Cangrelor is a reversible, intravenous inhibitor of the P2Y12 receptor whose effect is to inhibit adenosine diphosphate-induced platelet aggregation. The Medicines Company is developing it for use in the setting of patients undergoing percutaneous coronary intervention procedures (PCI), specifically those who have not used Plavix or other P2Y12 inhibitors in the prior week. Two previous phase III trials failed to meet their primary endpoints. Thus, approval hangs on the results of a third trial, CHAMPION-PHOENIX that should report before year-end. This report explores the probability of a favorable phase III outcome, eventual approval, and the market opportunity.
1. Acute coronary syndromes (ACS)
2. Thrombosis is at the center of causality
? Clot formation is the ‘final common pathway’ of ACS
? Platelets play an integral role in clot formation
3. Clinicians use several approaches to platelet inhibition
? Clopidogrel (Plavix, Sanofi/Bristol Myers Squibb)
? Prasugrel (Effient, Eli Lilly)
? Ticagrelor (Brilinta, AstraZeneca)
1. Phase I/II trials
2. Pivotal trials
? CHAMPION trials (Harrington RA et al and Bhatt DL et al; NEJM 2009)
? BRIDGE (Angiolillo DJ et al; JAMA 2012)
CLINICAL AND REGULATORY DISCUSSION
1. Why did CHAMPION-PCI and CHAMPION-PLATFORM fail?
? Was the sample size adequate?
? Did the definition of myocardial infarction used in the study affect the outcome?
? Did the timing of Plavix administration and/or drug-drug interactions affect results?
2. Given the PCI and PLATFORM results, what are the lessons for PHOENIX?
3. Are there meaningful safety concerns associated with cangrelor?
4. Are there any bleeding concerns?
5. Possible adverse pulmonary effects of cangrelor
6. What are the regulatory issues that cangrelor will face?
? Effient (prasugrel, Eli Lilly)
? Brilinta (ticagrelor, AstraZeneca)
7. Other relevant FDA guidance
8. In summary
1. Overview of issues
2. Market estimates
3. Pipeline products
APPENDIX 1. Phase II Cangrelor Studies
APPENDIX 2. CHAMPION Trial Designs
APPENDIX 3. CHMAMPION-PCI and Platform Bleeding Events