The American Heart Association meeting has opened with some good news for The Medicines Company of the USA after full data from a discontinued late-stage programme suggest that the investigational antiplatelet agent cangrelor is still “a highly attractive drug candidate”.
In May this year, TMC pulled two Phase III trials of cangrelor, which consisted of over 13,940 patients, because the compound did not show superiority to Sanofi-Aventis/Bristol-Myers Squibb’s blockbuster Plavix (clopidogrel) given orally for the pre-specified primary endpoints, ie reducing death, heart attack, or ischemia-driven revascularisation at 48 hours. However complete data from the CHAMPION trials, presented at the AHA meeting in Orlando, has revealed “strong evidence of pharmacological effects, clinical effectiveness and suitable safety in patients undergoing percutaneous coronary intervention” of cangrelor, which is taken intravenously.
In fact, TMC said, cangrelor significantly reduced the composite endpoint of death, Q-wave myocardial infarction and IDR (39% lower than 600mg clopidogrel). Presenting the data, Deepak Bhatt, chief of cardiology at the Veterans Administration Boston Healthcare System, said that although these composite endpoints “were devised post-hoc” and so cannot be deemed conclusive, “they are biologically plausible and suggest superior antiplatelet effects and clinical potential.”
Also presenting, Robert Harrington, professor of medicine at Duke University Medical Center, said that “the platelet sub-study of the CHAMPION PCI trial provides evidence of rapid, potent antiplatelet effect”. This is particularly important, he added, in specific patient groups, “such as those urgently requiring PCI or surgery, those who cannot receive oral medication (such as Plavix) and those who are known not to respond well to clopidogrel.”
TMC’s chief executive Clive Meanwell said the firm hopes to plan additional large clinical studies after completing discussions with regulators in the USA and starting such talks with their counterparts in Europe. It will continue enrolment in the BRIDGE study – a trial testing cangrelor, licensed from AstraZeneca in December 2003 as a platelet inhibitor in patients with coronary stents who need to discontinue clopidogrel prior to planned surgery.
An editorial in the New England Journal of Medicine, which also published the data, was very positive. It asks whether cangrelor was “given an optimal chance to show its assumed advantages”, adding that “a better study design should probably be used in the future”.
The article, authored by Adnan Kastrati and Gjin Ndrepepa of the German Heart Institute at the University of Munich, goes on to say that the drug is a potent intravenous adenosine diphosphate-receptor antagonist with a rapid onset and offset of action and “these valuable qualities certainly warrant further study aimed at identifying more suitable clinical niches for cangrelor and more appropriate approaches to its use”.
