New York, NY - July 24, 2014 -- Keryx Biopharmaceuticals, Inc. (Nasdaq:KERX) (the "Company") announced the publication of results from the long-term, randomized, active control Phase 3 study of Zerenex (ferric citrate), the Company's investigational oral ferric iron-based phosphate binder, for the treatment of hyperphosphatemia in patients with end-stage renal disease (ESRD) on dialysis. The PERFECTED study (PhosphatE binding and iRon delivery with FErric CiTrate in EsrD) was published online today in the Journal of the American Society of Nephrology (JASN).
This Phase 3 study was a multicenter, randomized, open-label trial in 441 ESRD patients on hemodialysis or peritoneal dialysis designed to determine the safety and efficacy of Zerenex as a treatment to reduce serum phosphorus as well as raise iron stores and reduce intravenous (IV) iron and erythropoietin-stimulating agents (ESA) usage.
Zerenex met the study's primary end-point demonstrating a highly statistically significant change in serum phosphorus versus placebo over the four-week Placebo Control Period. Using a sequential gatekeeping strategy for the key pre-defined secondary end-points, Zerenex also demonstrated statistically significant increases in serum ferritin and transferrin saturation (TSAT), and significant reductions in the use of IV iron and ESAs, versus an active control of Renvela® (sevelamer carbonate) and/or Phoslo® (calcium acetate) over the 52-week Active Control Period of the study. In addition, mean hemoglobin levels were higher in subjects treated with Zerenex as compared to subjects treated with active control.
"Zerenex effectively reduces serum phosphorus levels within the KDOQI range (3.5 mg/dL to 5.5 mg/dL) while having the additional patient benefits of increasing iron stores and decreasing the need for IV iron and ESAs, while maintaining hemoglobin levels," said Julia Lewis, MD, lead investigator, nephrologist and Professor of Medicine at Vanderbilt University Medical Center. "If approved, the combined benefits of Zerenex would be of value for patients, health care professionals and the healthcare system."
The Company's New Drug Application (NDA) for Zerenex is currently under review by the U.S. Food and Drug Administration (FDA).
Ron Bentsur, Chief Executive Officer of Keryx, commented, "We are very pleased with the publication of the Phase 3 PERFECTED study results in a premier peer-reviewed nephrology journal and are encouraged by Zerenex's potential differentiated product profile." Mr. Bentsur added, "We thank the investigators and patients who participated in this study and look forward to potentially bringing Zerenex to market in the U.S."
Phosphorus Control is Necessary for Most ESRD Patients on Dialysis
In the United States, according to data from the U.S. Renal Data System, there are currently approximately 600,000 ESRD patients, with the number of ESRD patients projected to rise in the future. The majority of ESRD patients in the United States, more than 400,000, require dialysis. Phosphate retention and the resulting hyperphosphatemia in patients with ESRD on dialysis are associated with secondary hyperparathyroidism, renal osteodystrophy, soft tissue mineralization and an increase in adverse cardiovascular events. Hyperphosphatemia is ubiquitous in ESRD, with the majority of the patients requiring chronic treatment with phosphate-binding agents to lower and maintain serum phosphorus at acceptable levels.
Zerenex Administration Over 52 Weeks Increased Iron Stores
In addition, approximately seventy percent of dialysis patients are truly or functionally iron depleted, suffer from anemia and require treatment with IV iron and/or ESA injections. The newly published clinical trial results show that, in addition to its efficacy as a phosphate binder, Zerenex also significantly raises iron stores as measured by serum ferritin and TSAT.
The results showed Zerenex demonstrated a statistically significant treatment difference versus the active control group in mean change in serum ferritin (+306 ng/mL vs. +19 ng/mL) and TSAT (+8% vs -1.2%) from baseline (day 0) to week 52. In the PERFECTED study, subjects randomized to receive Zerenex required significantly lower dosages of IV iron and ESA; and hemoglobin levels were higher in Zerenex treated patients than in those receiving active control.
The investigators cited an analysis of the trial results that indicated that the projected reduction in the need for IV iron and ESA use would result in significant pharmaco-economic benefits. In addition, the investigators wrote, "one would postulate that decreased IV iron and ESA usage could result in decreased nursing time to administer IV medications which could be redirected to other aspects of patient care and decreased risk of infections due to fewer IV injections." In the PERFECTED study, fewer serious adverse events (SAEs) due to infection were seen in the subjects randomized to Zerenex compared to active control.
The authors noted that, if approved, Zerenex would be the only phosphate binder that also increases iron stores and decreases IV iron and ESA use.
Study Design and Results
Subjects in the PERFECTED study (n=441) first entered a 2-week washout period and were then randomized in a 2:1 ratio to receive either Zerenex or an active control of Renvela® (sevelamer carbonate) and/or Phoslo® (calcium acetate) for a 52-week Active Control Period. This was then followed by a 4-week Placebo Control Period in which Zerenex subjects were again randomized to either continue on Zerenex or switch to placebo. Zerenex was administered as 1 gram tablets each containing 210 mg of ferric iron. Active control study drugs were administered as calcium acetate 667 mg capsules, sevelamer carbonate 800 mg tablets alone or in combination.
The primary end-point of this trial was the mean change in serum phosphorus from baseline (Week 52) to the end of the 4-week Placebo Control Period. A prospectively designed sequential gatekeeping strategy controlled study-wise type 1 error for serum ferritin, TSAT, IV iron and ESA usage as pre-specified secondary endpoints in the 52-week Active Control Period.
The primary end-point demonstrated mean serum phosphorus was lower in the ferric citrate group versus the placebo group with a mean treatment difference of -2.2 ± 0.2 mg/dL (P <0.0001) at the end of the 4-week Placebo Control Period. The results demonstrated increased serum ferritin (P<0.0001) and TSAT (P<0.0001) compared to active control; decreased IV iron usage (P<0.0001) and decreased ESA usage (P=0.04). Additionally, mean hemoglobin levels were higher in subjects treated with Zerenex compared to active control (P=0.018) over 52 weeks.
Zerenex appeared safe and well tolerated in this study. Serious and non-serious adverse events (AE's) were similar between the two groups (Zerenex 90.3%, active control 89.3%), with the most common adverse events gastrointestinal-related, including diarrhea, nausea, vomiting and constipation. Adverse events were generally characterized as mild to moderate in nature. Serious adverse events were reported in 39.1% of subjects receiving Zerenex and 49.0% of active control subjects. Of interest, fewer SAE's were reported in the Zerenex group compared to the active control group in the categories of infection, cardiovascular and gastrointestinal (MEDRA terms). In addition, there were no clinically or statistically-significant differences in liver enzymes or aluminum levels between the treatment arms.
Zerenex™ (ferric citrate), is an oral, ferric iron-based phosphate binder. Keryx has completed a U.S.-based phase 3 clinical program for Zerenex for the treatment of hyperphosphatemia (elevated phosphate levels) in ESRD patients on dialysis, conducted pursuant to a Special Protocol Assessment (SPA) agreement with the FDA. To date, over 1,500 CKD patients have been exposed to Zerenex through completed phase 2 and 3 clinical trials. The Company's New Drug Application (NDA) is currently under review by the FDA with an assigned Prescription Drug User Fee Act (PDUFA) goal date of September 7, 2014. Keryx has filed a Marketing Authorization Application (MAA) with the European Medicines Agency (EMA), seeking the approval of Zerenex as a treatment of hyperphosphatemia in patients with all stages of CKD and that application is currently under review.
About Keryx Biopharmaceuticals, Inc.
Keryx Biopharmaceuticals, headquartered in New York, is focused on bringing innovative therapies to market for patients suffering from renal disease. In the United States, ferric citrate is currently under review by the Food and Drug Administration (FDA) for the treatment of hyperphosphatemia in dialysis-dependent chronic kidney disease (CKD) patients, where, pending approval, it will be marketed as Zerenex™ by Keryx. In January 2014, ferric citrate was approved for the treatment of patients with all stages of CKD in Japan, where it is being marketed as Riona® by Keryx's Japanese partner, Japan Tobacco Inc. and Torii Pharmaceutical Co. Ltd.
Some of the statements included in this press release, particularly those regarding the FDA's review, potential approval and subsequent commercialization of Zerenex, 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: the risk that the FDA, and/or EMA could ultimately deny approval of the U.S. NDA, and/or MAA, respectively; that the FDA and EMA may not concur with our interpretation of our Phase 3 study results, supportive data, or the conduct of the studies; whether Riona® will be successfully launched and marketed by our Japanese partner, Japan Tobacco, Inc. and Torii Pharmaceutical Co., Ltd.; whether, Zerenex, if approved by the FDA and/or EMA, will be successfully launched and marketed; and other risk factors identified from time to time in our reports filed with the Securities and Exchange Commission. Any forward-looking statements set forth in this press release speak only as of the date of this press release. We do not undertake 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.