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.