1. Accutane FDA (Section Name - Saver’s Initials) 3/9/00 12:50 PM 1 Introduction Russell Ellison, MD Chief Medical Officer Vice President, Medical Affairs Roche Laboratories, Inc.

2. “..... Accutane is uniquely and highly effective for the most severe form of acne, which if not adequately treated causes significant and often permanent disfigurement.” “..... Accutane is uniquely and highly effective for the most severe form of acne, which if not adequately treated causes significant and often permanent disfigurement.”

3. Accutane is a potent teratogen

4. Accutane History Introduced in the US in 1982 for Severe Recalcitrant Nodular Acne Introduced in the US in 1982 for Severe Recalcitrant Nodular Acne 5 million patients in the US; 12 million worldwide 5 million patients in the US; 12 million worldwide Use has been increasing since 1991 Use has been increasing since 1991

5. Accutane and Pregnancy Roche introduced the Pregnancy Prevention Program in 1988, modified in 1989, to prevent fetal exposure by the prevention of pregnancy Roche introduced the Pregnancy Prevention Program in 1988, modified in 1989, to prevent fetal exposure by the prevention of pregnancy –the pregnancy rate is declining –the pregnancy rate in women on Accutane is about 80-90% less than for those with normal contraceptive use –for every 1000 women treated with Accutane, pregnancy has not occurred in 997

6. Accutane and Pregnancy The Accutane survey [Slone Epidemiology Unit] was introduced in 1989 as part of the Pregnancy Prevention Program The Accutane survey [Slone Epidemiology Unit] was introduced in 1989 as part of the Pregnancy Prevention Program –500,000 enrollees –yearly enrollment doubled since 1989 –available evidence supports that the survey enrollees are representative of the Accutane treated population

7. HOWEVER: While an individual’s risk of pregnancy is decreasing, the total public health burden has not. While an individual’s risk of pregnancy is decreasing, the total public health burden has not. ie: the absolute number of exposed pregnancies has not decreased ie: the absolute number of exposed pregnancies has not decreased

8. The absolute goal is the prevention of pregnancy

9. Roche’s Goal Roche is committed to the optimal program to further prevent pregnancies balancing Roche is committed to the optimal program to further prevent pregnancies balancing –likelihood of success –risk of compromising current success –risk of denying treatment to patients who would not become pregnant

10. Targeted Pregnancy Prevention Program A Targeted Pregnancy Prevention Program, specifically addressing the behaviors leading to pregnancies in women on Accutane, was introduced this year A Targeted Pregnancy Prevention Program, specifically addressing the behaviors leading to pregnancies in women on Accutane, was introduced this year

11. Agenda Introduction Russell Ellison, MD Introduction Russell Ellison, MD Chief Medical Officer, Vice President/Medical Affairs Roche Laboratories, Inc. Benefits Guy Webster, MD Benefits Guy Webster, MD Vice Chairman/Department of Dermatology Jefferson Medical College.

12. Agenda Risk Detection: Risk Detection:Epidemiology John La Flore, MD, MSPH Vice President/ Drug Safety & Risk Management Roche Laboratories, Inc. Risk Assessment: Risk Assessment: Accutane Survey Allen Mitchell, MD Director/Slone Epidemiology Unit Boston University School of Public Health

13. Agenda Risk Management & Intervention: Targeted Pregnancy Prevention Program Risk Management & Intervention: Targeted Pregnancy Prevention Program Eileen Leach, RN, MPH Medical Director/Dermatology/Marketing Roche Laboratories, Inc. Other Risk Management Options: Other Risk Management Options: Russell Ellison, MD Chief Medical Officer, Vice President/Medical Affairs Roche Laboratories, Inc