AMAG Pharmaceuticals, Inc., a specialty pharmaceutical company, announced positive preliminary data from the IDA-303 study. IDA-303 is a single arm, open-label extension study that evaluated the safety and efficacy of repeat dosing with ferumoxytol in patients with persistent or recurring iron deficiency anaemia (IDA) regardless of the underlying cause and a history of unsatisfactory oral iron therapy or in whom oral iron could not be used. Patients were eligible to enroll in the IDA-303 extension study after they completed IDA-301, which was a double-blind, placebo-controlled trial that randomized patients to receive either a one gram intravenous course of ferumoxytol or placebo, the results of which were previously reported by the company and presented at the American Society of Hematology annual meeting in December 2012.
A total of 634 patients were enrolled and qualified for ongoing observation/treatment in IDA-303. Of the 634 patients enrolled in IDA-303, 471 had previously received one treatment course with ferumoxytol in the IDA-301 study, and the remainder had received placebo. Patients were eligible for ferumoxytol treatment in IDA-303 if their haemoglobin levels fell below 11 g/dL and their transferrin saturation (TSAT) levels were less than 20%. During the course of the IDA-303 study, 337 patients were treated with ferumoxytol; 151 of these patients had received placebo in IDA-301 and therefore received their first course of ferumoxytol in the IDA-303 study. A total of 244 patients received a second course of ferumoxytol, of whom 186 patients had received their first course in IDA-301. The remainder of patients enrolled in IDA-303 did not receive treatment, suggesting the durability of response to the first course of ferumoxytol administered in the IDA-301 study.
The primary efficacy endpoint of the extension study was the mean change in haemoglobin from baseline to week five following the first course of ferumoxytol. The 151 patients who received their first course of therapy in IDA-303 achieved a statistically significant mean increase in haemoglobin from baseline to week five of 2.6 g/dL. This change was consistent with the 2.7 g/dL increase in haemoglobin reported for ferumoxytol-treated patients in both the IDA-301 and IDA-302 studies.
The first secondary endpoint was the mean change in haemoglobin from baseline to week five for each subsequent course of ferumoxytol after treatment course one. The group of patients receiving a second (n=244) and third (n=69) course of treatment with ferumoxytol in IDA-303 included patients who had received ferumoxytol in IDA-301 and patients who had received their first course of ferumoxytol in IDA-303. With repeat dosing, ferumoxytol also demonstrated a statistically significant increase in mean hemoglobin from baseline to week five, with a mean haemoglobin increase of 1.5 g/dL following treatment course two and a 1.1 g/dL increase following treatment course three. The mean haemoglobin level achieved by patients at week five following each of the first three treatment courses with ferumoxytol were all comparable, with the mean haemoglobin levels in course one of 11.7 g/dL, in course two of 11.9 g/dL, and in course three of 11.4 g/dL, suggesting the consistent effect of ferumoxytol treatment with repeat dosing. Only a small number of patients (n=18) received four or more courses of ferumoxytol over the 6 month duration of the study, limiting formal analyses of these data.
No new safety signals were observed with repeat dosing of ferumoxytol and the types of reported adverse events (AEs) were consistent with those seen in both the previously reported IDA and CKD phase III studies, and those contained in the approved U.S. package insert for Feraheme; no hypersensitivity reactions or hypotension were reported in the IDA-303 study. Approximately 48 peracent of patients who received ferumoxytol treatment course one in this study experienced an adverse event, consistent with the AE rate reported in the IDA-301 study; in each of treatment courses two and three, approximately 38 per cent of patients experienced an AE. Approximately 5 per cent of ferumoxytol-treated patients in this study experienced a serious adverse event in each of the three treatment courses, none of which were deemed related to treatment by study investigators.
Protocol-defined adverse events of special interest (AESI) for the IDA studies were defined to include mild to severe hypotension or hypersensitivity reactions or associated symptoms. There was one AESI, shortness of breath (or dyspnea), which was reported as not related to treatment in one patient who received a second course of ferumoxytol. Cardiovascular AEs, deemed not related to treatment, were reported in approximately 1 percent of ferumoxytol-treated patients in each of the three treatment courses. No deaths were reported in this study.
“We are pleased to see the consistency of both the safety and efficacy data observed across the full IDA phase III programme in studies IDA-301, IDA-302 and now IDA-303,” said William Heiden, president and chief executive officer of AMAG. “The final data from this study will be included in the registration package for ferumoxytol in Europe in pursuit of the broader IDA indication, which we expect will be filed this year.”
In December 2012, AMAG submitted a supplemental new drug application (sNDA) to the United States Food and Drug Administration (FDA) for Feraheme (ferumoxytol) Injection for Intravenous (IV) requesting FDA approval to expand the indication for ferumoxytol beyond the current approved indication for the treatment of IDA in adult patients with chronic kidney disease to all adult patients with IDA who have failed or could not tolerate oral iron treatment. This sNDA is currently under review with the FDA. Under the Prescription Drug User Fee Act (PDUFA) guidelines, the FDA has set October 21, 2013 as a target date for completion of their review.
More than 4 million Americans have IDA; 1.6 million of whom are estimated to have CKD, while the other 2.4 million suffer from anemia due to other causes.1 For these patients with anemia due to other causes, the underlying diseases or issues causing IDA include abnormal uterine bleeding, gastrointestinal disorders, inflammatory diseases and chemotherapy-induced anemia. Many IDA patients fail treatment with oral iron due to intolerability or side effects.