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Single-chain Design Helps
AFSTYLA Bind More Tightly to
VWF1

Unique mechanism of action
(MOA) leads to increased
stability and long-lasting
protection

Like naturally occurring Factor VIII, AFSTYLA binds to von Willebrand factor (VWF), which helps protect it from degradation in circulation.

AFSTYLA is the first and only recombinant Factor VIII with a single-chain design

  • Heavy and light chains of Factor VIII are covalently bonded into a single-chain structure.
  • This allows increased binding affinity to VWF, protecting AFSTYLA from degradation in circulation.
The novel single-chain design allows tighter binding between AFSTYLA and VWF

Enhanced VWF affinity extends time in circulation2,3

In the AFSTYLA Phase 1 PK study:

  • Overall, the clearance of AFSTYLA was lower than that of the active comparator
  • In patients treated with AFSTYLA, the reduction in clearance trended highest in subjects with low VWF
Relationship between VWF and clearance of Factor VIII in patients 18-65 years* chart

Clearance is mathematically related to other pharmacokinetic measures, such as half-life and area under the curve—important parameters that are considered when determining optimal dosing regimens.

*Study details

Samples from 27 adult patients were analyzed for predose VWF and clearance of Factor VIII after a single 50 IU/kg infusion of AFSTYLA and active comparator (with washout period). Regression lines estimated from a post hoc analysis are shown. 95% CI=95% confidence interval.2,3

References: 1. Zollner S, Raquet E, Claar P, et al. Non-clinical pharmacokinetics and pharmacodynamics of
rVlll-SingleChain, a novel recombinant single-chain factor VIII. Thromb Res. 2014;134(1):125-131. 2. Data on
file. Available from CSL Behring as DOF AFS-002. 3. Klamroth R, Simpson M, von Depka-Prondzinski M, et al.
Comparative pharmacokinetics of rVlll-SingleChain and octocog alfa (Advate®) in patients with severe
haemophilia A. Haemophilia. 2016;22(5):730-738.

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