The Medicines Company announced that the data from 13,941 patients treated in the discontinued CHAMPION Phase III program of cangrelor.
CHAMPION program data were analysed after the program’s discontinuation in May 2009 when 98% of targeted patients in CHAMPION PCI and 84% in CHAMPION PLATFORM had been enrolled. At that time, the program’s independent interim analysis review committee reported to the company and the principal investigators that the CHAMPION PLATFORM trial was not expected to meet its primary endpoints.
Cangrelor was superior to clopidogrel (600mg given orally before PCI) in inhibiting platelet aggregation measured by a range of laboratory tests (p-value < 0.0001) during the first 2 hours of treatment, resulting in more rapid and greater effect than that of clopidogrel.
The risk of the composite endpoint of death, Q-wave MI or IDR was 39% lower on cangrelor than on 600mg clopidogrel given immediately before or immediately after PCI (p-value = 0.0049). Similarly, the risk of the composite endpoint of death, Q-wave MI or stent thrombosis was 45% lower (p-value = 0.0028).
In CHAMPION PCI, cangrelor was not superior to 600mg clopidogrel loading dose in the 37% of patients who entered the trial on clopidogrel maintenance therapy. However, cangrelor was superior to a 600mg clopidogrel loading dose in remaining 63% thienopyridine-nave patients with a relative risk reduction for death/Q-MI/IDR of 43% (p-value = 0.04). In CHAMPION PLATFORM, all patients were thienopyridine-nave and cangrelor showed a relative risk reduction for death/Q-MI/IDR of 45% (p-value = 0.0028).
There was no significant increase with cangrelor in usual measures of bleeding, including no increase in TIMI major or minor bleeding; no increase in GUSTO severe or moderate bleeding; and no increase in the incidence of blood product transfusions. Access site hematomas were more frequent in patients on cangrelor than on comparators. Infrequent (~1%) and reversible episodes of breathlessness were also reported more frequently among patients given cangrelor.
Clive Meanwell, chief executive officer of The Medicines Company, said: “We are very excited by cangrelor’s promising pharmacological data, substantial improvement of important clinical endpoints, and suitable safety. It is important that cangrelor was superior to a 600mg clopidogrel loading dose in thienopyridine-nave patients. Our market research and CHAMPION PCI data show that this is the majority of patients undergoing PCI.
“We intend to continue our dialogue with the FDA and initiate discussions with European regulators to devise the most efficient and expeditious development path forward. We will be able to plan additional large clinical studies as well as timelines for cangrelor reaching the market after completing discussions with the regulators. In the meantime, we will commit resources to regulatory submissions and preparation of commercial-scale manufacturing. “
The company will continue enrolment in the BRIDGE study – a trial testing cangrelor as a platelet inhibitor in patients with coronary stents who need to discontinue clopidogrel prior to planned surgery. The company also will initiate various other clinical pharmacology studies.