During Kidney Week 2016, Robert L. Chioini, founder, chairman, and chief executive officer of Rockwell Medical presented an overview of Triferic®, the only FDA-approved drug indicated to replace iron at every dialysis treatment and maintain hemoglobin in adult patients with chronic kidney disease (CKD) on a regimen of regular hemodialysis. Triferic (ferric pyrophosphate citrate) was highlighted during an Exhibitor Spotlight at the American Society of Nephrology Kidney Week in Chicago, Illinois.
Blood loss occurs at every dialysis session, as frequently as three times a week, 156 treatments every year. This loss can be attributed to needle sticks, blood trapped in blood lines, blood trapped in dialyzer, and draws for laboratory testing. Constant blood loss is associated with anemia in patients on hemodialysis, resulting in feelings of weakness and tiredness, making it optimal to replace iron at every hemodialysis treatment.
Triferic, a water-soluble iron complex, crosses the dialyzer membrane and replaces the 5- to 7-mg iron loss at every dialysis session, via the dialysate used in the treatment. Once in the blood, Triferic immediately and completely binds to transferrin and is transported to bone marrow for hemoglobin incorporation. The drug is tightly bound to pyrophosphate and therefore does not result in any free iron to promote oxidative stress or inflammation or increase in ferritin.
The mechanism of action of Triferic is similar to that of dietary iron in maintaining hemoglobin. There is no carbohydrate moiety, no increase in hepcidin, and no entrapment of iron in the liver. Further, there are no increases in iron stores, no anaphylaxis (>100,000 doses), and no free iron or oxidative stress. Delivery of Triferic is accomplished via liquid bicarbonate; it works in any central feed system with no changes required for cleaning the system.
In contrast, IV iron products are carbohydrate-encased, increase inflammation and metabolize and become trapped in the liver, resulting in increased ferritin and increased risk of infections and cardiovascular disease. Following the FDA approval of IV iron in the 1990s, the average ferritin for patients in the United States on hemodialysis has increased from ~200 µg/l to 800 µg/L, and >20% have ferritin above 1200 µg/L. In addition, there has been a significant rise in infections directly attributed to use of IV iron and high ferritin levels.
Among patients on hemodialysis, functional iron deficiency (FID) occurs when iron is present in the body but cannot be mobilized to transferrin and the bone marrow due to high levels of inflammation. IV iron metabolizes in the liver; inflammation activates hepcidin, preventing IV iron from leaving the liver, resulting in FID and high ferritin and infection. Approximately 1 gram of iron is lost in dialysis patients annually, yet, on average, patients receive 3.6 grams of IV iron annually.
Triferic administered during 20 dialysis treatments, over a 7-week period, is equivalent to just one typical dose of IV iron. The agent has a proven safety record based on the largest safety database ever submitted for registration of any parenteral iron product. The data include information on 1440 patients who received Triferic at every hemodialysis treatment for up to 18 months, representing 870 patient-years of exposure. In the more than 100,000 doses of Triferic administered, there has been no anaphylaxis, no increase in intradialytic hypotension, no increase in infections, no iron toxicity or overload, no increase in oxidative stress or inflammation. Further, administration of Triferic resulted in a more than 50% decrease in blood transfusions compared to placebo. The overall adverse event profile is similar to that of placebo. Triferic demonstrates a consistent and well-defined safety profile that makes the drug suitable for use as a long-term maintenance therapy.
The pharmacoeconomic benefits of Triferic include elimination of the cost of the needle/syringe needed for administration of IV iron, resulting in approximately a 20 cent cost reduction per treatment. In clinical study (PRIME), Triferic demonstrated a 35% reduction in erythropoietin-stimulating agent use versus placebo. There are also substantial reductions in nursing hours compared with IV iron administration and other anemia management tasks; estimates are that Triferic can save approximately 3 million nursing hours, freeing nurses delivering quality patient care. In addition, maintaining stable hemoglobin and iron levels may result in meeting Centers for Medicare & Medicaid Services Quality Improvement Project anemia values, resulting in an additional $5 reimbursement per treatment ($780 per patient per year).
“We believe this drug is going to become the standard of care in dialysis for iron replacement, not only in the United States but globally as well. It is a matter of patient and provider education. Triferic is safer, more effective, and provides considerable cost saving benefits,” Mr. Chioini added.