FDA approves first coagulation factor-albumin fusion protein to treat patients with hemophilia B.

March 4, 2016

dt_141028_hemophilia_800x600The U.S. Food and Drug Administration approved Idelvion, Coagulation Factor IX (Recombinant), Albumin Fusion Protein, for use in children and adults with Hemophilia B.

Idelvion is the first coagulation factor-albumin fusion protein product to be approved, and the second Factor IX fusion protein product approved in the U.S. that is modified to last longer in the blood

DESCRIPTION

  • IDELVION, Coagulation Factor IX (Recombinant), Albumin Fusion Protein (rIX-FP).
  • The active ingredient in IDELVION, recombinant human coagulation Factor IX albumin fusion protein is a purified protein produced by recombinant DNA technology.
  • It is generated by the genetic fusion of recombinant albumin to recombinant coagulation Factor IX. The genetic fusion of the cDNA of human albumin to the cDNA of human coagulation Factor IX enables the gene product to be expressed as a single recombinant protein designated as rIX-FP.
  • The Factor IX portion of IDELVION is identical to the Thr148 allelic form of human plasma-derived Factor IX.
  • The cleavable linker between the Factor IX and albumin moieties is derived from the endogenous activation peptide in native Factor IX. rIX-FP remains intact in the circulation until Factor IX is activated, whereupon albumin is cleaved from Factor IX, releasing activated Factor IX (FIXa) when it is needed for coagulation.
  • IDELVION is manufactured without the use of proteins derived from human or animal source materials.
  • IDELVION is a glycoprotein consisting of 1018 amino acids secreted by a genetically engineered Chinese hamster ovary (CHO) cell line.
  • The CHO cell line secretes rIX-FP into a defined cell culture medium that does not contain hormones and the rIX-FP protein is purified by a process that does not require the use of a monoclonal antibody reagent.
  • The manufacturing process incorporates three validated virus clearance steps, including virus inactivation by solvent/detergent treatment and virus removal by filtration.
  • The potency expressed in International Units is determined using an in vitro aPTT-based one-stage clotting assay against CSL Behring’s manufacturing reference standard.
  • This internal potency standard has been calibrated against the World Health Organization (WHO) International Standard for Factor IX concentrate by a one-stage clotting assay using synthetic silica and synthetic phospholipid-based reagents.
  • IDELVION is available in single-use vials containing nominally 250, 500, 1000, or 2000 IU of Factor IX formulated with sodium citrate, polysorbate 80, mannitol and sucrose. The actual amount of Factor IX activity in IU is labeled on each vial. After reconstitution of the lyophilized powder, all dosage strengths yield a clear, yellow to colorless solution. IDELVION contains no preservatives.

CLINICAL PHARMACOLOGY

Mechanism of Action

  • IDELVION is a recombinant protein that temporarily replaces the missing coagulation Factor IX needed for effective hemostasis.
  • IDELVION is comprised of genetically fused recombinant coagulation Factor IX and recombinant albumin. Fusion with recombinant albumin extends the half-life of Factor IX.

Pharmacodynamics

  • The administration of IDELVION increases plasma levels of Factor IX and can temporarily correct the coagulation defect in patients.

INDICATIONS AND USAGE

IDELVION, Coagulation Factor IX (Recombinant), Albumin Fusion Protein (rIX-FP), a recombinant human blood coagulation factor, is indicated in children and adults with hemophilia B (congenital Factor IX deficiency) for:

  • On-demand control and prevention of bleeding episodes
  • Perioperative management of bleeding •Routine prophylaxis to prevent or reduce the frequency of bleeding episodes

Limitations of Use: IDELVION is not indicated for immune tolerance induction in patients with Hemophilia B

Dosage

Each vial of IDELVION contains the recombinant Factor IX potency in international units (IU) that is stated on the carton and vial label.

Dosage and duration of treatment with IDELVION depends on the severity of Factor IX deficiency, the location and extent of bleeding, and the patient’s clinical condition, age and recovery of Factor IX.

The calculation of the required dose of IDELVION is based on the empirical finding that one IU of IDELVION per kg body weight is expected to increase the circulating level of Factor IX by 1.3 IU/dL in patients ≥12 years of age and by 1 IU/dL in patients <12 years of age.

The required dose of IDELVION for treatment of bleeding episodes is determined using the following formula:

Required Units (IU) = Body Weight (kg) x Desired Factor IX rise (% of normal or IU/dL) x (reciprocal of recovery (IU/dL per IU/kg))

OR

Increase in Factor IX IU/dL (or % of normal) = Dose (IU) x Recovery (IU/dL per IU/kg)/ body weight (kg)

Adjust the dose based on the individual patient’s clinical condition and response.

2016-03-09

 

Safety and Efficacy

  • The safety and efficacy of Idelvion were evaluated in two multicenter studies, which included a total of 90 adult and pediatric patients with Hemophilia B between 1 and 61 years of age.
  • Idelvion was demonstrated to be effective in controlling bleeding episodes and in managing perioperative bleeding.
  • Idelvion used as prophylaxis led to a significant reduction in the rate of spontaneous bleeding episodes per year despite less frequent infusions of Idelvion.
  • No safety concerns were identified in the studies.

CONTRAINDICATIONS

  • Do not use in patients who have had life-threatening hypersensitivity reactions to IDELVION or its components, including hamster proteins.

WARNINGS AND PRECAUTIONS

  • Hypersensitivity reactions, including anaphylaxis, are possible. Should symptoms occur, discontinue IDELVION and administer appropriate treatment.
  • Development of neutralizing antibodies (inhibitors) to IDELVION may occur. If expected Factor IX plasma recovery in patient plasma is not attained, or if bleeding is not controlled with an appropriate dose, perform an assay that measures Factor IX inhibitor concentration.
  • Thromboembolism (e.g., pulmonary embolism, venous thrombosis, and arterial thrombosis) may occur when using Factor IX-containing products.
  • Nephrotic syndrome has been reported following immune tolerance induction with Factor IX-containing products in hemophilia B patients with Factor IX inhibitors and a history of allergic reactions to Factor IX.
  • Factor IX activity assay results may vary with the type of activated partial thromboplastin time reagent used.

ADVERSE REACTIONS

  • The most common adverse reaction (incidence ≥1%) reported in clinical trials was headache.

Idelvion is manufactured by CSL Behring, headquartered in King of Prussia, Pennsylvania.

References:

FDA News

Prescribing information