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Study 1: Injectafer vs oral iron and vs IV iron Standard of Care

Study 1: Injectafer vs oral iron and vs IV iron standard of care (SoC)1

Study 1:
Injectafer vs oral iron
and vs IV iron standard of
care (SoC)1

A randomized, open-label, multicenter study evaluating the efficacy and safety of Injectafer in adult patients with IDA of any etiology.

Injectafer clinical trial study Injectafer clinical trial study

Injectafer trials included patients with iron intolerance, drug allergy, and hypotension1,2

Injectafer trials included patients with iron intolerance, drug allergy, and hypotension1,2

*Participants who responded adequately to oral iron during run-in (Hb increase ≥1 g/dL) were not randomized.

Subjects inappropriate for oral iron were defined as either those who were intolerant of oral iron during the run-in phase or those in whom the baseline Hb measurement was sufficiently low as to require rapid repletion of iron stores to minimize the risk of eventual blood transfusion. These patients were not included in the indication for Injectafer.

The efficacy analyses were performed on the modified intent-to-treat (mITT) population, which included all patients who received at least 1 dose of randomized treatment and had at least 1 post-baseline Hb assessment.

§The safety population consisted of all subjects who received a dose of randomized treatment. All safety analyses were performed with the Safety Population.

STUDY 1, COHORT 1: INJECTAFER VS ORAL IRON

Injectafer provided significantly greater increase in Hb

Injectafer provided
significantly greater
increase in Hb

  • Cohort 1 consisted of patients with iron deficiency anemia who did not have a satisfactory response to oral iron in a 14-day run-in period1

Greater absolute increase in Hb1

Mean change from baseline to day 35 on Hb levels with Injectafer. Injectafer 1.6. Oral iron 0.8. Mean change from baseline to day 35 on Hb levels with Injectafer. Injectafer 1.6. Oral iron 0.8.

Injectafer helped patients achieve Hb target of >12 g/dL1

Study of Injectafer on Hb from  baseline to day 35 Study of Injectafer on Hb from  baseline to day 35

Improvements in ferritin and TSAT1,3

Ferritin: Mean change from baseline to day 35 or time of intervention. Injectafer 264.21 vs -3.83 for oral iron. TSAT: Mean change from baseline to day 35 or time of intervention. Injectafer 12.99% vs -5.70 for oral iron. Ferritin: Mean change from baseline to day 35 or time of intervention. Injectafer 264.21 vs -3.83 for oral iron. TSAT: Mean change from baseline to day 35 or time of intervention. Injectafer 12.99% vs -5.70 for oral iron.

The diminished iron stores, as seen by the ferritin and TSAT levels, in the oral iron arm of this study suggest that iron losses outpaced iron supplementation1

Patients meeting endpoint with Injectafer 7 (2.9%), Oral iron 4 (1.6%) Patients meeting endpoint with Injectafer 7 (2.9%), Oral iron 4 (1.6%)

  • The most commonly observed components of the composite safety endpoint were protocol-defined hypertension (4 participants in Cohort 1, Injectafer arm; 7 participants in Cohort 2, Injectafer arm; and 6 participants in Cohort 2, SoC IV iron arm) and death due to any cause (2 participants in Cohort 1, oral iron arm)1

In Injectafer clinical trials, serious anaphylactic/anaphylactoid reactions were reported in 0.1% (2/1775) of subjects receiving Injectafer3

In Injectafer clinical trials, serious anaphylactic/anaphylactoid reactions were reported in 0.1% (2/1775) of subjects receiving Injectafer3

|| Standard deviation.

Post-hoc comparison.

STUDY 1, COHORT 2: INJECTAFER VS IV IRON SoC

Injectafer provided significantly greater increase in Hb

  • Cohort 2 consisted of patients who tolerated oral iron poorly or were inappropriate for treatment with oral iron
  • 90% of patients randomized to IV iron SoC received iron sucrose1

Greater absolute increase in Hb1

Mean change in absolute value from baseline to day 35 or time of intervention. Injectafer 2.9 vs IV iron SoC 2.2 Mean change in absolute value from baseline to day 35 or time of intervention. Injectafer 2.9 vs IV iron SoC 2.2

Injectafer helped patients achieve Hb target of >12 g/dL1

Percentage of patients reaching Hb > 12 g/dL between baseline and day 35 or time of intervention. Injectafer 51% vs IV iron SoC 25% Percentage of patients reaching Hb > 12 g/dL between baseline and day 35 or time of intervention. Injectafer 51% vs IV iron SoC 25%

Injectafer provided greater improvements in ferritin and TSAT

Improvements in ferritin and TSAT1

Ferritin: Mean change from baseline to day 35 or time of intervention. Injectafer 218.15 vs 74.65 for IV iron SoC. TSAT: Mean change from baseline to day 35 or time of intervention. Injectafer 20.18% vs 8.77% for IV iron SoC. Ferritin: Mean change from baseline to day 35 or time of intervention. Injectafer 218.15 vs 74.65 for IV iron SoC. TSAT: Mean change from baseline to day 35 or time of intervention. Injectafer 20.18% vs 8.77% for IV iron SoC.

No significant difference was shown at the primary composite safety endpoint1

Injectafer patients meeting endpoint: 7 (2.9%) Oral iron patients meeting endpoint: 4 (1.6%) Injectafer patients meeting endpoint: 7 (2.9%) Oral iron patients meeting endpoint: 4 (1.6%)

  • The most commonly observed components of the composite safety endpoint were protocol-defined hypertension (4 participants in Cohort 1, Injectafer arm; 7 participants in Cohort 2, Injectafer arm; and 6 participants in Cohort 2, SoC IV iron arm) and death due to any cause (2 participants in Cohort 1, oral iron arm)1

#Standard deviation.

**Post-hoc comparison.

EFFICACY & SAFETY: Study 2 (REPAIR-IDA): Injectafer vs IV iron sucrose in NDD-CKD

Important Safety Information

INDICATIONS

Injectafer® (ferric carboxymaltose injection) is indicated for the treatment of iron deficiency anemia (IDA) in adult patients who have intolerance to oral iron or have had unsatisfactory response to oral iron, or who have non-dialysis dependent chronic kidney disease.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

Injectafer is contraindicated in patients with hypersensitivity to Injectafer or any of its inactive components.

WARNINGS AND PRECAUTIONS

Symptomatic hypophosphatemia requiring clinical intervention has been reported in patients at risk of low serum phosphate in the postmarketing setting. These cases have occurred mostly after repeated exposure to Injectafer in patients with no reported history of renal impairment. Possible risk factors for hypophosphatemia include a history of gastrointestinal disorders associated with malabsorption of fat-soluble vitamins or phosphate, concurrent or prior use of medications that affect proximal renal tubular function, hyperparathyroidism, vitamin D deficiency and malnutrition. In most cases, hypophosphatemia resolved within three months.

Monitor serum phosphate levels in patients at risk for low serum phosphate who require a repeat course of treatment.

Serious hypersensitivity reactions, including anaphylactic-type reactions, some of which have been life-threatening and fatal, have been reported in patients receiving Injectafer. Patients may present with shock, clinically significant hypotension, loss of consciousness, and/or collapse. Monitor patients for signs and symptoms of hypersensitivity during and after Injectafer administration for at least 30 minutes and until clinically stable following completion of the infusion. Only administer Injectafer when personnel and therapies are immediately available for the treatment of serious hypersensitivity reactions. In clinical trials, serious anaphylactic/anaphylactoid reactions were reported in 0.1% (2/1775) of subjects receiving Injectafer. Other serious or severe adverse reactions potentially associated with hypersensitivity which included, but were not limited to, pruritus, rash, urticaria, wheezing, or hypotension were reported in 1.5% (26/1775) of these subjects.

In clinical studies, hypertension was reported in 3.8% (67/1775) of subjects. Transient elevations in systolic blood pressure, sometimes occurring with facial flushing, dizziness, or nausea were observed in 6% (106/1775) of subjects. These elevations generally occurred immediately after dosing and resolved within 30 minutes. Monitor patients for signs and symptoms of hypertension following each Injectafer administration.

In the 24 hours following administration of Injectafer, laboratory assays may overestimate serum iron and transferrin bound iron by also measuring the iron in Injectafer.

ADVERSE REACTIONS

In two randomized clinical studies, a total of 1775 patients were exposed to Injectafer, 15 mg/kg of body weight, up to a single maximum dose of 750 mg of iron on two occasions, separated by at least 7 days, up to a cumulative dose of 1500 mg of iron. Adverse reactions reported by ≥2% of Injectafer-treated patients were nausea (7.2%); hypertension (3.8%); flushing/hot flush (3.6%); blood phosphorus decrease (2.1%); and dizziness (2.0%).

The following adverse reactions have been identified during post approval use of Injectafer. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

The following adverse reactions have been reported from the post-marketing spontaneous reports with Injectafer: cardiac disorders: tachycardia; general disorders and administration site conditions: chest discomfort, chills, pyrexia; metabolism and nutrition disorders: hypophosphatemia; musculoskeletal and connective tissue disorders: arthralgia, back pain, hypophosphatemic osteomalacia (rarely reported event); nervous system disorders: syncope; respiratory, thoracic and mediastinal disorders: dyspnea; skin and subcutaneous tissue disorders: angioedema, erythema, pruritus, urticaria.

You are encouraged to report Adverse Drug Events to American Regent, Inc. at 1-800-734-9236 or to the FDA by visiting www.fda.gov/medwatch or calling 1-800-FDA-1088.

Please see Full Prescribing Information.

Reference - Efficacy and Saftey