A Canadian Prospective, Observational, Open-Label, Pharmacovigilance Study to Assess the Safety of Humate-P^® Injection Volume Reduced (ivr) in Patients with Von Willebrand Disease.

Humate-P^® is a plasma-derived factor VIII / von Willebrand factor concentrate. It is used for the treatment of hemophilia A and acquired factor VIII deficiency and various types of von Willebrand disease (vWD) in more than 30 countries worldwide. Humate-P^® was first approved in Canada in December 2004. It is usually tolerated without reaction. In 2008, CSL Behring introduced Humate-P^® ivr into Canada to replace Humate-P^®. Humate-P^® ivr is identical to Humate-P^® except that it is reconstituted using a lower volume of diluent (Humate-P^® injection volume reduced or ivr). The new lower volume preparation is identical to the currently available licensed preparation in every respect, with the exception that the diluent volume, and therefore the reconstituted volume, is 50% that of the older preparation. To ensure that the new ivr preparation was safe and well tolerated, CSL Behring Canada conducted a pharmacovigilance study designed to assess the safety and tolerability of Humate-P^® ivr in patients with vWD previously treated with Humate-P^®.

Patients of any age with vWD who were previously treated with Humate-P^® were enrolled in the study. Enrolled patients were treated with Humate-P^® ivr according to the approved product labeling upon the recommendation of the investigator and were followed per standard of care. Patient demographic and medical history data were captured by chart review, and adverse event data and other clinical data relating to the administration of Humate-P^® ivr were captured prospectively (in some cases prospective data capture was not feasible for logistical or other reasons, and the data was captured retrospectively). The efficacy of Humate-P^® ivr in achieving hemostasis was evaluated by the investigator according to the following criteria: hemostasis clinically not different from normal (excellent), mildly abnormal hemostasis partial or delayed control of spontaneous bleeding or slight transient oozing from surgical wounds (good), moderately abnormal hemostasis bleeding not fully controlled but no need for additional therapy (moderate); and no improvement at all with continuation of bleeding and need for additional or alternative therapies (poor).

A total of 21 patients (n=21) from 4 centres in Canada were enrolled and completed the study. The study population included 12 male and 9 female patients between the ages of 2 and 83. Ten patients had received Humate-P^® within 1 year prior to their first Humate-P^® ivr infusion. All 21 patients enrolled in the study received Humate-P^® ivr per standard of care for surgery and or bleeding requiring intervention, as follows by System Organ Class: Injury, poisoning and procedural complications (n=4); Investigations (n=2); Surgical and medical procedures (n=11); and Vascular disorders (n=4; 1 case each of epistaxis, haemoptysis, rectal hemorrhage and soft tissue hemorrhage). Ten patients (47.6%) experienced at least 1 adverse event (AE). There were no individual AEs reported more than once. None of the AEs were considered to be related to Humate-P^® ivr. There were no deaths reported during the study and no patient was discontinued from the study due to an AE. There were 3 serious AEs (SAEs) reported in 2 patients (n=2), including 1 cardiac arrest in a 26 year-old female (cardiac arrest due to methadone overdose). None of the 3 SAEs were considered by the investigator to be related to Humate-P^® ivr. Clinical response to Humate-P^® ivr was consistent with previous experience with Humate-P^® in these patients, with 5 patients having a good response and 15 patients having an excellent response with Humate-P^® ivr compared with 5 patients having a good response and 14 patients having an excellent response with Humate-P^®. The overall clinical response in the treatment of bleeding episodes or surgeries was not available for one patient treated with Humate-P^® ivr and two patients treated with Humate-P^®.

Humate-P^® ivr appears to be well tolerated by patients with vWD who have previously been treated with Humate-P^®, with no evidence of safety issues. There is evidence of positive therapeutic experience with Humate-P^® ivr similar to that observed with Humate-P^®.

Tinmouth:Canadian Blood Services: Consultancy; Novartis: Research Funding; CSL: Research Funding; Bayer: Research Funding; Wyeth: Research Funding. Blanchette:CSL - Behring: Research Funding. Ritchie:CSL Behring: Research Funding, travel costs for meetings. Barnes:CSL Behring: Employment. van den Hoef:CSL Behring: Employment.