BOSTON, Nov. 07, 2017 (GLOBE NEWSWIRE) — Keryx Biopharmaceuticals, Inc. (Nasdaq:KERX), a company focused on bringing innovative medicines to people with kidney disease, today announced that the U.S. Food and Drug Administration (FDA) has approved Auryxia for an additional indication. The approval is for the treatment of iron deficiency anemia in adults with chronic kidney disease (CKD), not on dialysis. Auryxia was originally approved in September 2014 for the control of serum phosphorus levels in people with chronic kidney disease who require dialysis.
With the new indication, millions of people living with chronic kidney disease have the potential to benefit from treatment with Auryxia. This medication is available today in pharmacies and covered broadly by Medicare Part D and commercial insurance providers in the United States.
“More than half of the approximate 30 million people in the United States living with chronic kidney disease are iron deficient, and yet, this is the only tablet that has been developed and approved specifically to address iron deficiency anemia in these patients, who are not on dialysis,” said Steven Fishbane, M.D., chief, division of kidney diseases and hypertension, department of medicine, Northwell Health in Great Neck, New York. “Starting today, physicians can prescribe an oral iron medicine to help people living with this condition, the majority of whom are not being optimally treated.”
“We are pleased with the broad indication permitted by the FDA, as a first-line treatment option for adults with iron deficiency anemia and chronic kidney disease, not on dialysis,” said John Neylan, M.D., senior vice president and chief medical officer of Keryx Biopharmaceuticals. “Physicians and their patients now have a new treatment option to help manage a serious complication of this complex disease.”
Auryxia’s supplemental new drug application (sNDA) approval was based on results from a 24-week placebo controlled Phase 3 clinical trial in 234 adults with stage 3-5 non-dialysis dependent chronic kidney disease. Patients enrolled in the trial had hemoglobin levels between 9.0 g/dL and 11.5 g/dL and were intolerant to or had an inadequate response to prior treatment with oral iron supplements. The starting dose in the study was three tablets per day taken with meals; the mean dose was five tablets per day. Importantly, during the study, patients were not allowed to receive any intravenous (IV) or oral iron, or erythropoiesis-stimulating agents (ESAs). In the study, treatment with Auryxia demonstrated significant increases in hemoglobin levels of >1 g/dL at any point during the 16-week efficacy period for the majority of patients (52.1 percent, n=61/117 compared to 19.1 percent, n=22/115 in the placebo group), a clinically meaningful result. In the trial, ferric citrate was generally well tolerated and adverse events were consistent with its known safety profile. The most commonly reported adverse events in the Phase 3 study were diarrhea (21%), constipation (19%), discolored feces (15%), nausea (11%), abdominal pain (6%) and hyperkalemia (7%). Results were published January 2017 in the online issue of the Journal of the American Society of Nephrology (JASN).
Patients with chronic kidney disease (CKD) suffer from multiple metabolic abnormalities, chief among them are disorders of mineral metabolism, including hyperphosphatemia, and disorders of iron metabolism, which can lead to both iron deficiency anemia and iron refractory anemia. The latter is in part, due to the inflammatory nature of CKD and dialysis and in part, due to erythropoietin deficiency, leading to chronic renal anemia. While erythropoiesis stimulating agents (ESA) can replace the deficiency of erythropoietin, optimal ESA response requires the concomitant administration of intravenous iron [see here]. Orally administered iron supplements are not effective in restoring iron stores in ESRD patients and are associated with gastrointestinal symptoms.
Ferric citrate [Auryxia®], initially developed as a phosphate binder, was found to also improve iron deficiency anemia in CKD patients, due to the absorption of iron from the GI tract. Previously marketed phosphate binders have included aluminum hydroxide, which was shown to result in aluminum deposition in bone and in brain in ESRD. The former can lead to osteomalacia, while the latter is associated with encephalopathy. For these reasons, the use of aluminum hydroxide as a phosphate binder has been abandoned. Calcium carbonate, although an effective phosphate binder, was shown to result in hypercalcemia, over-suppression of parathyroid hormone and adynamic bone disease as well as coronary artery and cardiac calcifications [see here]. These side effects led to the development of aluminum-free and calcium-free phosphate binders such as Sevelamer (Renagel®, Renvela®) and lanthanum carbonate (Fosrenol®]. Lanthanum carbonate does not result in any significant lanthanum absorption and has not been shown to have any untoward consequences [see here]. Sevelamer is a non-absorbable resin, so its action is limited to binding phosphate and bile acids in the gut.
The development of ferric citrate as a phosphate binder was a departure from the previous strategies of developing non-absorbable phosphate binding compounds. This new approach has paid off in that, iron deficiency, a common problem in pre-dialysis CKD patients, was shown to improve with ferric citrate, while it was primarily prescribed as a phosphate binder [Block 20015; Fishbane 2017]. The approval of the supplemental application for the use of ferric citrate [Auryxia®] to treat iron-deficiency anemia in pre-dialysis CKD patients, should now allow patients to obtain re-imbursement for this indication. Of course, ferric citrate will continue to be used for its primary indication as a phosphate binder in ESRD patients on dialysis. In this indication, the additional benefit of ferric citrate is the reduced need for intravenous iron and to also the reduction in the ESA dose [see here]and [here]. Considering the high costs of these treatments, reduced doses is likely to reduce the overall cost of anemia treatment, which is currently bundled under the CMS rules [see here].
Copyright © M. Loghman-Adham, MD
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How ‘Bundling’ Changed Dialysis Care. Renal & Urology News March 02, 2017 (see here)