Will Next Generation Oral Anticoagulants Replace Warfarin as Mainstay Therapy?



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Brochure More information from http://www.researchandmarkets.com/reports/1869007/ Will Next Generation Oral Anticoagulants Replace Warfarin as Mainstay Therapy? Description: Will Next Generation Oral Anticoagulants Replace Warfarin as Mainstay Therapy? Pradaxa: With a first mover advantage, Will it be the Leader in SPAF? Xarelto: Is it the future mainstay anticoagulant therapy? Eliquis and Edoxaban: Would they be able to differentiate enough? In the coming months, there are major regulatory and clinical milestones with regard to the new generation of oral anticoagulants (Pradaxa, Xarelto, Eliquis and Edoxaban), which will have wide ranging impact on the treatment paradigm in several therapeutic areas encompassing - stroke prevention in atrial fibrillation / DVT Treatment / VTE prevention in medically ill patients and Acute coronary syndrome. Stroke prevention in atrial fibrillation (SPAF-Chronic therapy) is the largest potential market and we forecast upto $5b in peak sales for the new generation anticoagulants. SPAF affects about 4.5m people in the EU and 2.2m in the US. Existing clinical data on Pradaxa, Xarelto and Eliquis is not differentiated enough and as well not comparable due to differences in clinical trial design and endpoints. However upcoming milestones new clinical data and regulatory decisions would largely fix the competitive landscape, which will eventually evolve based on physician experience, regulatory scenario and entry of new drugs. Among the other late stage pipeline candidates Daiichi's Edoxaban is most promising. There are also other important pipeline drugs which are in early stage development and pose threat to the potential of Xarelto/Eliquis/Pradaxa in the longer term. In SPAF our forecast is driven by a number of factors which would influence the treatment decisions in the near term and longer term. - Warfarin Genotype testing, its regulatory approval and its reimbursement - Warfarin discontinuers - Impact of dosing frequency on treatment practice in SPAF - Patient's history of stroke and bleeding risk factors impacting treatment decision - Concomitant Medicines- Affordability and drug-drug interaction - Regulatory Scenario Medicare Shared Saving program to be implemented in 2012 - Physician's Experience and cost effectiveness Acute Coronary Syndrome (6 month therapy) Does Xarelto has the potential to compete Brilinta? ACS is the next largest potential market for the next generation anticoagulants, while Eliquis has failed in the PhIII ACS study on account of higher bleeding rates, but the ATLAS-TIMI trial exploring Xarelto is ongoing and data should be available by YE 2011. In the PhII trials, Xarelto has demonstrated robust clinical benefit over standard of care at both the doses (2.5mg - twice-daily & 5mg- twice-daily dose), which are currently being explored in Ph-III ATLAS-TIMI trial. We foresee Xarelto as a serious contender in the ACS space and should impact Brilinta potential. There are many ongoing trials, which will show data over the next two years and will have implications on the treatment paradigm in ACS. VTE prevention in medically ill patients- Xarelto is unlikely to make it, Eliquis is the next one to watch out for (6 month therapy): This represents about 55% of the Lovenox use and hence is a major opportunity for the next generation anticoagulants. Demonstrating benefit over Lovenox on efficacy in the medical prophylaxis setting, without

increasing the risk of bleeding is a high hurdle. The data from ADOPT study exploring Eliquis in VTE prophylaxis in medically ill patients is around the corner, but in terms of expectations we remain on the sidelines due to efficacy concerns. Xarelto has failed in the MAGELLAN study, as increase in bleeding outweighed the benefit of reduction in clots. DVT/PE treatment (3-12 month therapy): This therapy represents a $3billion opportunity for the new generation anticoagulants. The DVT/PE treatment opportunity is not easy to guess, as the optimal duration of therapy is still a grey area. The D- dimer test which is currently used as a marker to decide on whether to continue therapy is associated with a 4% fatality rate. Both Xarelto and Pradaxa have demonstrated non-inferiority over warfarin in PhIII trials EINSTEIN-DVT and RECOVER study respectively. Although the two trials are not comparable, but taking a clue from total evidence available in the VTE prevention/treatment trials, Xarelto obviously appears to be best poised as the new mainstay treatment for DVT. A number of studies (RECOVER 2 Pradaxa, AMPLIFY- Eliquis and EINSTEIN-PE Xarelto and HOKUSAI- Edoxaban) are ongoing in DVT/PE treatment. This therapy class report analyses the practical issues in the adoption of new generation anticoagulants, major upcoming milestones, clinical trial design/data and cost-effectiveness of recently launched and upcoming molecules. This report will provide insightful information about the performance of molecules in oral anticoagulation arena in all the indications (SPAF, VTE, ACS) and the way these newer drugs will be positioned to garner the benefits against Aspirin/Warfarin/Lovenox are discussed. Contents: 1. ANTICOAGULANTS MARKET - Market size and Segmentation By Drugs and Indications - Current therapies - Factor Xa Vs. Direct Thrombin inhibitor - New generation anticoagulants pipeline - Major Upcoming Milestones - Estimated launch timelines for new generation anticoagulants Indication wise 2. STROKE PREVENTION IN ATRIAL FIBRILLATION - The Current Market Dynamics- Geographywise prevalence of SPAF and treatment paradigm of anticoagulation therapy in SPAF - Does higher unmet need prevail in high risk (CHADS2 score) patients or low risk patients? - Experts view on the hurdles to the adoption of new generation anticoagulants in SPAF - The need for new generation anticoagulants - Factors that will influence the choice of anticoagulation therapy in Atrial Fibrillation Regulatory and Clinical Warfarin Genotype testing, its regulatory approval and its reimbursement Warfarin discontinuers Impact of dosing frequency on treatment practice in SPAF Patient's history of stroke and bleeding risk factors impacting treatment decision Concomitant Medicines- Donut hole and drug-drug interaction Regulatory Scenario Medicare Shared Saving program to be implemented in 2012

Physician's Experience and cost effectiveness - Warfarin continues to hold itself strong against Pradaxa Will the entry of Xarelto / Eliquis / Edoxaban change the scenario? - Highlights of AVERROES, RELY and ROCKET AF Studies - AVERROES trial rationale and results No commercial implications - Baseline and Trial Design comparisons RELY, ROCKET AF AND ARISTOTLE - Overall Efficacy and Safety comparison ROCKET, RELY AND AVERROES - Efficacy and safety comparison in high risk patient's population - What to expect from the detailed data of ARISTOTLE (Eliquis) at ESC - FDA Advisory Committee's The Key Questions on Xarelto for approval in SPAF - Will the Label be comparable to Pradaxa? - Universal antidote for novel oral anticoagulants - The Future Mainstay Treatment In SPAF - Xarelto Or Pradaxa Or Eliquis 3. ROLE OF NEW GENERATION ORAL ANTICOAGULANTS IN VTE PREVENTION IN ORTHOPEDIC SURGERY - Prevalence of VTE after Total Hip Replacement Surgery / Total Knee Replacement Surgery - The need and importance for extended prophylaxis and current limitations - Clinical data comparison Xarelto, Eliquis and Pradaxa - Compliance benefits provided by oral anticoagulant justify higher annual cost of therapy to Lovenox or not? 4. ROLE OF NEW GENERATION ORAL ANTICOAGULANTS VTE PREVENTION IN MEDICALLY ILL PATIENTS - Market segmentation based on Illness - Incidence Of DVT In Orthopedic Surgery Vs. Acute Medically Ill Patients - VTE Prevention in Cancer Patients VTE incidence rates in different types of cancer - Ongoing clinical studies - Xarelto Review of MAGELLAN study - Eliquis ADOPT Study - Semuloparin - Clinical data comparison Of VTE prophylaxis in cancer Patients 5. ROLE OF NEW GENERATION ORAL ANTICOAGULANTS VTE TREATMENT - New Generation anticoagulants will expand the DVT treatment opportunity manifold - Pradaxa - RECOVER study - Eliquis - BOTTICELLI Study and AMPLIFY study - Xarelto EINSTEIN DVT study - Xarelto EINSTEIN EXT study

- Xarelto Other Ongoing studies - Edoxaban HOKUSAI study - Clinical data comparison from DVT treatment studies 6. FACTOR XA INHIBITORS- DO THEY HAVE POTENTIAL TO BE AN IDEAL ANTICOAGULANT FOR SECONDARY PREVENTION OF ACS? - Historically anticoagulant have failed to show a positive risk-reward profile in ACS - Xarelto is likely to be an exception - Clinical data comparison of Anticoagulant as add on to current ACS treatment vs. Newer Antiplatelets agent - Upcoming clinical data newsflow which has potential to change market dynamics 7. WHO IS BETTER POSITIONED IN EARLY STAGE FACTOR Xa INHIBITORS? - YM150 - LY517717 - Eribaxaban - Betrixaban - TAK-442 8. HOW THE NEXT GENERATION ORAL ANTICOAGULANTS WOULD STACK UP? ANNEXURES - Goals of Anticoagulation therapy - Current Anticoagulation - Market Segmentation by drugs and Indication - Characteristics of an Ideal Anticoagulant - New Generation Anticoagulant Pipeline - Clinical profile a) Rivaroxaban b) Dabigatran c) Apixaban d) Edoxaban e) Betrixaban f) Other Early Stage Compounds- YM 150, TAK 442 - Preclinical profile of Eliquis, Pradaxa and Xarelto - Pharmacokinetic/dynamic comparison of Factor Xa inhibitors/direct thrombin inhibitor vs. Warfarin - Clinical Data comparison of major anticoagulants in VTE prevention - Prevalence of VTE after Total Hip Replacement Surgery / Total Knee Replacement Surgery - VTE Incidence in patients taking prophylaxis Vs. Those not taking prophylaxis post Discharge - Rate of Fatal PE Emboli and DVT In different categories of Medically Ill Patients - Reported VTE incidences In Various types of Cancer

- Comparison of Clinical data from Trials Prevention of VTE in cancer Patients - Clinical Data comparison major anticoagulants in DVT treatment - Clinical Data comparison major anticoagulants in ACS Liver Toxicity Long term safety concern: Liver Toxicity Assessment of Bleeding Risk - Clinical Data comparison - Stroke Prevention In AF Studies (edoxaban, betrixaban, Pradaxa, Exanta, Warfarin, aspirin, Eliquis, Xarelto) - Stroke Prevention in Atrial Fibrillation Market segmentation by drug usage - Baseline Characteristics Comparison Of Pivotal Trials In SPAF ROCKET, RELY, ARISTOTLE and AVERROES - Reimbursemnt status of PT/INR monitoring for warfarin in major countires - Estimated launch timelines for new generation anticoagulants Indication wise - PhIII Trial Design of late stage Factor Xa Inhibitors for Stroke Prevention in AF - Mortality Rate in Atrial Fibrillation By Gender and Age - Stroke Rate Per 100 Patient Years Increases Substantially With CHADS2 Score - Reported VTE Incidences In Various Cancer - Incidence Of DVT In Orthopedic Surgery Vs. Acute Medically Ill Patients - Risk / Incidence of DVT and Fatal PE in different categories of Medically Ill Patients - Ongoing Clinical trials in ACS, whose outcome will have significant implications on the treatment paradigm and market potential - Upcoming Milestones New Generation Anticoagulants Ordering: Order Online - http://www.researchandmarkets.com/reports/1869007/ Order by Fax - using the form below Order by Post - print the order form below and send to Research and Markets, Guinness Centre, Taylors Lane, Dublin 8, Ireland.

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