FDA FVIII vCJD Risk Assessment: A global perspective 15 December 2006 – FDA TSEAC Meeting – Washington, DC Mark W. Skinner WFH President

It is important to avoid the complacency which characterized previous blood borne epidemics in people with hemophilia, while retaining a sense of proportion to this particular issue, and maintain a constant watch on the balance between safety and supply Structured risk-management processes require a strategy for continuous learning and communication A. Farrugia – vCJD and Hemophilia – Further Guidance on Assessing the Risk of Plasma-Derived Products for Treating Hemophilia – WFH 2004 WFH Guidance on Assessing Product Risk

Follow a precautionary approach when scientific knowledge is incomplete Patients have a right to be consulted and informed –Timely communication with openness and transparency –Clear and comprehensible explanations essential –Appropriate to acknowledge areas of uncertainty Avoid unintended health consequences –e.g.) patient stigmatization, denial of access to care Risk Communication Core Values

> $10,000 USD GNP per capita < $10,000 USD GNP per capita Potential Global Implications Source: WFH Global Survey 2005; Random sample of 45 countries 75% of the patients in the world receive little or no care Outside of the highly developed nations, treatment products are predominantly plasma-derived

Placing Risk in Context Mortality and Causes of Death in PWH Before the introduction of clotting factor preparations, the mean life expectancy of patients with hemophilia was <30 years, and patients mostly died of intracranial or other hemorrhages In patients with severe hemophilia not infected with viruses, mortality is still 40% higher when compared with the general population 27% (13/49) of the deaths in the cohort of patients not infected with HCV or HIV were because of hemorrhage PLUG, I., et. al., Mortality and causes of death in patients with hemophilia, 1992–2001: a prospective cohort study. Journal of Thrombosis and Haemostasis 4 (3), doi: /j x

Quantifying the Risk in Global Context FDA risk assessment builds on global knowledge and understanding –U.K. 2004: U.K. plasma-derived concentrates 1% additional risk beyond general population risk of 1:4,225 to 1.8:1,000,000 –FDA 2006: U.S. plasma-derived concentrates between 1:105,000 & 1:9,400,000 FDA assessment is significantly lower than the U.K. assessment and thus provides further reassurance for patients & clinicians

The FDA assessment adds to our understanding and provides reassurance for both clinicians and patients when making treatment product selection decisions The WFH continues to view both recombinant and plasma-derived products as important treatment options for the global bleeding disorders community Potential remains for adverse events including inhibitor development or unknown pathogen risk, thus continuous learning and communication are required Selection of Treatment Product