Jivi has been designed to ensure full function of the FVIII protein, while increasing levels of FVIII over time.1
• 60 kDa branched (2 x 30 kDa) PEG attached to a cysteine that has been introduced into the A3 domain (K1804C), maintaining FVIII function1,2
• PEG:FVIII ratio of 1:1 (single PEGylation site)2
PEG, polyethylene glycol.
PEG, polyethylene glycol.
Get the answers to commonly asked questions about PEG, including information on PEGylation of rFVIII
PEGs, short for polyethylene glycols, are synthetic, highly water soluble, inert polymers consisting of repetitive units of ethylene glycol (sometimes described as ‘ethylene oxide’), collectively known as PEG.1-3
In addition to a long history of use in the cosmetic and food industries,5,6 PEG is used as an excipient in viral vaccine formulations – minimizing their reliance on cold-chain supply.7,8
Jivi has one 60-kDa PEG (2 x 30-kDa branched PEG) attached via a maleimide linker to a cysteine amino acid (K1804C) in the A3 domain introduced by site-directed mutagenesis (i.e. site-specifically PEGylated).9-11
The A3 domain was chosen through extensive testing of variants with PEG attached in each of five domains. K1804C was selected for retention of von Willebrand factor binding, coagulation function, manufacturing efficacy and improved PK vs. rFVIII-FS.11
The 60-kDa PEG size was chosen instead of the small PEG molecules (e.g. 12, 20, or 30 kDa) evaluated by Bayer because it yielded improved pharmacokinetics (e.g. longer half-life, slower clearance) while preserving full biological activity of FVIII.11,12
PK, pharmacokinetic.