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Alexion Completes Randomization of Its Phase III Pivotal TRIUMPH Efficacy Trial of Eculizumab in PNH Patients

Posted on: Monday, 18 July 2005, 06:00 CDT

CHESHIRE, Conn., July 18 /PRNewswire-FirstCall/ -- Alexion Pharmaceuticals, Inc. announced today that it has completed randomization of the pivotal Phase III TRIUMPH efficacy trial of eculizumab in patients with the chronic orphan blood disorder Paroxysmal Nocturnal Hemoglobinuria ("PNH"). In accordance with the trial's design, enrolled patients first entered a screening phase of up to three months to confirm their eligibility to be included in the trial, and were then randomized to receive either eculizumab or placebo in a six month treatment phase. Eculizumab is a monoclonal antibody drug that blocks the terminal complement part of the immune system. There currently is no drug specifically available for treatment of patients with PNH, whose blood cells are deficient in natural inhibitors of terminal complement.

Approximately 85 PNH patients were randomized into the six month treatment phase, which exceeds the patient requirements agreed upon with the U.S. Food and Drug Administration as part of the Special Protocol Assessment (SPA) for TRIUMPH. Having completed randomization, it is anticipated that the final patient will complete the six month treatment phase near the end of this year.

"We are pleased to have met our objective of randomizing the last patient in the TRIUMPH trial, on target with our earlier announced schedule," said Leonard Bell, M.D., Chief Executive Officer of Alexion. "The enthusiastic response to TRIUMPH allowed us to increase the number of physicians and patients included in the study, while still maintaining our stated goal of completing the trial by the end of 2005 and expecting top line results in the first quarter of 2006. We remain focused on driving the PNH program forward to meet the needs of the severely underserved PNH patient population."

In addition to TRIUMPH, the pivotal Phase III clinical program includes the open-label, companion safety trial, SHEPHERD. The SHEPHERD protocol includes a six month interim analysis and a further six months of safety observations. Patients are currently being actively enrolled into SHEPHERD.

Eculizumab, an investigational drug therapy, has been granted Orphan Drug Status from both the U.S. and European regulatory agencies to treat PNH. 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 PNH. Estimates suggest that up to 2,000 - 10,000 people in the U.S., and a similar number in Europe, suffer from this disease.

About TRIUMPH and SHEPHERD

TRIUMPH is a double-blind, randomized, placebo-controlled multi-center pivotal Phase III trial, examining the effects of eculizumab on the co-primary endpoints of hemoglobin stabilization and blood transfusion requirement in hemolytic, transfusion-dependent PNH patients during six months of therapy. The study has enrolled patients in the US, Canada, Europe, and Australia. TRIUMPH is designed to be a single pivotal efficacy trial for eculizumab therapy in PNH. The companion trial, called SHEPHERD, is an open-label, non- randomized, non-placebo-controlled, multi-center clinical study, primarily aimed at generating additional safety data with eculizumab in a broader population of hemolytic PNH patients with a history of transfusion. SHEPHERD is expected to enroll approximately 75 patients in the US, Canada, Europe, and Australia.

The TRIUMPH trial marks the second study of eculizumab in PNH patients. Results of the first trial, a three-month, open-label study in 11 patients, reported in the February 5, 2004 issue of the New England Journal of Medicine showed that patients treated with eculizumab experienced a substantial decrease in the destruction of PNH red blood cells, with the mean percentage of these cells increasing from 36.7 percent of the total population found in the body to 59.2 percent (P=0.005), and lactate dehydrogenase (LDH) levels (a biochemical marker of red blood cell destruction) falling from a mean of 3,111 IU per liter to a mean of 594 IU per liter (P=0.002). This reduction in PNH red blood cell destruction helped reduce the median patient transfusion rates from 1.8 units per patient, per month, to 0.0 units per patient, per month (P=0.003). Episodes of hemoglobinuria (dark colored urine indicative of excessive red blood cell destruction) were reduced by an average of 96 percent (P<0.001) and quality of life measurements, using EORTC QLQ C-30, a standard questionnaire developed to assess quality of life in cancer patients particularly suffering from severe fatigue and anemia, substantially improved during treatment. In this trial, eculizumab appeared safe and well tolerated. Patients from the first trial have continued to receive treatment with eculizumab.

About PNH

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 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 therapy to help patients cope with the symptoms of anemia, as no drugs are currently approved to specifically treat PNH. It is estimated that between 2,000 and 10,000 people in the U.S. suffer from PNH, with similar numbers in Europe.

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 licensing applications for the two indications. Also 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 licensing application for eculizumab in the PNH indication. Eculizumab is also being studied 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, including statements regarding the timing of completion of the TRIUMPH and SHEPHERD trials. 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, 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.

Contacts: Alexion Pharmaceuticals, Inc. Rx Communications Leonard Bell, M.D. Patricia Garrison (Scientific Media) Chief Executive Officer (917) 322-2567 (203) 272-2596 Rhonda Chiger (Investors) (917) 322-2569 Noonan/Russo Emily Poe (Business and Financial Media) (212) 845-4266

Alexion Pharmaceuticals, Inc.

CONTACT: Leonard Bell, M.D., Chief Executive Officer, AlexionPharmaceuticals, Inc., +1-203-272-2596; Scientific Media - Patricia Garrison,+1-917-322-2567, or Investors - Rhonda Chiger, +1-917-322-2569, both of RxCommunications; Business and Financial Media, Emily Poe of Noonan-Russo,+1-212-845-4266, all for Alexion Pharmaceuticals, Inc.

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

Source: PRNewswire-FirstCall

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