NEW YORK, June 18 /PRNewswire-FirstCall/ -- Keryx Biopharmaceuticals reported today the randomization of the last patient in its pivotal Phase 3 clinical trial of Sulonex(TM) (sulodexide oral gelcap), the Company’s lead drug candidate, for the treatment of diabetic nephropathy. This Phase 3 clinical program, with a total of 1,057 randomized patients worldwide, is being conducted under the Subpart-H guidelines for accelerated approval pursuant to a Special Protocol Assessment (SPA) with the Food and Drug Administration (FDA). Based on the completion of randomization, the Company expects to have the last patient complete the six months of active treatment before the end of the year.
The Phase 3 clinical program is a multi-center, randomized, double-blind, placebo-controlled study, comparing 200 mg daily of Sulonex(TM) versus placebo, with a 1:1 randomization between the two arms. The objective of this study is to determine the safety and efficacy of sulodexide in the treatment of patients with type 2 diabetes and persistent microalbuminuria, or diabetic nephropathy, despite being treated with a maximum approved or tolerated dose of an angiotensin II receptor blocker (ARB) or angiotensin-converting enzyme inhibitor (ACEi). The study is designed for patients to be on treatment for six months, followed by two months of evaluation off-treatment. During the treatment and off-treatment evaluation period, all patients in the study population are expected to continue to receive maximum approved or tolerated doses of ACEis or ARBs. Patients who were not already on maximum approved or tolerated doses of ACEis or ARBs for 120 days were required to go into a run- in period prior to randomization of up to 120 days. This run-in period was designed to stabilize blood pressure and to confirm persistent microalbuminuria while the patients are treated with maximum approved or tolerated doses of ACEis or ARBs.
The primary endpoint for this Phase 3 clinical trial is “therapeutic success” at 6 months, where therapeutic success is defined as (i) conversion from microalbuminuria to normoalbuminuria, as measured by albumin/creatinine ratio (ACR), with at least a 25% reduction in ACR relative to baseline ACR, or (ii) a 50% reduction in ACR relative to baseline ACR.
Concurrently with this Phase 3 clinical trial, the Company is continuing enrollment into its Phase 4 clinical trial, which is a randomized, double- blind, placebo-controlled study, also comparing 200 mg daily of Sulonex(TM) versus placebo, with a 1:1 randomization between the two arms. The objective of this Phase 4 study is to determine the efficacy of Sulonex(TM) in reducing the rate of progression to End-stage renal disease and adverse clinical sequelae in patients with type 2 diabetes and macroalbuminuria or overt diabetic nephropathy, despite being treated with a maximum approved or tolerated dose of an ARB. All patients in the Phase 4 study population are expected to continue to receive maximum approved or tolerated doses of ARBs during the course of the study. The Phase 4 study is designed to enroll approximately 2,200 patients.
The Company has committed to the FDA, as a condition to the approval of Sulonex based on the Phase 3 clinical trial under the guidelines of accelerated approval, that the Phase 4 study would be substantially enrolled at the time of the filing of the NDA for Sulonex. The Company believes they are on track to meet their commitment with approximately 40% of the required patients already randomized.
“We are very excited to have reached this significant milestone in the development of Sulonex(TM) and we are grateful for the tremendous dedication, support and guidance of the Collaborative Study Group and all the CSG investigators worldwide who dedicated themselves to completing this study in a timely-fashion for the potential benefit of their patients,” stated Michael S. Weiss, Chairman & CEO of Keryx. Weiss added, “We eagerly await the outcome of this international Phase 3 clinical trial.”
Edmund J. Lewis, MD, commented, “This is the largest trial ever conducted in patients with microalbuminuria and we are pleased that the Collaborative Study Group could once again lead the development of a novel agent for this disease. Randomizing this many patients in this timeframe is testament to the dedication and quality of our CSG investigators. All of us at the CSG are optimistic about the prospects of Sulonex and are eager to have this new drug available to treat our patients.”
The Sulonex phase 3 and Phase 4 program is being conducted by The Collaborative Study Group (CSG), the world’s largest standing renal clinical trial group, whose execution of the angiotensin-converting enzyme (ACE) inhibition trial of captopril in Type 1 diabetic nephropathy and the angiotensin II receptor blocker (ARB) trial of irbesartan in Type 2 diabetic nephropathy (I.D.N.T. study) both led to FDA approval and the recommendation of these agents as standards of care by the American Diabetes Association.
The lead investigator for these studies is Dr. Edmund J. Lewis, Director of Nephrology at the Rush-Presbyterian-St. Luke’s Medical Center in Chicago and Co-Chairman of the CSG. In North America, the principal-investigators are Dr. Larry Hunsicker, Professor of Medicine at the University of Iowa College of Medicine and Co-Chairman of the CSG, and Dr. Julia Lewis, Professor of Medicine at Vanderbilt University and a leading member of the CSG.
In Europe, the principal investigators are Dr. Dick de Zeeuw, Professor and Head of the Department of Clinical Pharmacology at the University Medical Center in Groningen, the Netherlands, and Dr. Itamar Raz, Professor of Medicine and Head of the Diabetes Center at the Hadassah Hebrew University Hospital in Jerusalem, Israel. Dr. de Zeeuw served as one of the lead investigators in the pivotal Phase 3 study for losartan, an ARB, in Type 2 diabetic nephropathy (R.E.N.A.A.L. study), which led to FDA approval of losartan. Dr. Raz played a major role as co-principal investigator in the I.D.N.T. study. Captopril, irbesartan and losartan are the only three drugs approved for the treatment of diabetic nephropathy.
The Asian-Pacific principal investigator is Dr. Robert Atkins, Professor of Medicine, Director of Nephrology at Monash University, in Melbourne, Australia. Dr. Atkins also played a major role, as co-principal investigator, in the I.D.N.T. study.
ABOUT THE SPA PROCESS AND SUBPART-H GUIDELINES
The SPA process is a procedure by which the FDA provides official evaluation and written guidance on the design and size of proposed protocols that are intended to form the basis for a new drug application (NDA). Subpart- H guidelines allow for the use of surrogate endpoints in pivotal Phase 3 trials to support NDA approval, with confirmatory studies completed post- approval.
In March of 2005, Keryx announced that it had finalized a SPA agreement with the FDA for the Phase 3 and Phase 4 clinical trials of Sulonex(TM). The clinical plan to support an NDA approval for Sulonex(TM) under Subpart H (accelerated approval), as agreed upon with the FDA under an SPA, consists of: (i) a single Phase 3 trial in patients with microalbuminuria based on the surrogate marker of regression of microalbuminuria as the primary endpoint; (ii) supportive data from previously conducted clinical studies; and (iii)
substantial recruitment into our Phase 4 confirmatory study that will measure clinical outcomes in patients with overt nephropathy, or macroalbuminuria.
ABOUT SULONEX(TM)
Sulonex (sulodexide oral gelcap) belongs to a proposed new class of nephroprotective, or kidney protecting, drugs, known as the glycosaminoglycans. A variety of members of this chemical family have been shown to decrease pathological albumin excretion in diabetic nephropathy in humans. Some of the members of this chemical family include the following approved drugs: standard heparin, low molecular weight heparin and danaparoid. These agents all require therapy by injection and are all potent anticoagulants, which are blood thinners capable of inducing bleeding. Sulonex, on the other hand, is given orally and, in this form, has demonstrated little, if any, anticoagulant effects to date.
Keryx owns the exclusive rights to use Sulonex(TM) for the treatment of diabetic nephropathy in North America, Japan and certain other markets outside of Europe. Diabetic nephropathy is a long-term complication of diabetes in which the kidneys are progressively damaged. Sulonex is a glycosaminoglycan compound with structural similarities to the broad family of marketed heparins and low molecular weight heparins. This drug has been marketed in a number of European, Asian and South American countries for many years by our licensor for certain cardiovascular conditions and has an established safety profile at the doses used for such indications. Additionally, it has been demonstrated in multiple clinical trials conducted in Europe and the U.S., including two randomized, double-blind, placebo-controlled Phase II studies, that Sulonex can reduce urinary protein excretion in patients with diabetic nephropathy.
Sulonex is in a pivotal Phase 3 and Phase 4 clinical program under a Special Protocol Assessment, or SPA, with the Food & Drug Administration, or FDA. These trials are being conducted by the Collaborative Study Group, or the CSG, the world’s largest standing renal clinical trials group.
ABOUT DIABETIC NEPHROPATHY
According to the American Diabetes Association, or the ADA, there are 20.8 million people in the United States (approximately 7% of the population) who have diabetes. Of this population, approximately 14.6 million have been diagnosed with diabetes, of whom approximately 90-95% have been diagnosed with Type II diabetes. Type 2 diabetes results from the combination of insulin deficiency and the body’s relative insensitivity to the insulin present, as opposed to Type 1 diabetes, in which severe insulin deficiency results from destruction of the insulin-producing beta cells of the pancreas. Moreover, the ADA estimates that approximately 40% of all diabetics in the United States, or approximately eight million people, have diabetic nephropathy. Diabetes is the most common cause of ESRD in the United States and in many other developed nations, and represents approximately 45% of all new cases of ESRD in the United States. Despite advances in clinical care, including improvements in glycemic or blood sugar control and blood pressure control, the number of Type 1 and Type 2 diabetes-related cases of ESRD continues to rise. In particular, the incidence of Type II diabetes-related ESRD is rapidly increasing. Approximately 20% of diabetics on dialysis in the United States survive for five years, making the mortality of end-stage renal failure in this group higher than most forms of cancer. Unfortunately, renal transplantation is an option for less than 15% of diabetics with ESRD, as compared to 35-40% of non- diabetics, principally due to age and concomitant vascular disease. Despite recent advances, diabetic nephropathy remains a potentially catastrophic illness for which partial but insufficient treatment is currently available.
ABOUT THE COLLABORATIVE STUDY GROUP
The Collaborative Study Group (CSG), the largest standing renal clinical trials group worldwide, is comprised of academic and tertiary care physician- researchers interested in collaborative clinical trials investigating new therapeutic approaches in the treatment of kidney disease. Since 1979, the CSG has conducted multiple large-scale clinical trials resulting in over 40 major publications in peer-reviewed journals. The CSG conducted pivotal trials of ACE Inhibition in Type 1 Diabetic Nephropathy and of Irbesartan in Type 2 Diabetic Nephropathy (I.D.N.T.), both of which led to FDA product registration for new indications and the recommendation of these agents as standard of care by the American Diabetes Association. The results of each of the CSG’s last three major clinical trials were published in the New England Journal of Medicine. The IDNT multi-national trial in collaboration with Bristol-Myers Squibb and Sanofi-Synthelabo is the largest trial in renal disease to date, consisting of 1,715 patients from 210 investigative sites worldwide. The CSG is currently conducting the pivotal clinical program for Sulonex(TM), including both the Phase 3 and Phase 4 studies.
ABOUT KERYX BIOPHARMACEUTICALS, INC.
Keryx Biopharmaceuticals is focused on the acquisition, development and commercialization of medically important, novel pharmaceutical products for the treatment of life-threatening diseases, including diabetes and cancer. Our lead compound under development is Sulonex(TM) (sulodexide), which we previously referred to as KRX-101, a first-in-class, oral heparinoid compound for the treatment of diabetic nephropathy, a life-threatening kidney disease caused by diabetes. Sulonex is in a pivotal Phase 3 and Phase 4 clinical program under a Special Protocol Assessment, or SPA, with the Food & Drug Administration, or FDA. Additionally, we are developing Zerenex(TM), an oral, inorganic, iron-based compound that has the capacity to bind to phosphorous and form non-absorbable complexes. Zerenex is currently in Phase II clinical development for the treatment of hyperphosphatemia (elevated phosphate levels) in patients with end-stage renal disease, or ESRD. We are also developing clinical-stage oncology compounds, including KRX-0401, a novel, first-in- class, oral anti-cancer agent that modulates Akt, a protein in the body associated with tumor survival and growth, and a number of other key signal transduction pathways, including the JNK and MAPK pathways, which are pathways associated with programmed cell death, cell growth, cell differentiation and cell survival. KRX-0401 is currently in Phase 2 clinical development for multiple tumor types. We also have an active in-licensing and acquisition program designed to identify and acquire additional drug candidates. Keryx is headquartered in New York City.
Cautionary Statement
Some of the statements included in this press release, particularly those anticipating future performance, future results from the Phase 3 and Phase 4 clinical trials, timelines for the completion of the Sulonex(TM) pivotal clinical trial program, including the Phase 3 and the Phase 4 clinical trials, the number of patients and clinical sites included in the Phase 3 and Phase 4 clinical trials, expectations regarding FDA approval and commercial launch of Sulonex(TM), market size estimates for Sulonex(TM), growth and operating strategies and similar matters, are forward-looking statements that involve a number of risks and uncertainties. For those statements, we claim the protection of the safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995. Important factors may cause our actual results to differ materially, including: our ability to successfully complete the Sulonex(TM) pivotal clinical program on a cost- effective basis; failure to meet the endpoints of the Phase 3 or Phase 4 studies; and other risk factors identified from time to time in our SEC reports, including, but not limited to, the report on Form 10-K for the year ended December 31, 2006, and our quarterly report on Form 10-Q for the quarter ended March 31, 2007. Any forward-looking statements set forth in this news release speak only as of the date of this news release. We do not intend to update any of these forward-looking statements to reflect events or circumstances that occur after the date hereof. This press release and prior releases are available at http://www.keryx.com/. The information in Keryx’s website is not incorporated by reference into this press release and is included as an inactive textual reference only.
Keryx Biopharmaceuticals, Inc.
CONTACT: Ronald C. Renaud Jr., Chief Financial Officer, Treasurer of KeryxBiopharmaceuticals, Inc., +1-212-531-5965
Web site: http://www.keryx.com//
