We appreciate your interest in our report detailing the 2014 US Food and Drug Administration (FDA) Cardiovascular and Renal Drugs Advisory Committee Meeting regarding Cangrelor, which mirrored the meeting presentations, facts, and discussions.

We agree with the readers that the necessity of preloading needs to be addressed but, more specifically, with the newer P2Y12 inhibitors (ticagrelor or prasugrel), which were not available in the pivotal trials. In the 2014 meeting, the independent review from the FDA showed that the 600-mg preload of plavix was the most significant predictor of outcomes (and possibly explains why cangrelor was superior to clopidogrel because ∼26% of the patients in the clopidogrel arm were loaded with only 300 mg). The main question should be related to the rapid action and potency of the P2Y12 inhibitors. Most recently, crushed ticagrelor tablets were approved for use and were reported to accelerate the time to obtain adequate platelet inhibition. This raises a legitimate question of how these new agents are compared clinically with cangrelor.

Furthermore, in our report, we looked into the benefit of cangrelor during ST-segment elevation myocardial infarction, where it may be considered most useful, and as listed in Table 3 of our report, the benefit was uncertain. Nevertheless, we agree with the Sponsor that there remains an “unmet need” for cangrelor, but we see it in those patients who are not preloaded with P2Y12 inhibitors or cannot take ticagrelor or prasugrel during high-risk acute coronary syndrome. Otherwise, perhaps, it should be used as a bridge in the perioperative setting when coronary artery bypass graft surgery is anticipated or confirmed.

As alluded to in our report, the independent committee reviews and evaluates available data concerning the safety and effectiveness of marketed and investigational human drug products for use in the treatment of cardiovascular and renal disorders and makes appropriate recommendations to the FDA, but these recommendations are not binding. In the case of cangrelor, further discussions between the Sponsor and the FDA led to a second panel on April 2015, which included the presentation of new data and additional sensitivity analyses from the Sponsor. In the April 2015 meeting, the FDA reviewers gave a favorable review and said that the agent could now be considered for approval “in patients in whom treatment with an oral P2Y12 platelet inhibitor before PCI is not feasible and when glycoprotein IIb/IIIa receptor antagonists are not anticipated to be used.” FDA reviewers also accepted the results of a Clinical Trial Comparing Cangrelor to Clopidogrel Standard Therapy in Subjects Who Require Percutaneous Coronary Intervention (PCI) (CHAMPION PHOENIX) as sufficient enough as a stand-alone trial to warrant approval of cangrelor.

The readers will be pleased to know that in the April 2015 meeting the advisory panel voted in favor of approval of the agent for reducing thrombotic events in percutaneous coronary intervention. This latest recommendation will most likely lead to the approval of cangrelor for marketing in the United States without the need to conduct further studies. The final labeling, post-marketing requirements, and approval date of the agent remain to be seen.