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

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(r) (sevelamer carbonate) and/or Phoslo(r) (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.