Summary Safety Review - KOGENATE FS/HELIXATE FS - Assessing the Potential Changes in the Known Risk of Inhibitors (Inhibitory Antibody - IA) Development in Previously Untreated Patients with Severe Hemophilia A

July 26, 2016


Kogenate FS/Helixate FS (Antihemophilic Factor [Recombinant])

Potential Safety Issue

Potential changes in the known risk of the development of inhibitors (inhibitory antibodies) in previously untreated patients (PUPs) with severe hemophilia A

Key Messages

  • Kogenate FS and Helixate FS are used for the treatment of classical hemophilia A, a disease that prevents the blood from clotting properly.
  • Health Canada carried out a safety review based on recent published studies that suggested an increased risk of developing inhibitors (inhibitory antibodies) to Kogenate FS/Helixate FS compared to similar medicines. The result is that the treatment may fail to prevent or stop episodes of bleeding.
  • Health Canada’s safety review concluded that the recent evidence does not present a new safety concern and the Kogenate FS/Helixate FS product information already warns of this potential event. Health Canada will continue to monitor the issue of IA development when these products are used.


Inhibitor antibodies (IA) development is a known concern in hemophilia A patients treated with antihemophilic factors. IA are a result of the immune system reacting to the treatment. IA development may cause the treatment to fail to prevent or stop a bleeding episode. This is especially concerning in young children with severe hemophilia A during their first years of treatment and any patient who has had limited previous treatment with factor VIII products (also known as ‘previously untreated patients’ or ‘PUPs’). Some published studies suggested that Kogenate FS/Helixate FS may be linked to a greater risk of development of IA in PUPs compared to similar factor VIII products. The safety review by Health Canada was carried out to determine if the risk of inhibitor development was greater with Kogenate FS/Helixate FS use in PUPs compared to similar medicines and whether more actions were needed to manage this risk.

Use in Canada

  • Kogenate FS and Helixate FS are identical blood clotting factor VIII products. They are very similar to the factor VIII that is made naturally in human blood. These products have been marketed in Canada since 2000 and 2008, respectively.
  • They are both used for the treatment of adults and children with classical hemophilia A as a replacement for the missing clotting factor. In these patients, the products help to prevent bleeding episodes or stop a bleeding episode that has already begun. They can manage bleeding during emergency or scheduled surgery and can also help prevent joint damage in children.

Safety Review Findings

  • Health Canada had received reports related to IA development associated with the use of Kogenate FS/Helixate FS, or instances where these products were not working. The reports represented 31 Canadian patientsFootnote a with hemophilia and included both children and adults. Overall, these Canadian reports did not provide enough information to conclude that there is a greater risk of IA development when Kogenate FS/Helixate FS is used in PUPs as compared to similar products.
  • The review also looked into recent published studiesFootnote 1 Footnote 2 Footnote 3  of hemophilia A patients treated with factor VIII products. While the studies suggested there is a potential increased risk of IA development in PUPs treated with Kogenate FS/Helixate FS, there were concerns with how the studies were designed and analyzed. As a result, this information could not show that the use of Kogenate FS/Helixate FS carries a greater risk of the development of IA in PUPs with severe hemophilia A as compared to similar products.

Conclusions and Actions

  • Health Canada’s safety review concluded that the evidence does not suggest any additional concerns regarding the risk of inhibitors (IA) development toward Kogenate FS/Helixate FS, and the Canadian labels for these products have warnings regarding the risk of inhibitor development.
  • Health Canada has requested that the manufacturers continue to share any new information related to this risk, as it becomes available.
  • Health Canada will continue to monitor safety information involving Kogenate FS/Helixate FS, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action if and when any new health risks are identified.

Additional Information

The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this product both in Canada and internationally.


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