Last August the results of PLATO raised hopes that ticagrelor could join clopidogrel and prasugrel in the antiplatelet armamentarium. On Thursday, in the course of its quarterly update, the drug’s manufacturer, AstraZeneca, raised an issue that may dampen somewhat the positive news from the summer.
Here is the relevant portion of the AstraZeneca press release:
The PLATO trial design prospectively identified 66 subgroups including 33 efficacy and 33 safety. The findings from 62 of the 66 subgroups were consistent with the results in the overall study population. Given the large number of subgroups evaluated, the four inconsistent findings may have been due to chance. One of the four subgroups showed a difference in efficacy results between patients in North America and those enrolled elsewhere. Alongside explanation by the play of chance, this raised questions of whether geographic differences between populations of patients or practice patterns influenced the effects of the randomised treatments. While no definitive explanation has been found to date, further analyses suggest a possible association between aspirin dose and the primary efficacy results, such that reduced efficacy was observed with ticagrelor and increasing aspirin doses. The Company and the PLATO investigators are continuing to explore these and other hypotheses, as well as other follow-on analyses of the PLATO trial data set, and plan to publish in due course.
The company provided no further information at this time. On Friday November 6 the company is hosting a media briefing to discuss PLATO (and other topics) in advance of the AHA.
AstraZeneca also reported that on October 26 the MAA for Brilinta was submitted to the EMEA and said that it was on track for a 4th quarter US NDA submission.
AHA presentations regarding ticagrelor include:
- A Late-Breaker clinical trial presentation for the STEMI ACS cohort in PLATO
- First presentation of the ONSET/OFFSET Phase II study, investigating the speed of onset and offset of antiplatelet effect of ticagrelor versus clopidogrel.
- First presentation of the RESPOND Phase II study, comparing antiplatelet response of patients with ticagrelor versus clopidogrel.
Click here to download a PDF of the AstraZeneca third quarter results press release.
Click here to read the CardioBrief story this summer on the PLATO presentation at the ESC and publication in the Lancet.