Zerenex(TM) (Ferric Citrate) Long-Term Phase 3 Study Results Published in the Journal of the American Society of Nephrology - Seite 3

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.

About Zerenex(TM)

Zerenex(TM) (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.