Clinical Trials

Date: 2017-05-02

Type of information: Results

phase: 3

Announcement: results

Company: Amag Pharmaceuticals (USA - MA)

Product: Feraheme® (ferumoxytol)

Action mechanism: Ferumoxytol is a colloidal iron-carbohydrate complex. Upon release from the complex, the iron either enters the intracellular storage iron pool (e.g., ferritin) or is transferred to plasma transferrin for transport to erythroid precursor cells for incorporation into haemoglobin. The benefits with Rienso® are its ability to increase haemoglobin levels.

Disease: iron deficiency anemia (IDA)

Therapeutic area: Metabolic diseases

Country: USA

Trial details: The non-inferiority, randomized, double-blind, multicenter clinical trial is evaluating the incidence of moderate-to-severe hypersensitivity reactions (including anaphylaxis), and moderate-to-severe hypotension with Feraheme® compared to Injectafer® in adults with IDA. Approximately 2,000 patients diagnosed with IDA regardless of underlying etiology were randomized in a 1:1 ratio into one of two treatment groups – 1.02 grams of Feraheme intravenous (IV) infusion (n=997) or 1.5 grams of Injectafer IV infusion (n=1,000). This is the final trial that Amag Pharmaceuticals plans to conduct in preparation for filing the sNDA to broaden the use of Feraheme® beyond the current chronic kidney disease (CKD) indication to include all adult IDA patients who have failed or cannot tolerate oral iron treatment or in whom oral iron was contraindicated.

Latest news:

• • On May 2, 2017, Amag Pharmaceuticals announced top-line results from a Phase 3 randomized, double-blind, non-inferiority clinical trial evaluating Feraheme® (ferumoxytol) compared to Injectafer® (ferric carboxymaltose injection) in approximately 2,000 adults with iron deficiency anemia (IDA). The study results demonstrated non-inferiority to Injectafer based on the primary composite endpoint of incidence of moderate-to-severe hypersensitivity reactions (including anaphylaxis) and moderate-to-severe hypotension. Additionally, the trial met secondary safety and efficacy endpoints, including the demonstration of superiority to Injectafer regarding mean improvement in hemoglobin per gram of iron administered from baseline to week 5.
• Feraheme met the study’s primary endpoint demonstrating non-inferiority to Injectafer (based on an NI margin of 2.64%) with respect to the percentage of patients who experienced moderate-to-severe hypersensitivity reactions (including anaphylaxis) and/or moderate-to-severe hypotension (Feraheme: 0.6%; Injectafer: 0.7%; treatment difference: -0.1%; 95% confidence interval: -0.80% to +0.61%; NI p=<0.0001).
• Feraheme also demonstrated non-inferiority to Injectafer for a secondary composite safety endpoint assessing incidence of moderate-to-severe hypersensitivity reactions (including anaphylaxis), serious cardiovascular events, and/or death (based on an NI margin of 3.6%) (Feraheme: 1.3%; Injectafer: 2.0%; treatment difference: -0.7%; 95% confidence interval: -1.81% to +0.42%; NI p=<0.0001). With regards to secondary composite efficacy endpoints, the study demonstrated superiority of Feraheme to Injectafer in mean increase from baseline to week 5 in hemoglobin per gram of iron administered (Feraheme: 1.36 g/dL per gram of iron; Injectafer: 1.09 g/dL per gram of iron; treatment difference 0.27 g/dL per gram of iron; 95% confidence interval +0.17 g/dL per gram of iron to +0.36 g/dL per gram of iron; superiority p-value= <.0001). Feraheme also successfully demonstrated non-inferiority to Injectafer (based on an NI margin of 0.5 g/dL) comparing mean improvement in hemoglobin from baseline to week 5 (Feraheme: 1.38 g/dL; Injectafer: 1.62 g/dL; treatment difference: -0.24 g/dL; 95% confidence interval: -0.35 g/dL to -0.12 g/dL; NI p=<0.0001).
• The study also showed a markedly greater incidence of hypophosphatemia (an exploratory endpoint defined by blood phosphorous of <0.6 mmol/L at week 2) in the patients dosed with Injectafer versus those dosed with Feraheme (Feraheme: 0.4% of patients; Injectafer: 38.6% of patients; treatment difference: -38.2%; 95% confidence interval: -41.31% to ?35.06%; superiority p-value p<.0001). Amag expects to file a supplemental new drug application (sNDA) with the FDA by mid-2017 to potentially broaden the use of Feraheme beyond the current chronic kidney disease indication to include all adult iron deficiency anemia patients who have failed or cannot tolerate oral iron treatment, with an anticipated FDA decision in the first half of 2018.   • On October 12, 2016, Amag Pharmaceuticals announced that enrollment of patients in the Feraheme Phase 3 label expansion trial for the treatment of iron deficiency anemia has surpassed approximately two-thirds of the total target enrollment of 2,000 patients, resulting in the acceleration of the estimated supplemental new drug application (sNDA) filing date to mid-2017. This is the final trial that the company plans to conduct in preparation for filing the sNDA to broaden the use of Feraheme beyond the current chronic kidney disease indication to include all adult iron deficiency anemia patients who have failed or cannot tolerate oral iron treatment or in whom oral iron was contraindicated. Patient enrollment in the clinical trial has surpassed two-thirds of the total target enrollment mark ahead of schedule.
• • On October 28, 2015, Ama Pharmaceuticals announced that it has commenced start-up activities for its head-to-head Phase 3 clinical trial evaluating the safety of Feraheme® (ferumoxytol) compared to Injectafer® (ferric carboxymaltose injection) in adults with iron deficiency anemia (IDA). The planned safety trial follows the Complete Response Letter (CRL) AMAG received from the FDA in January 2014 regarding its supplemental new drug application (sNDA) to broaden the use of Feraheme beyond the current chronic kidney disease (CKD) indication to include all adult IDA patients who have failed or cannot tolerate oral iron treatment.
• The randomized, double-blind, multicenter non-inferiority trial will evaluate the incidence of moderate to severe hypersensitivity reactions (including anaphylaxis), and moderate to severe hypotension with Feraheme compared to ferric carboxymaltose injection in adults with IDA. Two thousand patients will be randomized in a 1:1 ratio into one of two treatment groups – 1.02 grams of Feraheme intravenous (IV) infusion or 1.5 grams of ferric carboxymaltose injection. While the trial's primary endpoint is safety, the study will also assess efficacy. AMAG expects to begin enrolling patients in the trial in the first quarter of 2016, with a potential sNDA approval and launch in 2018.

Is general: Yes