PK Studies

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Jivi® rFVIII levels remain elevated and sustained over time

  • The pharmacokinetics (PK) of Jivi® were investigated in 29 severe hemophilia A patients (≥12 years of age) following a single 60 IU/kg dose
  • Pharmacokinetics is the activity of drugs in the body over a period of time

PK was primarily measured by*

  • Clearance—the speed at which a drug is removed from the body
  • Area under the curve—the total amount of a drug that reaches the bloodstream, measured by plasma concentration, over time
  • Half-life—the amount of time that it takes for the concentration of a drug to be reduced by half; used to determine how long a drug remains active in the body

Jivi® is a PEGylated rFVIII with an extended half-life§ of

What is PEGylation used for?

  • PEGylation increases the amount of time a medicine may stay active in the body (half-life)

Does PEG accumulate in the body?

  • There was no evidence of PEG accumulation in the plasma of patients in the Jivi® clinical trial
  • Our bodies have known mechanisms for removing PEG.
    It is excreted through both the kidneys (to urine) and the liver (to feces)
  • IU, international units; kg, kilograms; PEG, polyethylene glycol; rFVIII, recombinant Factor VIII.
  • Other PK parameters measured were maximum drug concentration in plasma after a single dose, mean residence time after an IV administration, and apparent volume of distribution at steady state.
  • Clearance measured 1.63 mL/h/kg.
  • Area under the curve measured 4060 IU*h/dL.
  • Half-life is defined as the time it takes for the amount of a drug in the blood to decrease by one half.
  • With a single, 60 IU/kg dose.

Jivi® vs Eloctate® PK comparison

  • Jivi® and Eloctate® compared PK parameters in a crossover study of 18 male patients aged 18-65 with severe hemophilia A. Patients were each given a single dose of either Jivi® or Eloctate®, then halfway through the study, following a washout, patients switched to a single dose of the other treatment
  • One patient with preexisting anti-PEG antibodies had significantly different PK results. This patient was determined to be an outlier. Including this outlier patient in the analysis (N=18), there were no PK differences observed. The outlier patient was excluded from further analysis

Jivi® vs Eloctate® PK Comparison

In the 17 patients (excluding the outlier), there were 3 statistically significant PK differences:

Compared with Eloctate®

  • Jivi® gave patients a HIGHER AMOUNT of medication available for clotting over time*
  • Jivi® REMAINED LONGER in the body
  • Jivi® had a LONGER HALF-LIFE

Jivi® demonstrated more time before reaching minimum FVIII levels

Jivi® median time to minimum FVIII levels (compared to Eloctate®) in a population PK analysis (excluding the outlier patient, N=17)§

  • PK, pharmacokinetics; FVIII, factor VIII.
  • Jivi® had a higher mean area under the curve (+25%).
  • Jivi® had lower mean clearance (-20%).
  • Jivi® had a longer mean half-life (+7%).
  • Adapted from Shah et al. A population PK model was developed based on data obtained by a one-stage assay to simulate time to reach FVIII thresholds of 1, 3, 5, and 10% FVIII.

Compared with Eloctate®, Jivi® demonstrated statistically significantly (N=17):

For N=18 patients, including the PK outlier patient, Jivi® demonstrated noninferiority to Eloctate® for AUC(0-tlast)*

Ask your doctor if Jivi®
is right for you.
  • PK, pharmacokinetics; FVIII, factor VIII.
  • Jivi® had a higher mean area under the curve (+25%).
  • Jivi® had lower mean clearance (-20%).
  • Jivi® had a longer mean half-life (+7%).
  • 10%: 63 hours on Jivi® vs 52 hours on Eloctate®; 5%: 79 hours on Jivi® vs 67 hours on Eloctate®; 3%: 91 hours on Jivi® vs 79 hours on Eloctate®; 1%: 117 hours on Jivi® vs 104 hours on Eloctate®.
  • PK, pharmacokinetics.