Many factor VIII products available in the treatment of hemophilia A: an embarrassment of riches?

Figures & data

Table 1 Available FVIII products

Generation	Products	FVIII	Technology	Half-life*	Date of US FDA approval
Plasma derived	Antihemophilic factor (Hemofil M^®, Koate- DVI^®, Monarc-M^®, Monoclate-P^®)	Full length	Pooled human plasma	14.8–17.5 hours	1966 (Hemofil M), 1974 (Koate-DVI)
Plasma derived/VWF complex	Antihemophilic factor/VWF complex (Alphanate^®, Humate-P^®, Wilate^®)	Full length with VWF	Pooled human plasma	12.2–17.9 hours	1978 (Alphanate), 1986 (Humate-P), August 2009 (Wilate)
Recombinant: first generation	Antihemophilic factor recombinant (Recombinate^®)	Full length	BSA in culture and human albumin as stabilizer	14.6 ± 4.9 hours	December 1992
Recombinant: second generation	rFVIII-FS (Helixate^®, Kogenate^®)	Full length	Human plasma protein solution in culture	13.74 hours	June 2000
Recombinant: third generation	Antihemophilic factor recombinant (Advate^®, Kovaltry^®)	Full length	No human or animal protein added	12–14.2 hours	July 2003 (Advate), March 2016 (Kovaltry)
Recombinant: second generation	Moroctocog alfa (ReFacto^®)	BDD	Human plasma protein solution in culture	14.5 ± 5.3 hours	March 2000
Recombinant: third generation	Moroctocog alfa (Xyntha^®), Turoctocog alfa (Novoeight^®)	BDD	No human or animal protein added	10.8–12 hours	February 2008 (Xyntha), October 2013 (Novoeight)
Recombinant: fourth generation	Simoctocog alfa (Nuwiq^®)	BDD	HEK cells to allow human glycosylation	17.1 ± 11.2 hours	September 2015
Recombinant: third-generation EHL	Octocog alfa pegol (Adynovate^®)	BDD-PEGylated	PEGylation to parent drug Advate	14.69 ± 3.79 hours	December 2016
Recombinant: fourth-generation EHL	rFVIII–Fc (Eloctate^®)	BDD-rFVIII–Fc	HEK cells to allow human glycosylation	19.7 ± 2.3 hours	June 2014
Recombinant: third-generation EHL	rFVIII-SC (Afstyla^®)	EHL single chain	No human or animal protein added	14.2 hours	May 2016

Note:

* The half-life of the different factors was taken from the product brochures from the manufacturers and differs in how it was determined.

Abbreviations: FVIII, factor VIII; US FDA, US Food and Drug Administration; VWF, Von Willebrand factor; BSA, bovine serum albumin; rFVIII, recombinant factor VIII; BDD, B domain deleted; HEK, human embryonic kidney; EHL, extended half-life; PEG, polyethylene glycol; SC, single chain; rFVIII-FS, recombinant FVIII formulated with sucrose; rFVIII-Fc, antihemophilic factor (recombinant), Fc fusion protein; rFVIII-SC, antihemophilic factor (recombinant), single chain.

Table 2 FVIII products in development

Generation	Products	FVIII	Technology	Half-life (h)
Recombinant: third-generation EHL	BAY94-9027	BDD-PEGylated	Site-specific addition of PEG side chain	13.7–28.1
Recombinant: third-generation EHL	N8-GP	BD-modified glycoPEGylated	GlycoPEGylated addition to FVIII	18.4–19.04
Novel bispecific antibody	Emicizumab	None	Bispecific antibody with FVIII-mimetic function	Weeks

Abbreviations: FVIII, factor VIII; EHL, extended half-life; BDD, B domain deleted; PEG, polyethylene glycol.