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Alexion Pharmaceuticals Reports Two-Year Safety and Efficacy Data of Chronic Eculizumab Therapy in Patients With Paroxysmal Nocturnal Hemoglobinuria

Posted on: Tuesday, 7 December 2004, 06:00 CST

CHESHIRE, Conn., Dec. 7 /PRNewswire-FirstCall/ -- Alexion Pharmaceuticals, Inc. announced that the two-year cumulative results of an ongoing extension program of an initial pilot trial of eculizumab in patients with paroxysmal nocturnal hemoglobinuria (PNH) was presented last night at the 46th Annual American Society of Hematology Meeting and Exposition in San Diego. This 11 patient open-label extension study is being conducted in the United Kingdom at two sites and patients have now completed up to 26 months of chronic eculizumab therapy. These results showed that eculizumab administration for two years was associated with statistically significant reductions in hemolysis and in the need for blood transfusions, a key clinical objective of the trial.

Following the initial 12 week pilot trial (reported in the February 5, 2004 issue of the New England Journal of Medicine), all 11 patients chose to participate in two consecutive one year extension studies, one of which is still underway. The trial included both aplastic (poor bone marrow reserve resulting in low red blood cell production) and non-aplastic PNH patients. Maintenance doses of 900 mg eculizumab every 12-to-14 days were sufficient to completely and consistently block complement activity in all patients, as evidenced by the lack of hemolysis. The dramatic reduction in red blood cell destruction demonstrated in the pilot study was maintained throughout the extension phases as levels of lactate dehydrogenase decreased from a mean of 3111 +/- 598 during the 12 months before treatment to 634 +/- 34 following treatment for up to 26 months (p=0.002). This reduction in red blood cell destruction coincided with an increase in the survival of PNH red blood cells from 36.7% of the total red blood cell population to 58.9% (p=0.001). The protection of the PNH red blood cells led to a decrease in the mean and median transfusion rates from 2.1 and 1.8 units/patient/month during the 12 month period prior to eculizumab therapy to 0.4 and 0.3 units/patient/month (p<0.001), respectively, through the 23-26 month treatment period. Treatment with eculizumab alone, or in combination with erythropoeitin in aplastic patients, has rendered 7 of 11 patients transfusion independent for at least the last six months of the study. In addition, classical PNH symptoms attributed to hemoglobin release during red blood cell destruction including abdominal pain, dysphagia and erectile dysfunction have resolved or at least dramatically declined in all patients. Ten of the original 11 patients remain on eculizumab. Eculizumab continues to be well tolerated in these patients. The most commonly reported adverse events were flu-like symptoms, sore throat, headache, and upper respiratory infection. There have been four serious adverse events. No patients have discontinued treatment due to an adverse event. The adverse event profile for eculizumab-treated patients in this study is similar to that of placebo-treated patients in other patient population trials of eculizumab.

"We continue to be encouraged by the sustained effect of eculizumab in this ongoing clinical trial," said Peter Hillmen, M.B. Ch.B., Ph.D., Consultant Haematologist of The General Infirmary at Leeds, Leeds, UK, and lead investigator of the pilot study. "We are particularly encouraged by the apparent resolution of various classical PNH symptoms that are thought to be a consequence of excessive free hemoglobin in the blood stream during red blood cell destruction. Continued treatment of these patients in the extension program has also allowed us to investigate the use of erythropoeitin (a red blood cell production enhancer) in combination with eculizumab in patients with poor bone marrow reserve. By preventing complement-mediated destruction of red blood cells with eculizumab, while concomitantly driving production of these cells in these more aplastic patients, we appear to have been able to further reduce the need for blood transfusions. This observation will be further tested as more patients are treated in the ongoing Phase III program."

Alexion reported on November 1, 2004 that it had initiated the treatment phase of a pivotal Phase III efficacy trial with eculizumab in PNH patients called TRIUMPH. Alexion previously reached an agreement with the FDA on the design of TRIUMPH, and the companion safety trial called SHEPHERD, under the FDA's Special Protocol Assessment (SPA) process. It is expected that, if successful, the combined trials will complete the application that will serve as the primary basis of review for the approval of a Biologics License Application (BLA) for eculizumab in the PNH indication.

The TRIUMPH pivotal Phase III trial will examine the effects of eculizumab on the co-primary endpoints of hemoglobin stabilization and blood transfusion in hemolytic, transfusion-dependent PNH patients during six months of therapy. TRIUMPH is a double-blind, randomized, placebo-controlled multi-center clinical trial. The study is expected to enroll approximately 75 patients in the US, Canada, Europe and Australia. TRIUMPH is designed to be a single pivotal efficacy trial for eculizumab in PNH. Results of TRIUMPH are expected during the second half of 2005.

The companion safety trial, SHEPHERD, will be conducted to generate additional safety data with eculizumab in hemolytic PNH patients with a history of transfusion. SHEPHERD will be an open-label, non-placebo- controlled, multi-center clinical trial. The study is expected to enroll approximately 75 patients in the US, Canada, Europe and Australia. Alexion expects to initiate the SHEPHERD trial in the coming weeks.

"In a life-long disease, the observation of sustained and statistically significant clinical improvement with chronic treatment for two years is an important clinical milestone," noted Leonard Bell, M.D., Chief Executive Officer of Alexion. "Such sustained clinical outcomes are encouraging, particularly for patients suffering from this life-long disease. We are now focused on executing the ongoing Phase III pivotal PNH eculizumab program and efficiently completing development in order to meet the needs of the severely underserved PNH patient population."

If approved for PNH, eculizumab would represent the first approved drug from a new class of anti-inflammatory therapeutics -- terminal complement inhibitors -- as well as the first drug available specifically for patients suffering from this rare blood disease. In December 2003, Alexion announced that it had received orphan drug status for the use of eculizumab in PNH from both the FDA and the European Agency for the Evaluation of Medicinal Products.

PNH is a blood disorder characterized by the onset of severe anemia, chronic fatigue and intermittent episodes of dark colored urine, known as hemoglobinuria. PNH patients are also at increased risk of forming life- threatening blood clots, or thromboses, which are a leading cause of death (approximately 50%) in this disease. People with PNH have an acquired deficiency of proteins that normally protect red blood cells from a component of the body's natural defense system, known as the complement cascade. Lack of these complement inhibitor proteins leaves PNH red blood cells susceptible to destruction (hemolysis), which is manifest as a reduction in blood hemoglobin, causing patients to become anemic. In some cases, these patients are dependent on blood transfusions. Currently, physicians prescribe either steroids or other immunosuppressive drug therapies to help patients cope with the symptoms of anemia, as no drugs are currently approved to specifically treat PNH. Estimates suggest that up to 2,000 - 10,000 people in the U.S. suffer from this condition.

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), a Phase III trial of pexelizumab in coronary artery bypass graft (CABG) surgery patients undergoing cardiopulmonary bypass (CPB), and a 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 Special Protocol Assessment 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 Biologics License Applications for the two indications. Eculizumab has completed a pilot clinical trial for the treatment of paroxysmal nocturnal hemoglobinuria (PNH). Under the Special Protocol Assessment 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 Biologics License Application for eculizumab in the PNH indication. Eculizumab is also in Phase II clinical development in rheumatoid arthritis and membranous nephritis. 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 on the World Wide Web at: http://www.alexionpharm.com/.

This news release contains forward-looking statements. Such 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, 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, 2004 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:

Alexion Pharmaceuticals, Inc.

Leonard Bell, M.D.

Chief Executive Officer

(203) 272-2596

Euro RSCG Life NRP

Ernie Knewitz (Media)

(212) 845-4253

Rx Communications

Rhonda Chiger (Investors)

(917) 322-2569

Alexion Pharmaceuticals, Inc.

CONTACT: Leonard Bell, M.D., Chief Executive Officer of AlexionPharmaceuticals, Inc., +1-203-272-2596; or Ernie Knewitz (Media) of Euro RSCGLife NRP, +1-212-845-4253; or Rhonda Chiger (Investors) of Rx Communications,+1-917-322-2569

Web Site: http://www.alexionpharm.com/

Source: PRNewswire-FirstCall

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