Keryx Biopharmaceuticals, Inc. (Nasdaq: KERX) today announced positive top-line results from the Phase 3 short-term efficacy study component of its Phase 3 registration program of Zerenex™ (ferric citrate), the Company's ferric iron-based phosphate binder for the treatment of elevated serum phosphorus levels, or hyperphosphatemia, in patients with end-stage renal disease on dialysis. In this study, conducted pursuant to a Special Protocol Assessment (SPA) with the Food and Drug Administration (FDA), Zerenex met the study's primary endpoint, described below, demonstrating a highly statistically significant dose response. In addition, key secondary endpoints were also met with high statistical significance.
This Phase 3 study was a multicenter, randomized, open-label trial with a two-week washout period, following which patients were randomized 1:1:1 to receive a fixed dose of Zerenex of either 1 gram, 6 grams or 8 grams per day for a treatment period of 28 days. Zerenex was administered using a 1 gram oral caplet formulation, hence, the fixed-dose arms of 1 gram, 6 grams and 8 grams per day represent 1, 6 and 8 pills per day, respectively.
One hundred fifty-one dialysis patients were enrolled into the study. The Intent-to-Treat (ITT) group included 146 patients, representing all patients who took at least one dose of Zerenex and provided a Baseline (at the end of washout) and at least one post-Baseline efficacy assessment. Efficacy assessments were taken weekly starting at Baseline and subsequently at days 7, 14, 21 and 28.
EFFICACY DATA ANALYSES
The primary endpoint of the study was to determine whether there is a dose response in the change in serum phosphorus from Baseline to Day 28 in the ITT group, using a regression analysis to evaluate this objective.
The study met the primary endpoint, with the regression analysis indicating a highly statistically significant dose response (p<0.0001).
Additional efficacy results are as follows:
In addition, a statistically significant dose response increase in serum bicarbonate was observed in the study, indicating the potential ability of Zerenex to manage metabolic acidosis, as seen in prior clinical studies with Zerenex. Metabolic acidosis is a condition that occurs in many dialysis patients when the kidneys do not remove sufficient acid from the body, leading to low blood pH. The consequences of metabolic acidosis can be severe, including coma and death. The inability to manage metabolic acidosis is believed to be a drawback for some of the currently marketed phosphate binders.
Importantly, and as anticipated, no clinically meaningful change in serum calcium was observed in the study. Additionally, a statistically significant dose response reduction in calcium-phosphorus product was also observed in the study. Elevated levels of serum calcium (hypercalcemia) and high levels of calcium-phosphorus product, both of which are believed to be drawbacks from the use of some of the currently marketed phosphate binders, increase the risk of soft tissue calcification and may contribute to the substantial morbidity and mortality seen in patients with end-stage renal disease.
Certain iron parameters, including ferritin and TSAT, were measured in the study. Modest upward trends in ferritin and TSAT levels were observed in the 6 grams/day and 8 grams/day dose groups, which further support the Company's belief that Zerenex has the potential to reduce the need for intravenous (IV) iron supplements and/or erythropoiesis-stimulating agents (ESAs) in dialysis patients. IV iron and ESA use is being evaluated in the ongoing Phase 3 long-term study. If reductions in use are confirmed, the Company believes this additional benefit would significantly expand Zerenex's market potential.
Zerenex appeared to be safe and well-tolerated in the study, with only nine patients (6%) in the ITT group dropping out of the study, which further supports Zerenex's favorable safety profile seen in prior clinical trials.
The full efficacy and safety data from the study is expected to be presented at a future medical conference.
Dr. Julia Lewis, Professor of Medicine, Department of Nephrology, Vanderbilt University School of Medicine, member of the Executive Committee of the Collaborative Study Group and Study Chair of the Zerenex Phase 3 registration program, commented, "This is a very important day for all of us involved in the Zerenex program. Based on the results of this Phase 3 study, it appears that the Zerenex efficacy and safety profile is emerging in a way that could make it the phosphate binder of choice for dialysis patients." Dr. Lewis continued, "We are very excited to have taken this step forward towards bringing Zerenex to the patients who are in need of additional alternatives to the existing phosphate binders."
Ron Bentsur, Chief Executive Officer of Keryx, stated, "The successful completion of this Phase 3 study is perhaps the most important milestone in Keryx's history. We are excited to be announcing these robust results which demonstrate Zerenex's potential benefits over the currently marketed phosphate binders, including advantages in pill burden, safety and compliance. We believe that the data presented today and the overall profile of Zerenex position the drug candidate to potentially become market leader in this $1.5 billion, rapidly growing market." Mr. Bentsur continued, "We sincerely thank the study investigators and coordinators, and we are particularly grateful to the Collaborative Study Group, whose expertise, guidance and dedication have been extraordinary."
Keryx Biopharmaceuticals, Inc.