Joint Dermatologic and Ophthalmic Drugs & Drug Safety and Risk Management Advisory Committee February 26 & 27, 2004 S ystem for T halidomide E ducation and P rescribing S afety™ Selected Topics of Interest Thalomid® (thalidomide) NDA Celgene, Corp.

Joint Dermatologic and Ophthalmic Drugs & Drug Safety and Risk Management Advisory Committee February 26 & 27, S.T.E.P.S. Program Objectives To prevent fetal exposures to thalidomide To educate regarding risks of thalidomide To provide procedures to reduce risk of fetal exposure to thalidomide To identify at-risk behaviors by surveying patients and prescribers To provide a mechanism for intervention & remediation when at-risk behaviors identified via S.T.E.P.S. Serves as the mechanism for restricted distribution To prevent fetal exposures to thalidomide To educate regarding risks of thalidomide To provide procedures to reduce risk of fetal exposure to thalidomide To identify at-risk behaviors by surveying patients and prescribers To provide a mechanism for intervention & remediation when at-risk behaviors identified via S.T.E.P.S. Serves as the mechanism for restricted distribution

Joint Dermatologic and Ophthalmic Drugs & Drug Safety and Risk Management Advisory Committee February 26 & 27, OLD S.T.E.P.S. Physician Visit Consent Signed Drug Dispensed to patient 1 3 BU Prescription Provided, Pharmacist to dispense Survey Provided Action After therapy initiation 2

Joint Dermatologic and Ophthalmic Drugs & Drug Safety and Risk Management Advisory Committee February 26 & 27, “Old” STEPS - Areas for Improvement At-risk behaviors from BU survey identified only after drug dispensed –Time delay to identification of at-risk behavior and intervention is suboptimal –BUSEC’s primary focus is not real-time patient interventions Program design could do more to assure compliance with program procedures (e.g. HCG tests) Program has limited risk groups categories (M/F) doesn’t allow for targeted risk management strategies (e.g. AFCBP vs. AFNCBP) Program doesn’t utilize current technologies –Target specific risk groups –Record availability/storage/management/archiving –Efficiency/quality of accounting/auditing/reporting on STEPS activities At-risk behaviors from BU survey identified only after drug dispensed –Time delay to identification of at-risk behavior and intervention is suboptimal –BUSEC’s primary focus is not real-time patient interventions Program design could do more to assure compliance with program procedures (e.g. HCG tests) Program has limited risk groups categories (M/F) doesn’t allow for targeted risk management strategies (e.g. AFCBP vs. AFNCBP) Program doesn’t utilize current technologies –Target specific risk groups –Record availability/storage/management/archiving –Efficiency/quality of accounting/auditing/reporting on STEPS activities

Joint Dermatologic and Ophthalmic Drugs & Drug Safety and Risk Management Advisory Committee February 26 & 27, “New” S.T.E.P.S.™ - 1 Launched July 30, 2001 Address areas for improvement identified in “Old” STEPS Many of the elements the same –Registration of Prescriber, Pharmacist, and Patient –Educational materials brochure & video tape –Patient counseling / education –Limit to 28-day supply of Thalomid (blister packs) –Call healthcare provider for any suspected fetal exposure (M or F) number for Celgene provided –No blood donation –Contraception (FCBP) & latex condoms (males) –Pregnancy tests unchanged Launched July 30, 2001 Address areas for improvement identified in “Old” STEPS Many of the elements the same –Registration of Prescriber, Pharmacist, and Patient –Educational materials brochure & video tape –Patient counseling / education –Limit to 28-day supply of Thalomid (blister packs) –Call healthcare provider for any suspected fetal exposure (M or F) number for Celgene provided –No blood donation –Contraception (FCBP) & latex condoms (males) –Pregnancy tests unchanged

Joint Dermatologic and Ophthalmic Drugs & Drug Safety and Risk Management Advisory Committee February 26 & 27, “New” S.T.E.P.S.™ - 2 Six Risk Groups –Adult females of childbearing potential –Adult females not of childbearing potential –Female children of childbearing potential –Female children not of childbearing potential –Adult males –Male children Consent forms computer generated for specific risk group based upon responses entered into program - includes (DOB, address, diagnosis for Thalomid treatment) Must participate in Registry and telephonic interactive voice response system (IVR) survey (Celgene administers and performs interventions) BUSEC Follow-up Survey now optional - utilizes risk groups (n=6) –Quality assurance / program evaluation Six Risk Groups –Adult females of childbearing potential –Adult females not of childbearing potential –Female children of childbearing potential –Female children not of childbearing potential –Adult males –Male children Consent forms computer generated for specific risk group based upon responses entered into program - includes (DOB, address, diagnosis for Thalomid treatment) Must participate in Registry and telephonic interactive voice response system (IVR) survey (Celgene administers and performs interventions) BUSEC Follow-up Survey now optional - utilizes risk groups (n=6) –Quality assurance / program evaluation

Joint Dermatologic and Ophthalmic Drugs & Drug Safety and Risk Management Advisory Committee February 26 & 27, IVRIVR IVR = Interactive Voice Response System a brief, automated, telephone-based survey (Celgene administers) survey questions are tailored to patient’s specific risk group a tool designed to –identify at-risk behavior and trigger real-time interventions (Celgene intervenes) –foster compliance with STEPS program procedures The IVR system is used to “activate” prescriptions IVR = Interactive Voice Response System a brief, automated, telephone-based survey (Celgene administers) survey questions are tailored to patient’s specific risk group a tool designed to –identify at-risk behavior and trigger real-time interventions (Celgene intervenes) –foster compliance with STEPS program procedures The IVR system is used to “activate” prescriptions

Joint Dermatologic and Ophthalmic Drugs & Drug Safety and Risk Management Advisory Committee February 26 & 27, NEW S.T.E.P.S. Physician Visit Consent Signed Celgene Voice Response System Drug Dispensed to patient Blinded Patient List Sent to BU (ALL patients) not implemented yet, etc A B BU Prescription Provided, Pharmacist to dispense Physician calls IVR Patient calls IVR Pharmacist calls IVR Envelope supplied to mail back to BU should the patient agree to participate Celgene mails initial survey with unique identifier not implemented yet

Joint Dermatologic and Ophthalmic Drugs & Drug Safety and Risk Management Advisory Committee February 26 & 27, S.T.E.P.S. Overview Approximately 65,000 patients registered since July, rd Quarter, 2003: –Approximately 50,000 surveys completed (mandatory compliance survey conducted by Celgene) –Approximately 5% were “flagged” and required an intervention prior to prescription activation –The largest proportion of “flagged surveys” was in the FCBP risk group, mostly related to outdated pregnancy tests Approximately 65,000 patients registered since July, rd Quarter, 2003: –Approximately 50,000 surveys completed (mandatory compliance survey conducted by Celgene) –Approximately 5% were “flagged” and required an intervention prior to prescription activation –The largest proportion of “flagged surveys” was in the FCBP risk group, mostly related to outdated pregnancy tests

Joint Dermatologic and Ophthalmic Drugs & Drug Safety and Risk Management Advisory Committee February 26 & 27, Percentage of women experiencing unintended pregnancy during 1 st year (perfect use) Periodic abstinence1-9 Male condom3 Diaphragm6 Oral contraceptives0.1 Injectable methods0.3 IUD Surgical –Vasectomy0.1 –Tubal ligation0.5 Periodic abstinence1-9 Male condom3 Diaphragm6 Oral contraceptives0.1 Injectable methods0.3 IUD Surgical –Vasectomy0.1 –Tubal ligation0.5 Source: Contraceptive Technology, 1998

Joint Dermatologic and Ophthalmic Drugs & Drug Safety and Risk Management Advisory Committee February 26 & 27, Contraception Failure (rates per 1,000) Periodic abstinence198 Male condom90 Diaphragm81 Oral contraceptives70 Injectable methods32 IUD5-14* Surgical –Vasectomy<10 –Tubal ligation * Cumulative 5-year failure rates Periodic abstinence198 Male condom90 Diaphragm81 Oral contraceptives70 Injectable methods32 IUD5-14* Surgical –Vasectomy<10 –Tubal ligation * Cumulative 5-year failure rates Source: ACOG Bulletin No. 46, Sept 2003