There are three C1-inhibitor drug candidates vying for FDA approval in hereditary angiodema (HAE). All three are in the running for acute treatment of HAE attacks, but only one of them (Cinryze from LEVP) is in line for approval as a prophylactic.
The key distinguishing attribute is the half-life, which is shown below. (These numbers are means; there is considerable variation from patient to patient.)
Rhucin is a recombinant drug produced in transgenic rabbits. As is the case with GTCB’s ATryn, Rhucin’s half-life is shorter than the corresponding endogenous protein due to differences in glycosylation. A short half-life is typically an advantage in an acute-care setting, but a half life of only three hours makes Rhucin totally unsuitable for prophylactic use.
LEVP is seeking approval of Cinryze as a prophylactic (#msg-28988139); the 48-hour half-life makes this doable insofar as patients can probably get by with two infusions per week.
Berinert’s 39.5-hour half-life is only about 20% shorter than the half-life of Cinryze. A 20% difference might not seem like a big deal on first glance, but it is a big deal because C1-inhibitors, as presently formulated, must be administered by IV and Berinert’s half-life would probably necessitate three infusions per week vs Cinryze’s two. Consequently, CSL Behring is not seeking FDA approval as a prophylactic.
Why does Berinert have a shorter half-life than Cinryze since they are the same protein and both are derived from human plasma? The difference in half-life probably stems from the processing to remove pathogens: Berinert uses pasteurization while Cinryze uses nano-filtration. Pasteurization presumably alters the C1-inh molecule in a way that speeds metabolism.
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