Xarelto Fatalities Update 2015

1. XARELTO (rivaroxaban) Update on XARELTO Mass Tort Litigation June 23, 2015

2. Webinar Sponsor

3. gabe@pathtojustice.com

4. Why Anticoagulants? • Blood Thinners make the blood “thinner” and inhibit clotting • Blood clots can block blood vessels leading to strokes or heart attacks • Blood clots can travel to lungs (emboli) or legs (deep vein thrombosis) • Clotting occurs through a complicated process • Post-Surgery blood clots can lead to complications including Deep Vein Thrombosis (DVT) Pulmonary Emboli (PE) from reduced activity during recuperation

5. http://www.heart.org/idc/groups/heart-public/@wcm/@hcm/ documents/downloadable/ucm_300338.pdf

6. Natural Clotting • Natural clotting is necessary to stop bleeding but a medical pre-disposition to clotting can present a health problem or lead to medical complications • Post-Operative blood clots can prove fatal and why they get you up and moving as soon as possible after surgery • Added Risk Factors of Age, Obesity, Heart Disease set the table for a Perfect Storm or Medical Cascade of Problems

7. http://www.mayoclinic.org/

8. Atrial Fibrillation • Irregular heart beat where heart’s upper chambers (Atria) are out of sync with lower chambers (Ventricles) • Undetected or Untreated it can lead to blood clots and complications from blood clots traveling to other organs or parts of the body

9. • Age increases risk • Heart Disease • High Blood Pressure • Family History • Obesity • Alcohol Use - Binge Drinking • Chronic Conditions Risk Factors for AFib

10. • Diagnosis may involve several tests • Electrocariodgram (ECG) • Portable ECG or Holter Monitor over period of time • Echocardiogram • Blood Tests AFib Diagnosis

11. • Damage to the Heart • Heart Attacks • Coronary Artery Disease • Abnormal HeartValves • High Blood Pressure • Congenital Heart Defecs • Metabolic Imbalance • Viral Infections • Lung Disease • Prior Heart Surgery • Sleep Apnea • Stress Illness, Surgery or Pneumonia Potential Causes

12. • WARFARIN/COUMADIN (also known as Jantoven, Marevan and Uniwarﬁn) used as anticoagulant since the 1950’s • Originally introduced in late 1940’s as rat poison or pesticide • Remains a widely prescribed and popular anticoagulant • Onset of anticoagulant qualities is not immediate • Known to Interact with other common medications • Requires dietary restrictions because it interacts with leafy foods or greens with large amounts ofVitamin K • Requires regular or routine blood test monitoring to maintain therapeutic range of dose • INR (International Normalized Ratio) Too High = Risk of Bleeding Too Low = Risk of Blood Clot • Therapeutic Range - Balancing Act • Risk of Hemorrhage/Bleeding Exists Historical Backstory

13. Emergent Solution - Antidote • Reversal Agent is known • There is a Known and Time Proven Antidote • Fresh Frozen Plasma • Vitamin K with Prothrombin Complex Concentrate • Vitamin K Intravenously

14. New Oral Anticoagulants - NOACs Marketing Message & Appeal For the Masses

15. New & Improved - One Dose Fits All

16. • PRADAXA (dabigatran etexilate) • Boehringer Ingelheim Pharmaceuticals, Inc. - Ridgeﬁeld, CT • XARELTO (rivaroxaban) • Janssen Pharmaceuticals, Inc. - Titusville, NJ • Bayer Healthcare AG - Leverkusen, Germany • ELIQUIS (apixaban) • Briston-Myers Squibb Company - Princeton, NJ • COUMADIN - Registered Trademark Holder • Pﬁzer Inc. - NewYork, NY Novel Anticoagulants Fueled By Race to Market

17. PRADAXA 1st Novel Anticoagulant inYears • Parallel Marketing Themes • No Monitoring • No Dietary Restrictions • Lifestyle Message like birth control

18. XARELTO - Market Share Heir Apparent • Parallel Marketing Themes • No Monitoring • No Dietary Restrictions • Lifestyle

19. Safety Signals & Red Flags • International Safety Signals - PRADAXA • PRADAXA Litigation • $650M Settlement • BMJ Investigative Report on PRADAXA based on litigation records and information • XARELTO • July 1, 2011 - New Oral Anticoagulant (NOAC) DVT & PE post-op knee/hip • November 4, 2011 - Non-valvular AFib • FDA’s MedWatch • U.S. Food & Drug Administration’s Adverse Event Reporting System (FAERS) • Voluntary Reporting • Companies Required to investigate those they learn about • Cornerstone/Foundation • Gaps in System

20. January/February 2013 - WebMd Magazine

21. June 6, 2013 - Untitled FDA Letter

22. http://www.bmj.com/content/349/bmj.g4670.full.pdf+html July 2014

23. August 2014

24. Broad Base of Indications

25. Prescribing Information - Major Changes

26. XARELTO MDL NO. 2592 IN RE: XARELTO (RIVAROXABAN) PRODUCTS LIABILITY LITIGATION • JPML Transfer Order 12/12/14 • United States District Court Eastern District of Lousiana • MDL No. 2592 • The Honorable Eldon E. Fallon • Experienced, well versed in MDL with ability and willingness to manage case • VIOXX; Chinese DryWall • Magistrate Judge North • Approximately 550+ cases with more anticipated

27. http://www.laed.uscourts.gov/Xarelto/Orders/Orders.htm • Pre-Trial Orders • Direct Filing • Joint Complaints • Plaintiff Fact Sheet • Defendant Fact Sheet • Science Day - June 2015 • Common Beneﬁt Order - Pre- Trial Order No. 8

28. Defendants

29. Multi-Count Complaint • Count I - Strict Liability • Count II - Manufacturing Defect • Count III - Design Defect • Count IV - Failure To Warn • CountV - Negligence • CountVI - Breach of Express Warranty • CountVII - Breach of Implied Warranty • CountVIII - Negligent Misrepresentation • Count IX - Fraud • Count X -Violation of Consumer Protection Laws/Consumer Fraud Laws • Count XI - Loss of Consortium • Count XII - Wrongful Death • Count XIII - Survival Action • Count XIV - State Speciﬁc (ie. FL Total Permanent Impairment of Parent) • Jury Trial Demand

30. • Serious bleeding events and some XARELTO Fatalities • 2,081 SAE MedWatch Reports with FDA in 2012 • Likely underreported as system if voluntary not compulsory and notorious for blind spots • At least 151 Deaths • $2B in Sales in 2013 • RECORD Studies design ﬂaw and in manner conducted • “Systematic discarding of medical records” and thus unreliable P54 • ROCKET AF study compared to warfarin. Poorly managed group and made it look “non-inferior” • Cases Filed in MDL growing over 500+ • Science Day was last week • Document review underway

31. Appoints PSC Leadership

32. XARELTO - Philadelphia, PA

33. CNN - Ad 2015

34. 2015

35. May 2015 - Paid Search

36. http://www.ﬁercepharmamarketing.com/story/should-eliquis-surge-make-xarelto- fans-very-very-afraid-not-really-analyst/2015-05-18 May 18, 2015

37. Case Acquisition • Traditional sources: • TV, Print, Radio & Web • Referrals • Co-counsel • Neighbors (Literally) • Friends & Family • Demographic & Illness Driven • Screen carefully • Proof of Use • Latency/Onset • Other Medications in Use • Adverse Event or Side Effects being litigated • Bleeding Events • XARELTO Fatalities • Gastrointestinal Bleeding

41. July 27, 2015 - Risperdal Webinar

Xarelto Fatalities Update 2015

Gabriel F. Zambrano

Xarelto Fatalities Update 2015