Formulary Review: Prasugrel (Effient ®) Safety and Efficacy of a New Acute Coronary Syndrome Drug

1. Pitt Street Health Plan Striving for Excellence in Managed Care Formulary Review: Prasugrel (Effient ®)Safety and Efficacy of a New Acute Coronary Syndrome Drug • Pharmaceutics and Therapeutics Committee • Spring, 2011 • Abby Stoddard • Sarah Shore • Justine Meierhofer • Caitlin Wilke

2. Objectives • Determine formulary status for Eli Lilly’s drug: Prasugrel • Provide systematic review: • Drug Properties • Clinical Analysis • Financial Considerations • Offer recommendation Pitt Street Health Plan Striving for Excellence in Managed Care

3. Pitt Street Health Mission “Pitt Street Health Plan provides integrated, comprehensive, and high quality healthcare coverage. We carry a commitment to excellence, and are bound to employ cost-effective methods to provide the finest service and prices for our beneficiaries.” Pitt Street Health Plan Striving for Excellence in Managed Care

4. Formulary Decision-Making Recommendation

5. Drug Properties - FDA Indications/Cautions

6. Drug Properties – Drug Effects

7. Drug Properties – Metabolism Both prasugrel and clopidogrel are prodrugs Genetic basis non-responders up to XX% in prasugrel Prasugrel is favorable over clopidogrel via less genetic variation in response and CYP enzyme-mediated drug interactions Non-responders up to XX% in clopidogrel No known clinically significant prasugrel drug interactions on basis of CYP metabolism Clopidogrel interacts significantly with other CYP2C19 drugs

8. Drug Properties– Interactions/Kinetics

9. Drug Properties – Drug Effects

10. Clinical Analysis TRITON-TIMI 38 POST-HOC ANALYSIS JUMBO-TIMI 26 Key Trials Evaluating Prasugrel Efficacy and Safety ACAPULCO PRINCIPLE-TIMI 41

11. Clinical Analysis

12. Clinical Analysis - Efficacy

13. Clinical Analysis - Efficacy

14. Clinical Analysis - Efficacy Clopidogrel Clopidogrel Prasugrel Prasugrel

15. Clinical Analysis - Safety

16. Clinical Analysis - Safety TIMI (Major/Minor) Fatal Life-Threatening Non-CABG TIMI (Major)

17. Clinical Analysis - Safety Non-CABG TIMI Major/Minor/Minimal Clopidogrel Non-CABG TIMI Major Prasugrel Non-CABG TIMI Major/Minor

18. Clinical Analysis – Post-HOC Analysis

19. Financial Considerations 2,650,000 Covered Lives 4,121 Pitt Street patients eligible for prasugrel Savings of $221 per prasugrel recipient over 40 years Formulary prasugrel could save Pitt Street Health $797,615 annually over formulary clopidogrel alone* $283 paid by Pitt Street for each life- year gained QaLY added pras. v. clop.= 0.097 (CI 0.043-0.148) *See handout for calculation details

20. Financial Considerations– Sub-Group Analysis PCI without DES Male STEMI Non-STEMI Female PCI with DES

21. Financial Considerations– Value Preposition Total Costs Cost of Re-hospitalization Index Hospitalization

22. Financial Considerations- Therapy Crossover • Other benefit manager’s formulary status of prasugrel may influence prescribing patterns • Pitt Street Health utilization management program risks therapy discontinuation or interruption • TRITON-TIMI STEMI patients exhibited greatest CV protection benefit at 18 days after therapy initiation

23. Financial Considerations- Upcoming Market Changes

24. Financial Considerations- Pitt Street Health Beneficiaries Eligible for Prasugrel Annually: 4,121

25. Recommendation

26. Recommendation

27. Pitt Street Health Mission “Pitt Street Health Plan provides integrated, comprehensive, and high quality healthcare coverage. We carry a commitment to excellence, and are bound to employ cost-effective methods to provide the finest service and prices for our beneficiaries.” Pitt Street Health Plan Striving for Excellence in Managed Care

28. Recommendation Add Prasugrel to Pitt Street Health Formulary Pitt Street Health Plan Striving for Excellence in Managed Care

29. Works Cited References: Blue Cross and Blue Shield of MN. Retrieved January 18, 2011. http://www.bluecrossmn.com/bc/wcs/groups/bcbsmn/@mbc_bluecrossmn/documents/public/mbc1_home_index.hcsp. Effient package insert. Daiichi Sankyo Inc. and Eli Lilly and Co. Indianapolis, IN. 2009 July. Empire Blue Cross and Blue Shield of NY. Retrieved January 18, 2011. http://www.individual-health-plans.com/empire.htm. Eugene Braunwald, Elliott M. Antman, John W. Beasley, Robert M. Califf, Melvin D. Cheitlin, Judith S. Hochman, Robert H. Jones, Dean Kereiakes, Joel Kupersmith, Thomas N. Levin, Carl J. Pepine, John W. Schaeffer, Earl E. Smith, III, David E. Steward, Pierre Theroux, Raymond J. Gibbons, Joseph S. Alpert, Kim A. Eagle, David P. Faxon, Valentin Fuster, Timothy J. Gardner, Gabriel Gregoratos, Richard O. Russell, and Sidney C. Smith, Jr. ACC/AHA Guidelines for the Management of Patients With Unstable Angina and Non–ST-Segment Elevation Myocardial Infarction: Executive Summary and Recommendations : A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Unstable Angina) Circulation, Sep 2000; 102: 1193 - 1209.  HealthPartners. Retrieved January 18, 2011. http://www.heatlhpartners.com/public/. Mackenzie, I S, Coughtrie, M W H, MacDonald, T M, et al. (2010). Antiplatelet drug interactions. Journal of internal medicine, 268(6), 516-529. Medica Health Plans. Retrieved January 18, 2011. http://www.medica.com. Montalescot G, Sideris G, Cohen R, Meuleman C, Bal dit Sollier C, Barthelemy O, Henry P, Lim P, Beygui F, Collet JP, Marshall D, Luo J, Petitjean H, Drouet L. Prasugrel Compared with High-Dose Clopidogrel in Acute Coronary Syndrome: The randomized, double-blind ACAPULCO Study. Thromb Haemost. 2010; 103: 213-223.

30. Works Cited References: National Center for Health Statistics. Health, United States, 2009: With Special Feature on Medical Technology. Hyattsville, MD. 2010. Plavix package insert. Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership. Bridgewater, NJ. 2010 August. Prasugrel. Retrieved January 7, 2011 from Micromedex. Rehmel, J L, Eckstein, J A, Farid, N A, et al. (2006). Interactions of two major metabolites of prasugrel, a thienopyridine antiplatelet agent, with the cytochromes p450. Drug metabolism and disposition, 34(4), 600-607. Testa, L, Biondi Zoccai, G G, Valgimigli, M, et al. (2010). Current concepts on antiplatelet therapy: Focus on the novel thienopyridine and non-thienopyridine agents. Advances in Hematology, 2010, 595934-595934. Veteran's Affairs Pharmacy Benefit Management Services, Medical Advisory Panel and VISN Pharmacist Executives (2010). National PBM Monograph Template Rev20091005 - Prasugrel. United States Department of Veterans Affairs. Retrieved January 18, 2011. www.pbm.va.gov/Clinical%20Guidance/Drug%20Monographs/Prasugrel%20Monog. Wiviott SD, Antman EM, Winters KJ, Weerakkody G, Murphy SA, Behounek BD, Carney RJ, Lazzam C, McKay RG, McCabe CH, Braunwald E. Randomized Comparison of Prasugrel (CS-747, LY640315), a Novel Thienopyridine P2Y12 Antagonist, With Clopidogrel in Percutaneous Coronary Intervention: Results of the Joint Utilization of Medications to Block Platelets Optimally (JUMBO)- TIMI 26 Trial. Circulation. 2005; 111: 3366-3373. Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S, Neumann FJ, Ardissino D, De Servi S, Murphy SA, Riesmeyer J, Weerakkody G, Gibson CM, Antman EM. Prasugrel Versus Clopidogrel in Patients with Acute Coronary Syndromes. N Engl J Med. 2007; 357: 2001-2015. Wiviott SD, Trenk D, Frelinger AL, O’Donoghue M, Neuman FJ, Michelson A, Angiolillo DJ, Hod H, Montalescot G, Miller DL, Jakubowski JA, Cairns R, Murphy SA, McCabe CH, Antman EM, Braunwald E. Prasugrel Compared with High Loading- and Maintenance-Dose Clopidogrel in Patients with Planned Percutaneous Coronary Intervention: The Prasugrel in Comparison to Clopidogrel for Inhibition of Platelet Activation and Aggregation- Thrombolysis in Myocardial Infarction 44 Trial. Circulation. 2007; 116:2923-2932.