Table 1.
Recombinant coagulation factor VIII products approved for Hemophilia A treatment.
| Product | Company | Generation | Cell line | Main characteristics | Approval year |
|---|---|---|---|---|---|
| Recombinate® | Genetics Insitute/Baxter | 1 | CHO | Full‐length | 1992, FDA |
| (also market as Bioclate® by Aventis Behring) | (Currently Shire-Baxalta) | mAb (murine hybridome) –affinity chromatography | |||
| Human albumin as stabilizer | |||||
| t1/2=14.6h | |||||
| Kogenate® | Bayer | 1 | BHK | Full-length | 1993, FDA |
| (also market as Helixate® by Aventis-Behring) | mAb (murine hybridome) - affinity chromatography | ||||
| Human albumin as stabilizer | |||||
| t1/2=12h | |||||
| Refacto® | Wyeth | 2 | CHO | B-domain deleted | 1998, EMA |
| mAb (murine hybridome) - affinity chromatography | 2000, FDA | ||||
| Sucrose as stabilizer | |||||
| t1/2=14.8h | |||||
| Kogenate® FS | Bayer | 2 | BHK | Full-length | 2000, FDA |
| (also market as Helixate® FS by Aventis-Behring) | mAb (murine hybridome) - affinity chromatography | ||||
| Sucrose as stabilizer | |||||
| t1/2=12h | |||||
| Advate® | Baxter | 3 | CHO | Full-length | 2004, EMA |
| mAb (murine hybridome)-based affinity chromatography | 2007, FDA | ||||
| Trehalose and mannitol as stabilizer | |||||
| t1/2=13h | |||||
| Refacto® AF | Pfizer | 3 | CHO | B-domain deleted | 2008, FDA |
| (also market as Xyntha outside EU) | polypeptide ligand-based affinity chromatography | ||||
| Sucrose as stabilizer | |||||
| t1/2=11-12h | |||||
| Novoeight® | Novo Nordisk | 3 | CHO | B-domain truncated | 2013, EMA |
| mAb -based affinity chromatography | |||||
| Sucrose as stabilizer | |||||
| t1/2=11-12h | |||||
| Adynovate® | Shire-Baxalta | 3 | CHO | Full-length, Pegylated | 2015, FDA |
| mAb-based affinity chromatography | |||||
| Trehalose and mannitol as stabilizer | |||||
| t1/2=13.4-14.7h | |||||
| Afstyla® | CSL Behring | 3 | CHO | B-domain truncated single chain protein | 2016, FDA |
| mAb-based affinity chromatography | |||||
| Sucrose as stabilizer | |||||
| t1/2=14.2-14.3h | |||||
| Eloctate® | Biogen Idec | 4 | Hek-293 | B-deleted FVIII-Fc fusion protein (IgG1) | 2014, FDA |
| Recombinant protein (produced in S. cerevisiae)-based affinity chromatography | |||||
| Sucrose as stabilizer | |||||
| t1/2=19h | |||||
| Nuwiq® | Octapharma AG | 4 | Hek-293 | B-domain deleted | 2014, EMA |
| Recombinant Ab fragment (produced in S. cerevisiae)-based affinity chromatography | 2015, FDA | ||||
| Sucrose as stabilizer | |||||
| t1/2=15h | |||||
| Kovaltry® | Bayer | 3 | BHK expressing HSP 70 | Full-lengthpeptide ligand-based affinity chromatography | 2016, FDA |
| Sucrose as stabilizer | |||||
| t1/2=13-14h |
Abbreviations: CHO – Chinese Hamster Ovary cells; BHK – Baby Hamster Kidney cells; Hek-293; Human Embryonic Kidney cells; HSP 70 – heat shock protein 70.