Keryx Biopharmaceuticals, Inc. 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 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 appears to have an acceptable safety and tolerability profile at the 2, 4, and 6g/day dose. The optimum dose of Zerenex in this study was 6g/day at which dose it appeared to be efficacious, safe and well tolerated as treatment for hyperphosphatemia in haemodialysis patients." Additionally, the investigators found that "Zerenex therapy for up to 28 days had no statistically significant effect on serum iron, ferritin, transferrin saturation, or total iron binding capacity."
The phase 2 study was designed to determine the safety and efficacy of several doses of Zerenex in patients with end stage renal disease who were undergoing haemodialysis. In this study, each of three Zerenex 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 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.
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). 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).
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 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 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."
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)
Keryx in-licensed the rights to Zerenex 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).