INTERCEPT Blood System for Platelets
Safety and Efficacy Data: Clinical Use

Buffy Coat Platelets
A randomized, controlled, double-blinded clinical trial was performed to evaluate the efficacy and safety of platelets prepared by the buffy coat method treated with the INTERCEPT Blood System. The results of this 103 patient clinical trial demonstrated that INTERCEPT buffy coat platelets can be used in the same manner as untreated platelets for the support of thrombocytopenic patients. Equal doses of INTERCEPT buffy coat platelets provided similar one and 24-hour post-transfusion count increments, and patients treated with INTERCEPT buffy coat platelets exhibited adverse event profiles similar to those who received reference platelets.

Apheresis Platelets
A randomized, controlled, double-blinded clinical trial was performed to evaluate the efficacy and safety of apheresis platelets collected on the Amicus Cell Separator and treated with the INTERCEPT Blood System. The results of this 43 patient clinical trial confirmed the results of the larger trial performed with buffy coat platelets.

A second randomized, controlled, double-blinded clinical trial was performed evaluating the hemostatic efficacy and safety of transfusion of apheresis platelet concentrates collected on the Amicus Cell Separator treated with the INTERCEPT Blood System in thrombocytopenic patients (n=645). The results from this large trial demonstrated equivalence of INTERCEPT apheresis platelets to conventional apheresis platelets in prevention and treatment of Grade 2 and higher grade bleeding, according to WHO criteria (McCullough, Vesole et al. 2004). An increase in 3 specific pulmonary events: acute respiratory distress syndrome, pneumonitis not otherwise specified (nos), and pleuritic chest pain was noted in the INTERCEPT group. Subsequent analyses and expert consultation indicated that the observed differences in these adverse events were related to inconsistencies of verbatim terms used for MedDRA coding dictionary and inconsistent reporting of events of acute respiratory distress syndrome by study personnel, and that there were no differences between the INTERCEPT platelets and conventional platelets with respect to serious pulmonary events.

7-Day Platelets
A randomized, double-blind, single-center, two-treatment, two-period cross-over clinical study was conducted to determine whether buffy coat platelets treated with the INTERCEPT Blood System and stored for 7 days provided safety and acceptable therapeutic efficacy when compared to 7-day old Reference platelet concentrates in the treatment of thrombocytopenic patients.

Transfusion of INTERCEPT Platelets stored for 7 days resulted in acceptable clinical outcomes; although, non-inferiority to 7-day old Reference platelets in terms of 1-hour CCI could not be demonstrated with the pre-specified non-inferiority margin of 2.2x10³.

The results of the study demonstrated that both INTERCEPT and Reference Platelets stored for 7 days were capable of preventing bleeding. Platelet transfusions with 7-day old platelets prepared with the INTERCEPT Blood System were shown to be safe and well-tolerated in thrombocytopenic patients and had a similar profile to transfusions with conventionally produced 7-day old platelets.

Post-Marketing Experience
Following CE Mark approval, a hemovigilance (HV) program to document and characterize the safety profile of INTERCEPT Platelets in routine use was initiated. The objective of the observational, non-randomized, non-controlled hemovigilance program was to gain additional safety experience with INTERCEPT Platelets as they are prepared and transfused under routine blood bank and clinical conditions, respectively, and to gain additional experience in broad patient populations. To date more than 100,000 transfusions of INTERCEPT Platelets have been administered to thrombocytopenic patients in routine clinical use. Of that, safety data on 12,543 transfusions have been collected in two HV studies completed to date (5,106 transfusions (HV1) and 7,437 transfusions (HV2)). These non-interventional studies have been performed at multiple sites in Europe. INTERCEPT treatment was used in place of gamma irradiation for prevention of TA-GVHD in most of these centers. Related adverse events following INTERCEPT platelet transfusions were infrequent and most were of mild severity (grade 1). The most frequently reported signs/symptoms were fever, chills, urticaria and other dermatological reactions. These types of reactions have previously been described in association with platelet transfusions. No unexpected adverse events were observed during the conduct of these studies. In HV1, there were 3 adverse events grade 2 or higher (one of which was possibly related). In HV2, there were 5 adverse events grade 2 or higher (all of which were unrelated or probably unrelated). No reports of TA-GVHD events related to the transfusion were noted in either study. This is especially important since >95% of platelet components were not gamma irradiated and many were given to at-risk immune compromised patients.

Technical Data Sheets section page 7 of 7