Amarin announced Monday that a prespecified analysis of US-enrolled patients in the REDUCE-IT cardiovascular (CV) outcomes trial showed that Vascepa (icosapent ethyl) was associated with "robust" risk reductions versus placebo across all composite and individual primary and secondary endpoints. These include a 31% relative risk reduction and 6.5% absolute risk reduction in first occurrence of five-point major adverse cardiovascular events (MACE), as well as a significant 30% relative and 2.6% absolute risk reduction in all-cause mortality.
Chief scientific officer Steven Ketchum said the latest REDUCE-IT findings, which were published in the journal Circulation and are scheduled for presentation at the upcoming American Heart Association (AHA) conference, "are further evidence of the robust and consistent nature of this landmark study and its applicability to typical clinical practice in the US." He added that the results also support the idea that "persistent CV risk beyond cholesterol management can be significantly reduced with Vascepa in the high-risk patient population studied in REDUCE-IT."
The US subgroup of the REDUCE-IT trial consisted of 3146 patients, or 38.5% of the full trial cohort, which enrolled adults already on stable statin therapy, but who still had elevated triglyceride levels and either CV disease or diabetes with other CV risk factors. Patients were randomised to receive Vascepa twice daily or placebo containing mineral oil, and were followed for a median of 4.9 years.
Amarin noted that placebo patients in the US subanalysis had a higher primary endpoint event rate compared with the full cohort, at 67.4 versus 57.4 per 1000 patient-years, respectively. The primary five-point MACE endpoint occurred in 18.2% of US Vascepa-treated patients, compared with 24.7% for placebo, while for the key secondary endpoint measuring three-point MACE, the rates were 12.1% and 16.6%, respectively, representing a 31% relative risk reduction.
Vascepa was also associated with significantly lower rates on all prespecified hierarchical primary and secondary endpoints versus placebo, including myocardial infarction, CV death, stroke and all-cause mortality. However, Amarin noted that "there was a trend towards a reduction in all-cause mortality" in the full study cohort, where each of these other primary and secondary endpoints also achieved statistical significance. Meanwhile, safety findings in the US subgroup were consistent with observations in the full cohort.
Amarin cautioned that "REDUCE-IT was not specifically powered to examine individual subgroups," suggesting that "differences in efficacy outcomes for US patients are best viewed as qualitative and not quantitative." Still, the drugmaker claimed the "data are useful and provide reassurance that the results in the US are at least as strong as the results seen outside the US and in the trial overall."
In results reported last November, Vascepa was shown to be associated with a relative risk reduction of 25% in first occurrence of MACE on the five-point primary composite endpoint, whilst meeting the key secondary goal of a 26% relative risk reduction in three-point MACE in the intent-to-treat population, including a 20% reduction in the risk of dying of heart disease. Principal investigator Deepak Bhatt said the most recent findings "are also remarkable when you consider that in some multi-national CV trials, patients in the [US] experience less benefit."
Vascepa was cleared by the FDA in 2012 to reduce triglyceride levels in adults with severe hypertriglyceridaemia. Earlier this year, the agency granted priority review to a filing seeking to broaden Vascepa's label to include reducing the risk of MACE. An advisory panel is scheduled to meet on November 14 to determine whether to back the label expansion based on the REDUCE-IT data, with an FDA decision expected by the end of December.
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