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FDA Approves Iron-Replacement Drug Triferic
The FDA has approved Triferic for commercial sale as an iron-replacement product to maintain hemoglobin in adult patients with hemodialysis-dependent chronic kidney disease.
Triferic (soluble ferric pyrophosphate) is an iron compound that is delivered to hemodialysis patients via dialysate, replacing the ongoing iron losses that occur during their dialysis treatment. Triferic is introduced into bicarbonate concentrate at the dialysis clinic and is subsequently mixed into dialysate. Once in dialysate, Triferic crosses the dialyzer membrane and enters the blood, where it immediately binds to transferrin and is transported to erythroid precursor cells to be incorporated into hemoglobin.
Delivered with each hemodialysis treatment (three or four times per week), Triferic is able to compensate for the estimated 5 to 7 mg of iron loss from ongoing gastrointestinal and hemodialysis-related blood losses that occur in hemodialysis-dependent patients.
Primary efficacy evidence for Triferic was obtained from two identical, placebo-controlled, phase III studies in a total of 585 dialysis patients. The subjects initially entered a 1- to 4-week run-in period (stage 1) in which no study drug (Triferic) was administered. During the course of stage 1, patients meeting criteria for enrollment were entered into the randomized treatment period (stage 2) and were dialyzed with dialysate containing either Triferic (2 mcM [110 mcg of iron/L of dialysate]; n = 290) or placebo (n = 295). Patients completed the study at 48 weeks. Stage 2 was the evaluation period for the trial’s efficacy endpoint, the mean change in hemoglobin concentration from baseline to end-of-treatment (EoT).
The results of each of the phase III efficacy studies demonstrated a statistically significant and clinically meaningful treatment difference of 0.36 g/dL in favor of Triferic in the mean change in hemoglobin from baseline to EoT (P = 0.011 for both studies). Results from pooled analyses also demonstrated a treatment difference from placebo of 0.36 g/dL (P < 0.001 for combined results). Both the individual and combined results showed that the hemoglobin concentration was maintained with Triferic, but there was a significant decrease with placebo.
The safety profile of Triferic was similar to that of placebo in these pivotal trials. Triferic was not associated with the risk of serious adverse events associated with current intravenous iron therapies, such as exacerbation of oxidative stress, inflammation, cardiovascular disease, and the production of circulating NTBI. In addition, Triferic is free of carbohydrate, minimizing the risks of anaphylactoid reactions.
Sources: Rockwell Medical; January 26, 2015; FDA Briefing Document; October 6, 2014.