Safety and Efficacy Of Ferumoxytol For The Episodic Treatment Of Iron Deficiency Anemia In Patients With a History Of Unsatisfactory Oral Iron Therapy: Results Of a Phase III Open-Label, Six Month Extension Study

Abstract

▪ BackgroundThe efficacy of intravenous iron replacement in treating iron deficiency anemia (IDA) has been studied in patients with various underlying conditions. In some conditions like abnormal uterine and gastrointestinal bleeding, there may be ongoing blood loss leading to a continuing need for treatment that may require episodic iron replacement. MethodsA 6 month Phase III, open-label extension study was designed to evaluate the safety and efficacy of ferumoxytol (FER) for the episodic treatment of IDA patients with a history of unsatisfactory oral iron therapy or in whom oral iron could not be used. The study enrolled patients from a double-blind, placebo (P)-controlled 5-week Phase III study, who had been randomized 3:1 to treatment with FER or P and completed that study. Enrolled patients were evaluated for IDA monthly throughout the 6-month Observation Period. Those with persistent or recurrent IDA (defined as Hgb <11.0 g/dL and TSAT <20%) at any evaluation visit, began a 5-week Treatment Period (TP), receiving a course of FER (2 x 510 mg) with response assessed at TP Week 5. ResultsThis extension study enrolled 78.5% of patients from the previous Phase III study (163/200 P, 471/608 FER), of whom 93% of the P- and 39% of the FER-treated patients met treatment criteria during the 6-month extension and received at least 1 course of FER. In the remaining (12 P, 285 FER) patients, mean monthly Hgb remained ≥12.1 g/dL without further treatment. Mean Hgb increased significantly (p<0.0001) from TP Baseline to TP Week 5 following Treatment Course 1 (2.6 g/dL; N=151) and repeat courses (Course 2: 1.5 g/dL, N=244 [38.5%]; Course 3: 1.1 g/dL, N=69 [10.9%]); mean Week 5 Hgb was comparable following Courses 1, 2 and 3. The few patients receiving Treatment Courses 4 (N=18) or 5 (N=4) limited further analyses. Overall, 61% of FER treated patients never required a 2nd course of treatment. Statistically significant (p<0.0001) increases in mean TSAT from TP Baseline to TP Week 5 followed Course 1 and subsequent courses.FER was also well-tolerated and no new safety signals were observed among patients who received repeat dosing. The incidence of treatment emergent adverse events (TEAEs) was 47.7%, 38.1% and 37.7% in patients who received Course 1, 2 and 3 of FER, respectively. The pattern of related TEAEs decreased in subsequent courses, and none were reported in patients who received more than 3 courses. The incidence of serious adverse events (SAEs) was comparable in patients who received Course 1, 2 and 3, and most were attributable to comorbidities and/or procedural complications; no related SAEs or deaths were reported. For all other TEAE categories, no clear pattern of incidence was observed between Treatment Courses. [Display omitted] ConclusionFER (2x 510 mg) delivered over multiple treatment courses was generally well tolerated in IDA patients with a history of unsatisfactory oral iron therapy or in whom oral iron could not be used with persistent or recurrent IDA; Week 5 post-treatment Hgb was comparable following Courses 1, 2 and 3. No trend of increasing incidence of TEAEs was identified with repeat dosing, and a consistent, positive and robust treatment effect was observed. Durability of the treatment effect following FER was demonstrated by the majority of patients not requiring further iron treatment following the initial course during this 6 month extension study. Disclosures:Vadhan-Raj:AMAG Pharmaceuticals, Inc: Research Funding. Off Label Use: Feraheme (ferumoxytol) injection. For treatment of iron deficiency anemia in non-CKD patients. Dahl:AMAG Pharmaceuticals, Inc: Employment. Lau:AMAG Pharmaceuticals, Inc: Employment. Bernard:AMAG Pharmaceuticals, Inc: Employment. Li:AMAG Pharmaceuticals, Inc: Employment. De:AMAG Pharmaceuticals, Inc: Employment. Allen:AMAG Pharmaceuticals, Inc: Consultancy. Strauss:AMAG Pharmaceuticals, Inc: Employment.FER Received in Extension Study (N=337) Treatment Course‡Course 1 (N=151)Course 2 (N=244)Course 3 (N=69)Efficacy Results (ITT Population)Mean Change in Hgbµ2.6 (1.6)*1.5 (1.3)*1.1 (1.3)*% Patients with Increase in Hgb ≥ 2.0 g/dL¥78.843.937.7Mean Change in TSAT (%)µ12.8 (10.2)*11.7 (12.5)*7.5 (9.1)*Safety Results (Safety Population)All AEs47.7%38.1%37.7%Related AEs12.6%5.3%2.9%SAEs4.6%4.9%4.3%Related SAEs000AEs of Special Interest- protocol-defined€00.4%0Cardiovascular AE Composite EndpointΩ1.3%0.8%1.4%AEs Resulting in Study Discontinuation2.6%04.3%Death000* p-value <0.0001 based on paired t-test‡ Course numbering based on treatment received in placebo-controlled studyµ from Baseline to Week 5¥ at any time from Baseline to Week 5€ includes protocol defined signs and symptoms of hypotension and hypersensitivityΩ includes myocardial infarction, heart failure, moderate to severe hypertension and hospitalization due to any cardiovascular cause