Our PatientsOur PeopleOur BusinessOur Community © 2008 Endo Pharmaceuticals. All Rights Reserved. Biosimilars 2009 Update Pending Legislation Review Pam Politis AIPLA Spring Meeting 2009 May 14, 2009

2 Follow-on Biologics Bills in the House of Representatives 2009 H.R Waxman Bill Promoting Innovation and Access to Life-Saving Medicine Act Introduced March 11, 2009 Amendment to Public Health Services Act 42 U.S.C. § 262 Supported by GPhA, AARP, Labor Unions, Managed Care Groups H.R Eshoo Bill Pathway for Biosimilars Act Introduced March 17, 2009 Amendment to Public Health Services Act 42 U.S.C. § 262 Supported by PhRMA, BIO

3 Follow-on Biologics Bills-Similarities Permit follow-on applicant to reference Approved Product Data Two Possible Designations with Approval: Biosimilar and Interchangeable Application Data –Biosimilar Analytical Studies-chemical, physical, biological Animal studies Necessary clinical studies to demonstrate safety, purity, and potency* *Eshoo Bill requires trials for the purpose of assessing immunogenicity.

4 Follow-on Biologics Bills-Similarities H.R Waxman Bill Biosimilar: “no clinically meaningful differences between the biological product and the reference product would be expected in terms of the safety, purity, and potency if treatment were to be initiated with the biological product instead of the reference product.” H.R Eshoo Bill Biosimilar: “highly similar” to reference product. DEFINITION OF BIOSIMILAR

5 Follow-on Biologics Bills-INTERCHANGEABLE H.R Waxman Bill Interchangeable Biological Product: –Biosimilar to reference product; –Can safely “switch” patients H.R Eshoo Bill Interchangeable Biological Product: –Biosimilar to reference product and all other interchangeable products; –All approved uses of the reference product; –Can safely “switch” patients –Final guidance on interchangeability of the product class.

6 Follow-on Biologics Bills-Market Exclusivity 5 years –extendable by 6 months 3 years for Similar Substance Exclusivity Adjustment –6 month extension limited for products with annual gross U.S. sales of over $1 billion. 12 years –Extendable by 2 years if extension is requested during first 8 years after approval At least 4 years DATA exclusivity –FDA must have initiated guidance proceedings H.R Waxman BillH.R Eshoo Bill FDA WILL NOT APPROVE FOB APPLICATION

7 Reference Product Holder Burden to Disclose Notice is Discretionary! FOB Applicant asks for Patent information from RP sponsor –RP Sponsor MUST identify all “related patents” –Must update for 2 years Anytime after FOB application is filed, FOB may send notice.* Disclosure Burden on FOB Applicant FOB sends application to RP sponsor w/in 30 days RP sponsor sends list of patents (60 days) FOB certifies (30 days) 3 rd Party Patents Too!!! Follow-on Biologics Bills-Patent Notices H.R Waxman BillH.R Eshoo Bill NO ORANGE BOOK!

8 Within 45 days of receiving notice, RP Holder may file suit –Only for patents in notice, i.e. those patents the FOB applicant selected. If no suit on notice patents FOB applicant may bring DJ action If no suit in 45 day period, any later suit limited to reasonable royalities. Not Listed = No Suit! Trial court decision of infringement prevents FDA approval until patent expires. No possibility of “at risk” launch for RP who wins trial court decision. FOB cannot bring DJ action until 3 years prior to market exclusivity expiration. Third Parties Too! Follow-on Biologics Bills-Patent Suits H.R Waxman BillH.R Eshoo Bill NO 30 MONTH STAY!

9 FOB can pick one indication for approval –Reduces clinical trial burden without market consequence. Guidance Document to be issued, but not required for approval. Biosimilar has same official name as reference product NO Auth. Biosimilars during exclusivity period. Biosimilarity and Interchangeability must be demonstrated for every use in the reference product label. Guidance Documents Required for Each Product Class!! Every biological product has unique official name. Follow-on Biologics Bills- DIFFERENCES H.R Waxman BillH.R Eshoo Bill BIAS IN THE DETAILS!

10 Canada-Subsequent Entry Biologics Detailed Guidance Issued March 27,2009 –Detailed expectations for data comparisons between SEB and reference product. –Importance of manufacturing and Quality data stressed Allows for “Biosimilar” designation, not interchangeable. –SEB must create independent label, setting forth data supporting similarity to reference product. –No claims for bioequivalence or therapeutic equivalence may be made In the label. Provides 6 years data exclusivity Patent Notice and litigation provisions identical to generic drug pathway (same as Hatch-Waxman) First SEB (Omnitrope™) approved April 22, 2009