NEW YORK, June 29 /PRNewswire-FirstCall/ -- Keryx Biopharmaceuticals, Inc. (Nasdaq: KERX - News) today announced positive final results from the Phase 2 multi- center study entitled: “A randomized, double-blind, placebo-controlled, dose ranging study of the effects of Zerenex(TM) on serum phosphate in patients with end stage renal disease (ESRD).” This Phase 2 study was conducted under an IND (Investigational New Drug) sponsored by the Company’s licensors in both the US and Taiwan.
From this Phase 2 Study, the investigators concluded that “Zerenex(TM) appears to have an acceptable safety and tolerability profile at the 2, 4, and 6g/day dose. The optimum dose of Zerenex(TM) in this study was 6g/day at which dose it appeared to be efficacious, safe and well tolerated as treatment for hyperphosphatemia in hemodialysis patients.” Additionally, the investigators found that “Zerenex(TM) therapy for up to 28 days had no statistically significant effect on serum iron, ferritin, transferrin saturation, or total iron binding capacity.”
Design of the Phase 2 Study
The Phase 2 study was designed to determine the safety and efficacy of several doses of Zerenex(TM) in patients with end stage renal disease who were undergoing hemodialysis. In this study, each of three Zerenex(TM) doses (2g, 4g and 6g) administered daily with meals was compared to placebo. Patients who had been on other phosphate binders prior to enrolling in this study underwent a 1-2-week washout period prior to randomization. Patients who had a serum phosphorous level greater than or equal to 5.5 mg/dl and less than or equal to 10 mg/dl by the end of this washout period were eligible to be randomized to one of four treatment groups at a ratio of 2:2:2:1, (Zerenex(TM) 2g, 4g, 6g and placebo, respectively) and were treated for 28 days. The primary endpoint for this study was the change in serum phosphorous concentration at day 28 relative to baseline.
Phase 2 Data Analysis
Of the 116 patients randomized in the study, 111 patients were evaluable for efficacy at 28 days and were included in the analysis.
At day 28, there was a statistically significant dose response to Zerenex in reducing serum phosphorous concentration (p=0.0073). In the 6g/day Zerenex group the mean decrease in serum phosphorous concentration was statistically significant when compared with placebo (p=0.0119)](see Table 1). There was also a statistically significant dose response to Zerenex in the calcium x phosphorous (Ca x P) product at day 28 (p=0.0158). In the 6g/day Zerenex group the mean decrease in Ca x P product when compared with placebo was statistically significant (p=0.0378) (See Table 2).
Table 1: Changes in Serum Phosphorous Concentration (mg/dL) on day 28 compared to day 0 (baseline) at Zerenex doses of 2, 4 and 6 g/day.
Placebo 2g/day 4g/day 6g/day (n=16) (n=31) (n=32) (n=32) Day 0 (Baseline)* 7.2 (1.4) 7.2 (1.2) 7.1 (1.3) 7.3 (1.3) Day 28 (End of Treatment Period)* 7.2 (1.2) 6.9 (2.2) 6.0 (1.3) 5.8 (1.8) Placebo Comparison: Mean Difference from Placebo -.02 -1.1 -1.5 P-value NS 0.06 0.0119 Baseline Comparison: Mean Difference from Baseline -0.1 -0.3 -1.1 -1.5 P-value NS NS NS <0.01 *mean (standard deviation)
Table 2: Changes in the Calcium x Phosphorous (mg/dL) on day 28 compared to day 0 (baseline) at Zerenex doses of 2, 4 and 6 g/day.
Placebo 2g/day 4g/day 6g/day (n=16) (n=31) (n=32) (n=32) Day 0 (Baseline)* 62.8 (13.9) 62.9 (13.2) 63.5 (10.7) 65.8 (12.2) Day 28 (End of Treatment Period)* 63.2 (12.6) 61.7 (21.3) 55.4 (13.4) 54.1 (17.7) Placebo Comparison: Mean Difference from Placebo -0.9 -7.91 -11.4 P-value .8950 0.1375 0.0378 Baseline Comparison: Mean Difference from Baseline -0.3 -1.1 -8.1 -11.7 P-value NS NS NS <0.01 *mean (standard deviation)
There were no deaths over the course of the 28-day study and there were no serious adverse events (SAEs) that were deemed by the investigators to be definitely related to Zerenex. The majority of adverse events were of mild severity. Seven (43.8%), 13 (39.4%), 9 (26.5%), and 14 (42.4%) patients in the placebo, 2, 4, and 6g treatment groups, respectively, experienced no adverse events more severe than mild and 1 (6.3%), 0 (0.0%), 2 (5.9%), 1 (3.0%), of the placebo, 2,4, and 6 grams per day groups, respectively, experienced at least one severe AE. Possibly or probably related AEs occurred in 4 (25.0%), 7 (21.2%), 8 (23.5%), and 7 (21.2%) of the placebo, 2, 4, and 6 grams per day groups, respectively.
Michael S. Weiss, Chairman and Chief Executive Officer of Keryx Biopharmaceuticals, Inc., stated, “We are pleased with the positive results from this dose-ranging study of Zerenex(TM) as it represent a potentially new opportunity for Keryx to help patients with kidney disease. Weiss added “Zerenex represents an important complementary product to our lead development compound, Sulonex(TM) and we are looking forward to reviewing these data with the Collaborative Study Group and other industry leaders in an effort to determine next steps and implement the next phase of clinical development.”
Stephen M. Korbet, MD, Associate Director of the Section of Nephrology at Rush University Medical Center, Chicago, IL and member of the Collaborative Study Group, commented, “The potential for treating hyperphosphatemia with a safe and effective iron-based compound is quite appealing given the long-term safety concerns associated with many of the currently available therapies which contain calcium, lanthanum or aluminum.”
ABOUT ZERENEX(TM)
Zerenex, an oral, inorganic, iron-based compound that has the capacity to bind phosphate and form non-absorbable complexes, is currently in Phase II clinical development for the treatment of hyperphosphatemia (elevated phosphorous levels) in patients with end-stage renal disease, or ESRD. The efficacy of Zerenex has been demonstrated in two previous Phase II clinical trials using single fixed dose regimens. In both studies, Zerenex was able to significantly reduce serum phosphorous (p <.005) (See Tables I and II).
Keryx in-licensed the rights to Zerenex(TM) from Panion & BF Biotech, Inc., a drug development company based in Taiwan. Panion holds a use patent (expiring 2020, including 3 years of expected patent term extension) and two manufacturing process patents (expiring 2023).
Table I: Effects on Serum Phosphorus at 4 weeks (n=28) Open Label, Randomized, Parallel Groups, 2 sites Serum Phosphorous Change from Baseline Baseline End-Point (mg/dL) (Four Weeks) (mg/dL) Zerenex(TM) (4.5g/day)* 7.2 (2.5) 5.9 (2.0) P<0.005 Calcium Acetate (PhosLo®) (4g/day) (1)* 7.2 (2.0) 5.6 (1.7) P<0.005 (1) Serum calcium increased significantly from baseline to end of treatment (8.7 +/- 0.5 mg/dL to 9.2 +/- 0.7 mg/dL) only in the calcium acetate group. *mean (standard deviation) Table II: Effects on Serum Phosphorus at 4 weeks (n=54) Open Label, Randomized, Crossover, 2 sites Serum Phosphorous Change from Baseline Baseline End-Point (mg/dL) (Four Weeks) (mg/dL) Zerenex(TM) (4.5g/day)* 6.7 (1.9) 5.7 (1.6) P<0.001 Calcium Carbonate (3g/day) (1)* 7.2 (1.9) 5.2 (1.5) P<0.001 (1) Serum calcium increased only in patients treated with calcium carbonate. *mean (standard deviation)
ABOUT HYPERPHOSPHATEMIA It is currently estimated that there are over 1 million people with end stage renal disease in major markets, and due to aging populations and the global diabetes epidemic, the number of ESRD patients is expected to almost double by 2010. Hyperphosphatemia, or elevated phosphate levels (as measured by serum phosphorus), develops in up to 80% of ESRD patients. The Kidney Disease Outcome Quality Initiative (K/DOQI) guidelines recommend serum phosphorus for patients undergoing maintenance dialysis should be maintained between 3.5 and 5.5 mg/dL. If not treated, hyperphosphatemia can result in soft tissue and vascular calcification, which in turn raises the risk of heart disease, stroke, bone disease and increased mortality.
Currently available treatments for hyperphosphatemia do not reliably achieve treatment goals set by kidney specialists. Additionally, there are safety concerns about the use of available products. Aluminum-based products accumulate and may cause bone disease, anemia and nerve damage. Calcium-based products may lead to hypercalcemia and soft tissue calcification. Polymer- based phosphate binders are contra-indicated in certain patients with bowel obstruction and may be associated with higher incidence of metabolic acidosis. As a result, a need remains for novel, more efficient, convenient and tolerable treatment options that lower phosphate without raising calcium levels or aluminum levels and which can avoid or ameliorate the other safety concerns associated with current treatment options.
ABOUT KERYX BIOPHARMACEUTICALS, INC.
Keryx Biopharmaceuticals, Inc. is focused on the acquisition, development and commercialization of novel pharmaceutical products for the treatment of life-threatening diseases, including diabetes and cancer. Keryx’s lead compound under development is Sulonex(TM), 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 III and Phase IV clinical program under a Special Protocol Assessment with the Food & Drug Administration. Additionally, Keryx is developing Zerenex(TM), an oral, inorganic, iron-based compound that has the capacity to bind phosphate and form non-absorbable complexes. Zerenex is currently in Phase II clinical development for the treatment of hyperphosphatemia (elevated serum phosphorous levels) in patients with end- stage renal disease. Keryx is also developing clinical-stage oncology compounds, including KRX-0401, a novel, first-in-class, oral modulator of Akt, a pathway associated with tumor survival and growth, and other important signal transduction pathways. KRX-0401 is currently in Phase II clinical development for multiple tumor types. Keryx also has 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 financial performance, business prospects and clinical results for Zerenex(TM), may be 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. Among the factors that could cause our actual results to differ materially are the following: inability to successfully and cost-effectively complete clinical trials for Zerenex(TM); inability to meet anticipated development timelines for Zerenex(TM) due to recruitment, clinical trial results, manufacturing capabilities or other factors; changing needs of the hyperphosphatemia market; competition from other compounds currently marketed and in development for the treatment of patients with hyperphosphatemia; and other risk factors identified from time to time in our reports filed with the Securities and Exchange Commissions. Any forward-looking statements set forth in this press release speak only as of the date of this press 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 our website is not incorporated by reference into this press release and is included as an inactive textual reference only.
Contact: Ronald C. Renaud, Jr. Chief Financial Officer 212 531-5965 rrenaud@keryx.com
Source: Keryx Biopharmaceuticals, Inc.
