mean consumption 34.6 +/- 8.3 uM).

The study was led by Dr. Peter Hillmen of Leeds Teaching Hospital, Leeds, UK; Dr. Mark Gladwin, Chief, Vascular Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health; and Dr. Russell Rother, Senior Vice President, Discovery Sciences, Alexion Pharmaceuticals, Inc.

"Scientists from several institutions have brought together their multidisciplinary talents to suggest a surprisingly increased prevalence of a potentially serious medical condition, pulmonary arterial hypertension, in a rare, but severe blood disease, paroxysmal nocturnal hemoglobinuria," said Leonard Bell, M.D., Chief Executive Officer of Alexion. "As we look to conclude our global Phase III pivotal trial with eculizumab in PNH patients, we remain committed to further increasing the scientific and clinical communities' knowledge and awareness of the severe complications of PNH in order to eventually provide better and needed care to thousands of afflicted patients."

There currently is no drug specifically available for treatment of patients with PNH. Estimates suggest that approximately 2,000 - 10,000 people in the U.S., and a similar number in Europe, suffer from this disease.

Alexion is engaged in the discovery and development of therapeutic products aimed at treating patients with a wide array of severe disease states, including hematologic and cardiovascular disorders, autoimmune diseases and cancer. Alexion's two lead product candidates, pexelizumab and eculizumab, are currently undergoing evaluation in several clinical development programs, including two Phase III trials of eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria (PNH). Under the Special Protocol Assessment (SPA) process, the FDA has agreed to the design of protocols for the two trials of eculizumab in PNH patients that could, if successful, serve as the primary basis of review for approval of a licensing application for eculizumab in the PNH indication. Eculizumab has also been studied in rheumatoid arthritis and membranous nephritis. The Company's Phase III trial of pexelizumab in coronary artery bypass graft (CABG) surgery patients undergoing cardiopulmonary bypass (CPB) failed to achieve its primary endpoint, and the Company is assessing the impact of the results of this study, known as PRIMO-CABG2, on its ongoing Phase III trial of pexelizumab in acute myocardial infarction (AMI) patients. The pexelizumab trials are conducted in collaboration with Procter and Gamble Pharmaceuticals. Under the SPA process, the FDA has agreed to the design of protocols for the Phase III pexelizumab trials that could, if successful, serve as the primary basis of review for approval of licensing applications for the two indications. Preliminary results from the PRIMO-CABG2 trial of pexelizumab indicate that the trial is unlikely to support filing for licensing approval of pexelizumab in the CABG indication. Alexion is engaged in discovering and developing a pipeline of additional antibody therapeutics targeting severe unmet medical needs, through its wholly owned subsidiary, Alexion Antibody Technologies, Inc. This press release and further information about Alexion Pharmaceuticals, Inc. can be found at: http:/www.alexionpharm.com.

This news release contains forward-looking statements, including statements related to timing of announcement of clinical trial results and the progression of Alexion's drug candidates towards commercial sales. Forward- looking statements are subject to factors that may cause Alexion's results and plans to differ from those expected, including the results of pre-clinical or clinical studies (including termination or delay in clinical programs), the need for additional research and testing, decision of the FDA not to approve (or to materially limit) marketing of one or both of Alexion's two drug candidates, delays in arranging satisfactory manufacturing capability, inability to acquire funding on timely and satisfactory terms, delays in developing or adverse changes in commercial relationships, the possibility that results of earlier clinical trials are not predictive of safety and efficacy results in later clinical trials, dependence on Procter & Gamble Pharmaceuticals for development and commercialization of pexelizumab, the risk that third parties won't agree to license any necessary intellectual property to us on reasonable terms, 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 Annual Report on Form 10-K for the year ended July 31, 2005 and in our other filings with the Securities and Exchange Commission. P&GP retains the development rights and the termination rights discussed in Alexion's Form 10-K referred to above. 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.

CONTACT: Leonard Bell, M.D., Chief Executive Officer, Alexion Pharmaceuticals, Inc., +1-203-272-2596; Patricia Garrison (Scientific Media), +1-917-322-2567, or Rhonda Chiger (Investors), +1-917-322-2569, both of Rx Communications; Robert Stanislaro (Business and Financial Media), Noonan/Russo, +1-212-845-4268

Web site: http:/www.alexionpharm.com

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