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The European Commission (EC) has granted marketing authorization for vonicog alfa (Veyvondi), a recombinant von Willebrand factor (rVWF) product.
The EC approved vonicog alfa for the treatment of bleeding events and treatment/prevention of surgical bleeding in adults (age 18 and older) with von Willebrand disease (VWD) when desmopressin treatment alone is ineffective or not indicated.
The approval means Shire is authorized to market vonicog alfa in the European Union as well as in Iceland, Lichtenstein, and Norway.
The EC’s approval of vonicog alfa was based on outcomes from three clinical trials. This includes a phase 1 study and a pair of phase 3 trials—one in a surgical setting and one in a non-surgical setting.
Data from these studies are available in the Summary of Product Characteristics for vonicog alfa.
Phase 1 trial
This trial (NCT00816660, 070701) enrolled patients with type 3 or severe type 1 VWD.
The goal was to assess the safety and pharmacokinetics of vonicog alfa (rVWF) combined at a fixed ratio with recombinant factor VIII (rFVIII)—referred to as “rVWF-rFVIII.” The researchers compared rVWF-rFVIII to plasma-derived (pd) VWF combined with pdFVIII (pdVWF-pdFVIII).
The safety analysis included 32 patients who received rVWF-rFVIII. There were no thrombotic events, serious adverse events, or new cases of inhibitors to VWF or FVIII in these patients.
The pharmacokinetic analysis included 19 patients. The researchers said the pharmacokinetics of rVWF ristocetin cofactor activity, VWF antigen, and collagen-binding activity were similar with rVWF-rFVIII and pdVWF-pdFVIII.
FVIII levels were higher after infusion with rVWF-rFVIII than with pdVWF-pdFVIII, even after 72 hours. The researchers said this suggests that rVWF alone “could maintain sufficient FVIII activity to treat a bleeding episode once the initial FVIII level has reached a therapeutic threshold.”
These results were published in Blood in 2013.
Phase 3: Non-surgical
This study (NCT01410227, 071001) included 49 patients with VWD who received vonicog alfa with or without rFVIII.
All participants had successful treatment of bleeding episodes. Most (96.9%) treated bleeds (192 bleeds in 22 patients) were given an “excellent” efficacy rating (as good as or better than expected).
Most bleeds (81.8%) were resolved with a single infusion of vonicog alfa, and the treatment had a mean half-life of 21.9 hours.
There were 8 adverse events considered related to vonicog alfa, and 2 were serious. One patient experienced 2 simultaneous serious events—chest discomfort and increased heart rate—but these were resolved.
There were no thrombotic events in this trial, no treatment-related binding or neutralizing antibodies against VWF, and no neutralizing antibodies against FVIII.
These results were published in Blood in 2015.
Phase 3: Surgical setting
This trial (NCT02283268, 071101) enrolled 15 adults with severe VWD who were undergoing elective surgical procedures (10 of them major procedures).
Patients received vonicog alfa at 40 to 60 IU per kg of body weight 12 to 24 hours before surgery. Within 3 hours of surgery, each patient’s FVIII level (FVIII:C) was assessed, with a target of 30 IU/dL for minor surgeries and 60 IU/dL for major surgeries.
Within an hour of surgery, patients received a dose of vonicog alfa, with or without rFVIII, depending on the target FVIII:C levels at the 3-hour assessment.
Ten patients received rVWF alone, 12 did not receive any preoperative FVIII, and 2 did not receive rVWF postoperatively.
Vonicog alfa demonstrated overall hemostatic efficacy, as assessed 24 hours after the last perioperative infusion or the completion of the study visit, whichever occurred earlier.
Intra- and post-operative hemostasis was rated as “excellent” (as good as or better than expected) in 60% of patients and “good” (probably as good as expected) in 40% of patients.
One patient developed deep vein thrombosis 3 days after undergoing hip replacement surgery.
One patient tested positive for binding antibodies to VWF. None of the patients developed binding antibodies against potential impurities such as rFurin, CHO-protein, or mouse IgG.
These results were presented at the WFH 2018 World Congress.
The European Commission (EC) has granted marketing authorization for vonicog alfa (Veyvondi), a recombinant von Willebrand factor (rVWF) product.
The EC approved vonicog alfa for the treatment of bleeding events and treatment/prevention of surgical bleeding in adults (age 18 and older) with von Willebrand disease (VWD) when desmopressin treatment alone is ineffective or not indicated.
The approval means Shire is authorized to market vonicog alfa in the European Union as well as in Iceland, Lichtenstein, and Norway.
The EC’s approval of vonicog alfa was based on outcomes from three clinical trials. This includes a phase 1 study and a pair of phase 3 trials—one in a surgical setting and one in a non-surgical setting.
Data from these studies are available in the Summary of Product Characteristics for vonicog alfa.
Phase 1 trial
This trial (NCT00816660, 070701) enrolled patients with type 3 or severe type 1 VWD.
The goal was to assess the safety and pharmacokinetics of vonicog alfa (rVWF) combined at a fixed ratio with recombinant factor VIII (rFVIII)—referred to as “rVWF-rFVIII.” The researchers compared rVWF-rFVIII to plasma-derived (pd) VWF combined with pdFVIII (pdVWF-pdFVIII).
The safety analysis included 32 patients who received rVWF-rFVIII. There were no thrombotic events, serious adverse events, or new cases of inhibitors to VWF or FVIII in these patients.
The pharmacokinetic analysis included 19 patients. The researchers said the pharmacokinetics of rVWF ristocetin cofactor activity, VWF antigen, and collagen-binding activity were similar with rVWF-rFVIII and pdVWF-pdFVIII.
FVIII levels were higher after infusion with rVWF-rFVIII than with pdVWF-pdFVIII, even after 72 hours. The researchers said this suggests that rVWF alone “could maintain sufficient FVIII activity to treat a bleeding episode once the initial FVIII level has reached a therapeutic threshold.”
These results were published in Blood in 2013.
Phase 3: Non-surgical
This study (NCT01410227, 071001) included 49 patients with VWD who received vonicog alfa with or without rFVIII.
All participants had successful treatment of bleeding episodes. Most (96.9%) treated bleeds (192 bleeds in 22 patients) were given an “excellent” efficacy rating (as good as or better than expected).
Most bleeds (81.8%) were resolved with a single infusion of vonicog alfa, and the treatment had a mean half-life of 21.9 hours.
There were 8 adverse events considered related to vonicog alfa, and 2 were serious. One patient experienced 2 simultaneous serious events—chest discomfort and increased heart rate—but these were resolved.
There were no thrombotic events in this trial, no treatment-related binding or neutralizing antibodies against VWF, and no neutralizing antibodies against FVIII.
These results were published in Blood in 2015.
Phase 3: Surgical setting
This trial (NCT02283268, 071101) enrolled 15 adults with severe VWD who were undergoing elective surgical procedures (10 of them major procedures).
Patients received vonicog alfa at 40 to 60 IU per kg of body weight 12 to 24 hours before surgery. Within 3 hours of surgery, each patient’s FVIII level (FVIII:C) was assessed, with a target of 30 IU/dL for minor surgeries and 60 IU/dL for major surgeries.
Within an hour of surgery, patients received a dose of vonicog alfa, with or without rFVIII, depending on the target FVIII:C levels at the 3-hour assessment.
Ten patients received rVWF alone, 12 did not receive any preoperative FVIII, and 2 did not receive rVWF postoperatively.
Vonicog alfa demonstrated overall hemostatic efficacy, as assessed 24 hours after the last perioperative infusion or the completion of the study visit, whichever occurred earlier.
Intra- and post-operative hemostasis was rated as “excellent” (as good as or better than expected) in 60% of patients and “good” (probably as good as expected) in 40% of patients.
One patient developed deep vein thrombosis 3 days after undergoing hip replacement surgery.
One patient tested positive for binding antibodies to VWF. None of the patients developed binding antibodies against potential impurities such as rFurin, CHO-protein, or mouse IgG.
These results were presented at the WFH 2018 World Congress.
The European Commission (EC) has granted marketing authorization for vonicog alfa (Veyvondi), a recombinant von Willebrand factor (rVWF) product.
The EC approved vonicog alfa for the treatment of bleeding events and treatment/prevention of surgical bleeding in adults (age 18 and older) with von Willebrand disease (VWD) when desmopressin treatment alone is ineffective or not indicated.
The approval means Shire is authorized to market vonicog alfa in the European Union as well as in Iceland, Lichtenstein, and Norway.
The EC’s approval of vonicog alfa was based on outcomes from three clinical trials. This includes a phase 1 study and a pair of phase 3 trials—one in a surgical setting and one in a non-surgical setting.
Data from these studies are available in the Summary of Product Characteristics for vonicog alfa.
Phase 1 trial
This trial (NCT00816660, 070701) enrolled patients with type 3 or severe type 1 VWD.
The goal was to assess the safety and pharmacokinetics of vonicog alfa (rVWF) combined at a fixed ratio with recombinant factor VIII (rFVIII)—referred to as “rVWF-rFVIII.” The researchers compared rVWF-rFVIII to plasma-derived (pd) VWF combined with pdFVIII (pdVWF-pdFVIII).
The safety analysis included 32 patients who received rVWF-rFVIII. There were no thrombotic events, serious adverse events, or new cases of inhibitors to VWF or FVIII in these patients.
The pharmacokinetic analysis included 19 patients. The researchers said the pharmacokinetics of rVWF ristocetin cofactor activity, VWF antigen, and collagen-binding activity were similar with rVWF-rFVIII and pdVWF-pdFVIII.
FVIII levels were higher after infusion with rVWF-rFVIII than with pdVWF-pdFVIII, even after 72 hours. The researchers said this suggests that rVWF alone “could maintain sufficient FVIII activity to treat a bleeding episode once the initial FVIII level has reached a therapeutic threshold.”
These results were published in Blood in 2013.
Phase 3: Non-surgical
This study (NCT01410227, 071001) included 49 patients with VWD who received vonicog alfa with or without rFVIII.
All participants had successful treatment of bleeding episodes. Most (96.9%) treated bleeds (192 bleeds in 22 patients) were given an “excellent” efficacy rating (as good as or better than expected).
Most bleeds (81.8%) were resolved with a single infusion of vonicog alfa, and the treatment had a mean half-life of 21.9 hours.
There were 8 adverse events considered related to vonicog alfa, and 2 were serious. One patient experienced 2 simultaneous serious events—chest discomfort and increased heart rate—but these were resolved.
There were no thrombotic events in this trial, no treatment-related binding or neutralizing antibodies against VWF, and no neutralizing antibodies against FVIII.
These results were published in Blood in 2015.
Phase 3: Surgical setting
This trial (NCT02283268, 071101) enrolled 15 adults with severe VWD who were undergoing elective surgical procedures (10 of them major procedures).
Patients received vonicog alfa at 40 to 60 IU per kg of body weight 12 to 24 hours before surgery. Within 3 hours of surgery, each patient’s FVIII level (FVIII:C) was assessed, with a target of 30 IU/dL for minor surgeries and 60 IU/dL for major surgeries.
Within an hour of surgery, patients received a dose of vonicog alfa, with or without rFVIII, depending on the target FVIII:C levels at the 3-hour assessment.
Ten patients received rVWF alone, 12 did not receive any preoperative FVIII, and 2 did not receive rVWF postoperatively.
Vonicog alfa demonstrated overall hemostatic efficacy, as assessed 24 hours after the last perioperative infusion or the completion of the study visit, whichever occurred earlier.
Intra- and post-operative hemostasis was rated as “excellent” (as good as or better than expected) in 60% of patients and “good” (probably as good as expected) in 40% of patients.
One patient developed deep vein thrombosis 3 days after undergoing hip replacement surgery.
One patient tested positive for binding antibodies to VWF. None of the patients developed binding antibodies against potential impurities such as rFurin, CHO-protein, or mouse IgG.
These results were presented at the WFH 2018 World Congress.