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The European Commission has granted Shire marketing authorization for vonicog alfa (Veyvondi), a recombinant von Willebrand factor (rVWF) product.

The European Commission (EC) approved vonicog alfa for the treatment of bleeding events and treatment/prevention of surgical bleeding in adults with von Willebrand disease (VWD) when desmopressin treatment alone is ineffective or not indicated.

The product was approved in the United States in 2015 for on-demand treatment and control of bleeding episodes in adults.

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 nonsurgical setting.

Data from these studies are available in the Summary of Product Characteristics for vonicog alfa.The phase 1 trial (NCT00816660) enrolled patients with type 3 or severe type 1 VWD.

The goal was to assess the safety and pharmacokinetics of vonicog alfa combined at a fixed ratio with recombinant factor VIII – referred to as “rVWF-rFVIII.” The researchers compared rVWF-rFVIII with 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. These results were published in Blood (2013 Aug 1;122[5]:648-57).The phase 3 nonsurgical study (NCT01410227) included 49 patients with VWD who received vonicog alfa with or without rFVIII.

All participants had successful treatment of bleeding episodes. Nearly all (96.9%) treated bleeds were given an “excellent” efficacy rating and most (81.8%) were resolved with a single infusion of vonicog alfa; the treatment had a mean half-life of 21.9 hours.

There were eight adverse events considered related to vonicog alfa, two of which were serious. There were no thrombotic events, no treatment-related binding or neutralizing antibodies against VWF, and no neutralizing antibodies against FVIII. These results were published in Blood (2015 Oct 22;126[17]:2038-46).

The phase 3 surgical trial (NCT02283268) enrolled 15 adults with severe VWD who were undergoing elective surgical procedures.
 

 

Patients received vonicog alfa at 40-60 IU per kg of body weight 12-24 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.

A total of 10 patients received rVWF alone, 12 did not receive any preoperative rFVIII, and 2 did not receive rVWF postoperatively.

The study’s primary endpoint was met. 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.

One patient developed deep vein thrombosis 3 days after undergoing hip replacement surgery; another 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 at the World Federation of Hemophilia World Congress in May 2018.
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The European Commission has granted Shire marketing authorization for vonicog alfa (Veyvondi), a recombinant von Willebrand factor (rVWF) product.

The European Commission (EC) approved vonicog alfa for the treatment of bleeding events and treatment/prevention of surgical bleeding in adults with von Willebrand disease (VWD) when desmopressin treatment alone is ineffective or not indicated.

The product was approved in the United States in 2015 for on-demand treatment and control of bleeding episodes in adults.

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 nonsurgical setting.

Data from these studies are available in the Summary of Product Characteristics for vonicog alfa.The phase 1 trial (NCT00816660) enrolled patients with type 3 or severe type 1 VWD.

The goal was to assess the safety and pharmacokinetics of vonicog alfa combined at a fixed ratio with recombinant factor VIII – referred to as “rVWF-rFVIII.” The researchers compared rVWF-rFVIII with 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. These results were published in Blood (2013 Aug 1;122[5]:648-57).The phase 3 nonsurgical study (NCT01410227) included 49 patients with VWD who received vonicog alfa with or without rFVIII.

All participants had successful treatment of bleeding episodes. Nearly all (96.9%) treated bleeds were given an “excellent” efficacy rating and most (81.8%) were resolved with a single infusion of vonicog alfa; the treatment had a mean half-life of 21.9 hours.

There were eight adverse events considered related to vonicog alfa, two of which were serious. There were no thrombotic events, no treatment-related binding or neutralizing antibodies against VWF, and no neutralizing antibodies against FVIII. These results were published in Blood (2015 Oct 22;126[17]:2038-46).

The phase 3 surgical trial (NCT02283268) enrolled 15 adults with severe VWD who were undergoing elective surgical procedures.
 

 

Patients received vonicog alfa at 40-60 IU per kg of body weight 12-24 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.

A total of 10 patients received rVWF alone, 12 did not receive any preoperative rFVIII, and 2 did not receive rVWF postoperatively.

The study’s primary endpoint was met. 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.

One patient developed deep vein thrombosis 3 days after undergoing hip replacement surgery; another 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 at the World Federation of Hemophilia World Congress in May 2018.

 

The European Commission has granted Shire marketing authorization for vonicog alfa (Veyvondi), a recombinant von Willebrand factor (rVWF) product.

The European Commission (EC) approved vonicog alfa for the treatment of bleeding events and treatment/prevention of surgical bleeding in adults with von Willebrand disease (VWD) when desmopressin treatment alone is ineffective or not indicated.

The product was approved in the United States in 2015 for on-demand treatment and control of bleeding episodes in adults.

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 nonsurgical setting.

Data from these studies are available in the Summary of Product Characteristics for vonicog alfa.The phase 1 trial (NCT00816660) enrolled patients with type 3 or severe type 1 VWD.

The goal was to assess the safety and pharmacokinetics of vonicog alfa combined at a fixed ratio with recombinant factor VIII – referred to as “rVWF-rFVIII.” The researchers compared rVWF-rFVIII with 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. These results were published in Blood (2013 Aug 1;122[5]:648-57).The phase 3 nonsurgical study (NCT01410227) included 49 patients with VWD who received vonicog alfa with or without rFVIII.

All participants had successful treatment of bleeding episodes. Nearly all (96.9%) treated bleeds were given an “excellent” efficacy rating and most (81.8%) were resolved with a single infusion of vonicog alfa; the treatment had a mean half-life of 21.9 hours.

There were eight adverse events considered related to vonicog alfa, two of which were serious. There were no thrombotic events, no treatment-related binding or neutralizing antibodies against VWF, and no neutralizing antibodies against FVIII. These results were published in Blood (2015 Oct 22;126[17]:2038-46).

The phase 3 surgical trial (NCT02283268) enrolled 15 adults with severe VWD who were undergoing elective surgical procedures.
 

 

Patients received vonicog alfa at 40-60 IU per kg of body weight 12-24 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.

A total of 10 patients received rVWF alone, 12 did not receive any preoperative rFVIII, and 2 did not receive rVWF postoperatively.

The study’s primary endpoint was met. 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.

One patient developed deep vein thrombosis 3 days after undergoing hip replacement surgery; another 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 at the World Federation of Hemophilia World Congress in May 2018.
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