Amarin Corp Plc (AMRN)

[studythosestocks]

Probably already posted but this will be the main discussion points on Thursday IMO:
From FDA Briefing Docs:

The applicant is seeking an indication for Vascepa as an adjunct to statin therapy in adult patients with elevated triglyceride levels (TG >135 mg/dL) and other risk factors for CVD, but the trial inclusion criteria and data do not appear to support such a broad population.

The trial provides strong evidence that AMR101 is beneficial in patients with established CVD and persistently elevated triglycerides despite optimized statin therapy, as these patients accounted for about 70% of the patients in the trial. While it appears that AMR101 is also beneficial in a subset of patients aged 50 or greater with diabetes, additional CV risk factors, and hypertriglyceridemia (despite optimized statin therapy), it is arguable how broadly this second population should be drawn.



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The applicant’s proposed indicated population is notably silent on several issues including appropriate patient age, presence of established CVD, presence of diabetes in patients without established CVD, statin intensity, and resulting LDL-C levels on therapy.

The planned population in REDUCE-IT was considerably narrower than the proposed indicated population. To this point, the trial had three key inclusion criteria: • Fasting triglyceride >200 mg/dL (following the first protocol amendment in 2013) • LDL-C >40 mg/dL but <100 mg/dL on stable statin therapy • Established CVD or high risk for CVD recruited in 2 risk cohorts

Cohort 1 was planned to account for 70% of patients in the trial, and included patients aged 45 and older with established CVD (diagnosed due to prior CV event, revascularization procedure, or imaging study). Cohort 2 was planned to account for 30% of the trial population, and included men and women aged 50 and older with diabetes mellitus and one or more additional risk factors (such as age, smoking, hypertension, retinopathy, and albuminuria).

Baseline characteristics suggest that the actual trial population was narrower than defined. For example, although as planned, 30% of the total population met enrollment criteria per the Cohort 2 definition, baseline characteristic data reveal that: • 99% of patients had diabetes • 95% had hypertension or were taking antihypertensive medication • 68% met age criteria for an additional risk factor

Therefore, most patients in Cohort 2 had diabetes plus at least two additional risk factors, as defined. Additionally, the rate of established CVD in the diabetes cohort was not insignificant, including patients with prior MI, stroke, and revascularization.

Furthermore, not only did most patients had baseline triglycerides 200 mg/dL or greater but approximately 72% were 175 mg/dL or greater, significantly higher than the proposed threshold of 135 mg/dL. More importantly, these triglyceride levels were achieved in a population in which 88% of patients were on either moderate- or highintensity statin therapy with adequate control of LDL-C.

In summary, the trial population represents a higher risk group than the proposed indicated population, encompassing patients with diabetes and additional risk factors, and hypertriglyceridemia despite optimized statin therapy. There is no evidence in REDUCE-IT that AMR101 is the appropriate therapy in lower-risk patients who may have elevated LDL-C in addition to mild hypertriglyceridemia and who would benefit from optimization of statin therapy first.