dm+d

Unassigned

New Medicines

Fexeric (EU), Auryxia (US)Hyperphosphataemia in dialysis and pre-dialysis renal failure

Information

Fexeric (EU), Auryxia (US)
New molecular entity
Keryx
Keryx

Development and Regulatory status

Licensed but not launched
Licensed but not launched
Launched
01. May 11: EMA have indicated PIII US trial programme will be sufficient for EU application [1].
02. Aug 13: Filed in the US for the treatment of elevated serum phosphorus levels, or hyperphosphataemia, in patients with CKD on dialysis. An EU filing is also planned [7].
03. Mar 14: Filed in the EU as a treatment for hyperphosphataemia in patients with chronic kidney disease (both dialysis- and non-dialysis dependent) [8].
04. Sept 14: Approved by US FDA for the control of serum phosphorus levels in patients with chronic kidney disease (CKD) on dialysis. [10]
05. Sept 14: US regulators warn about danger of iron overload with ferric citrate and that doctors must monitor iron parameters. Pharma company argue that this could reduce the use of IV iron therapy though. [11]
06. Jul 15: EU positive opinion for control of hyperphosphataemia in adults with CKD [12].
07. Sep 15: European Commission approves Fexeric® for control of hyperphosphatemia in adults with CKD, including both dialysis and pre-dialysis patients [13].
08. Sep 15: Keryx is working with potential partners regarding commercialisation in the EU, and expect to finalise their commercial strategy by end 2015 [13].
09. Auryxia was launched in the US in Dec 14 [13].
10. Mar 16: Based on the study of patients who had not adequately responded to or were unable to tolerate current oral iron therapies, Keryx said it would apply in Q3 2016 for an expanded approval with U.S. regulators for ferric citrate in moderate to advanced chronic kidney patients not dependent on dialysis [14].

Category

An orally available phosphate binder
Prevalence of CKD 4/5 is 1% or less in England (520,000 people). Nearly 26,000 are receiving dialysis [5]. Almost all pts with CKD 5 have hyperphosphataemia [6].
Hyperphosphataemia in dialysis and pre-dialysis renal failure
Oral

Trial or other data

01. May 11: Results of PIII study in 146 dialysis patients presented. The study met the primary endpoint (to determine whether there was a dose response in the change in serum phosphorus from Baseline to Day 28) with analysis indicating a highly statistically significant dose response (p
02. Sep 11: Completed enrolment of long-term study component of Phase III study for the treatment of elevated serum phosphorus levels (hyperphosphataemia) in patients with end-stage renal disease (ESRD) on dialysis. The study consists of a two-week washout period followed by a 52-week safety assessment in which patients are randomised (2:1) to receive either Zerenex or an active control, followed by a four-week efficacy assessment [3].
03. Jan 13: Results from a PIII long-term study in 441 ESRD patients on hemodialysis or peritoneal dialysis reported, randomised 2:1 to receive either Zerenex or an active control (sevelamer carbonate &/or calcium acetate) for 52 wks. Subjects randomised to treatment with Zerenex were the randomised in a 1:1 ratio to either continue treatment with Zerenex or switch to placebo for a 4-week treatment period. Subjects were titrated during the study to achieve serum phosphorus levels that ranged between 3.5 to 5.5 mg/dL. Zerenex met the primary efficacy endpoint (mean change in serum phosphorus from baseline (Week 52) to end of the four-week Efficacy Assessment Period (Week 56) in the ITT group (n=183) 1.9 vs. -0.3 (Least Squares (LS) Mean Difference from Placebo -2.3; p
04. Jul 14: PIII PERFECTED study (PhosphatE binding and iRon delivery with FErric CiTrate in EsrD) published in the Journal of the American Society of Nephrology. 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 [9].
05. Mar 16: Keryx announces ferric citrate met the goals of a late stage clinical trial to treat iron deficiency anemia in chronic kidney disease patients not yet requiring dialysis , potentially paving the way for an expanded approval of the treatment. In the 16-week study of 234 patients with moderate to severe kidney disease, 52% of those who received ferric citrate saw their hemoglobin levels rise by at least 1g/dl of blood during the trial. That compared with 19% in the placebo group who experienced a 1g/dl increase. The initial results for the oral, iron-based drug were both statistically significant and clinically meaningful, the company said [14].

Evidence based evaluations