Feraheme ferumoxytol

1
Feraheme? / ferumoxytol

• Manufacturer AMAG Pharmaceuticals
• FDA Approval Date June 30, 2009

2
Feraheme? / ferumoxytol Clinical Application

• Indications
• Treatment of iron-deficiency anemia in chronic
  kidney disease (including dialysis dependent and
  non-dialysis dependent patients)
• Place in therapy
• An alternative intravenous iron replacement
  therapy with a more convenient dosing schedule

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Feraheme? / ferumoxytol Clinical Application

• Contraindications
• Evidence of iron overload
• Known hypersensitivity to Feraheme or any of its
  components
• Anemia not caused by iron deficiency
• Warnings and Precautions
• Hypersensitivity reactions observe for
  signs/symptoms of hypersensitivity for at least
  30 minutes following administration
• Hypotension monitor for signs/symptoms of
  hypotension following administration
• Iron overload regularly monitor hematologic
  response during therapy
• MRI studies may affect the diagnostic ability
  of magnetic resonance imaging for up to 3 months

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Feraheme? / ferumoxytol Drug Facts

• Pharmacology
• Ferumoxytol consists of a superparamagnetic iron
  oxide coated with a carbohydrate shell to allow
  the bioactive iron to enter macrophages of the
  liver, spleen and bone marrow before being
  released. Iron then enters intracellular storage
  (ferritin) or is transferred to plasma
  transferrin for incorporation into hemoglobin.

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Feraheme? / ferumoxytol Drug Facts

• Pharmacokinetics

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Feraheme? / ferumoxytol Drug Interactions

• Drug Interactions
• Drug-drug interaction studies were not conducted.
• Feraheme may reduce the absorption of
  concomitantly administered oral iron.

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Feraheme? / ferumoxytol Adverse Effects

• Common Adverse Effects

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Feraheme? / ferumoxytol Adverse Effects

• Serious Adverse Effects
• Hypersensitivity reactions, including
  anaphylaxis, were reported in 0.2 (3 / 1,726) of
  subjects receiving Feraheme

9
Feraheme? / ferumoxytol Monitoring Parameters

• Efficacy Monitoring
• Monitor hemoglobin, serum ferritin, serum iron,
  transferrin saturation at least 1 month following
  the second injection.
• Toxicity Monitoring
• Observe patients for signs and symptoms of
  hypersensitivity for at least 30 minutes
  following injection.
• Monitor for hypotension after injection

10
Feraheme? / ferumoxytol Prescription Information

• Dosing
• Initial 510 mg intravenous injection followed by
  a second 510 mg intravenous injection 3 to 8 days
  later
• Cost

1 www.feraheme.com 2 AWP Source Cardinal Health
Pharmaceutical Distribution
11
Feraheme? / ferumoxytol Trial Information

• Ferumoxytol for Treating Iron Deficiency Anemia
  in CKD
• Objective
• Compare efficacy of ferumoxytol to oral iron in
  patients with CKD who are not on dialysis
• Trial Design
• Open-label, randomized, controlled, multicenter
  Phase III trial
• Included 304 patients randomly assigned in a 31
  ratio to IV ferumoxytol or oral iron to maximize
  exposure for safety assessments

Spinowitz BS. J Am Soc Nephrol 2008191599-1605
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Feraheme? / ferumoxytol Trial Information

• Inclusion Criteria
• Anemic adult patients gt 18 years old
• CKD stages 1 to 5
• Hemoglobin lt 11.0 g/dl
• Serum ferritin lt 600 ng/ml
• TSAT lt 30

Spinowitz BS. J Am Soc Nephrol 2008191599-1605
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Feraheme? / ferumoxytol Trial Information

• Exclusion Criteria
• Pregnancy or breastfeeding
• Causes of anemia other than iron deficiency
• Malignancy (except nonmelanoma skin cancer)
• Use of another investigational drug or device
  within 30 days
• Recent iron therapy
• Serum parathyroid hormone gt 1500 ng/L
• Active or recent bleeding
• Recent (or anticipated) surgery other than
  vascular access surgery
• Recent (or anticipated) blood transfusion
• Active infection requiring therapy
• Allergy to intravenous iron
• Allergy to two or more drugs

Spinowitz BS. J Am Soc Nephrol 2008191599-1605
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Feraheme? / ferumoxytol Trial Information

• Intervention
• Two 510 mg doses of intravenous ferumoxytol
  within 5 3 days
• At a rate of 1 mL/sec in the outpatient office
• 200 mg elemental oral iron daily
• As Ferro-Sequels (50 mg of ferrous fumarate plus
  docusate sodium) two tablets twice daily on an
  empty stomach
• Treatment duration
• 21 days

Spinowitz BS. J Am Soc Nephrol 2008191599-1605
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Feraheme? / ferumoxytol Trial Information

• Primary Efficacy Endpoint
• Increase in hemoglobin at day 35
• Other Efficacy Endpoints
• Mean change in ferritin
• Proportion of patients achieving a gt 1 g/dL
  increase in hemoglobin

Spinowitz BS. J Am Soc Nephrol 2008191599-1605
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Feraheme? / ferumoxytol Trial Information
Primary Efficacy Endpoint
Spinowitz BS. J Am Soc Nephrol 2008191599-1605
17
Feraheme? / ferumoxytol Trial Information
Spinowitz BS. J Am Soc Nephrol 2008191599-1605
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Feraheme? / ferumoxytol Trial Information

• Summary of Adverse Events

Spinowitz BS. J Am Soc Nephrol 2008191599-1605
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Feraheme? / ferumoxytol Trial Information

• Treatment-related Adverse Events

Spinowitz BS. J Am Soc Nephrol 2008191599-1605
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Feraheme? / ferumoxytol Trial Information

• Trial Conclusions
• Intravenous therapy is more effective than oral
  iron for increasing hemoglobin levels
• Correction of iron deficiency with intravenous
  iron is an appropriate first step in anemia
  management, before initiating ESA therapy

Spinowitz BS. J Am Soc Nephrol 2008191599-1605
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Feraheme? / ferumoxytol Summary

• Feraheme? (ferumoxytol injection) consists of a
  superparamagnetic iron oxide as an iron
  replacement indicated for the treatment of iron
  deficiency anemia in adult patients with chronic
  kidney disease.
• Ferumoxytol significantly increases hemoglobin,
  both in patients on Erythropoietin Stimulating
  Agents (ESA) and not on ESA, compared to oral
  iron.
• Advantages of ferumoxytol over other intravenous
  iron formulations available on the market include
  lower incidence of anaphylaxis and the potential
  administration of larger doses, reducing office
  visits.

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Feraheme? / ferumoxytol References

• http//www.feraheme.com
• Feraheme package insert. AMAG Pharmaceuticals,
  Inc. June 2009.
• Spinowitz BS. Ferumoxytol for Treating Iron
  Deficiency Anemia in CKD. J Am Soc Nephrol
  2008191599-1605.
• LexiComp Online. Accessed September 22, 2009.
• Facts and Comparisons (eFacts). Accessed
  September 22, 2009.