What is Xyntha (Recombinant Factor VIII)?
Xyntha is a recombinant factor VIII concentrate used for replacement therapy in patients with hemophilia A, manufactured without human-derived plasma proteins during purification and formulation, providing effective hemostatic control for bleeding episodes and prophylaxis. 1, 2
Product Classification and Manufacturing
Xyntha belongs to the category of recombinant factor VIII products engineered from mammalian cell culture systems using recombinant DNA technology, distinguishing it from plasma-derived factor VIII concentrates. 1 These recombinant products are manufactured without pooled human plasma, thereby eliminating the risk of transmission of blood-borne pathogens present in plasma-derived products. 1
Clinical Indications
Primary Use in Hemophilia A
Xyntha is indicated for replacement therapy in patients with hemophilia A (factor VIII deficiency), which affects approximately 1 in 10,000 males and accounts for 80-85% of all hemophilia cases. 1, 3
The product is used both prophylactically to prevent bleeding episodes and therapeutically to control active bleeding in patients with severe hemophilia A (factor VIII levels <1 IU/dL). 2, 1
Treatment Applications
For prophylaxis, standard half-life recombinant factor VIII products like Xyntha typically require dosing 3 times weekly to maintain adequate trough levels and prevent spontaneous joint and muscle bleeding. 2
For therapeutic use, Xyntha provides excellent hemostatic control, with 73.9-93.5% of bleeding episodes requiring only one to two infusions for resolution. 3, 4
The product is effective for managing bleeding during major surgical procedures, with excellent hemostasis documented in clinical trials. 3
Safety Profile
Infectious Disease Risk
Recombinant factor VIII products like Xyntha eliminate the risk of lipid-enveloped virus transmission (hepatitis B, hepatitis C, HIV) and minimize the small risk of non-enveloped virus transmission (hepatitis A, parvovirus B19) compared to plasma-derived products. 1
This makes recombinant products the preferred choice for plasma-naïve patients, particularly pediatric patients with newly diagnosed severe hemophilia A. 1
Inhibitor Development
The most significant complication is the development of neutralizing alloantibodies (inhibitors), which occur in 20-35% of patients with severe hemophilia A, though de novo inhibitor formation in previously treated patients is rare (approximately 1%). 1, 3
In previously untreated patients, inhibitor development rates are higher, with clinical trials showing inhibitor formation in approximately 6 of 21 children, though most had low-level inhibitors that did not preclude continued treatment. 3
Tolerability
- Recombinant factor VIII products demonstrate excellent tolerability, with only 0.27% of infusions associated with drug-related adverse events, most of which are mild or moderate. 4
Clinical Efficacy
Pharmacokinetics
The in vivo recovery and elimination half-lives of recombinant factor VIII equal or exceed those of plasma-derived factor VIII, with a typical half-life allowing for dosing every 8-24 hours for therapeutic use. 3, 1
Standard half-life products require more frequent dosing compared to extended half-life formulations, which can reduce dosing frequency to potentially once weekly. 2
Hemostatic Control
Clinical trials demonstrate that recombinant factor VIII provides biologic activity comparable to plasma-derived factor VIII, with 80.5% of bleeding responses rated as excellent or good. 3, 4
The projected annual consumption of recombinant factor VIII is similar to that of plasma-derived concentrates, indicating comparable efficacy. 3
Important Clinical Considerations
Recombinant factor VIII products are considered interchangeable with respect to clinical efficacy in controlling bleeding, making price and inhibitor risk the main determinants of product selection. 5
For patients who develop inhibitors, bypassing agents (recombinant activated factor VII or activated prothrombin complex concentrates) or emicizumab become necessary, as standard factor VIII replacement becomes ineffective. 2, 1
The availability of recombinant products has raised the life expectancy of patients with hemophilia A in high-income countries to that of males in the general population. 5