Amarin Corp Plc (AMRN)

[Atom0aks]

Will Lar...

Quote..."Thanks for sharing the calculation. Interesting. The numbers used in the math are for the primary events which I thought are non-fatal events. The secondary events include cv death and others and the risk % is even smaller, e.g., 3.5%?"

Once again you demonstrate why you should be listening and not educating...

Obviously you do not understand what is meant by primary and secondary events...The distinction has nothing to do with severity of the event...Primary events are events seen in patients who have no documented history of CVD...That is have not had a previous event like an MI, an ischemic stroke...or even Angina requiring hospitalization...A primary event can be a fatal MI...Secondary events are those occurring in patients that do have a documented history of CVD,,,such as a previous heart attack, stroke or a coronary intervention..From a trial standpoint events are much more commom in secondary patients because they have known CVD...Events are less common in primary prevention patients...

":>) JL

Sorry, I'm not quite sure what you're trying to say but I think you may be confusing several different concepts.

Based on Will Lar's message,

Atom - Thanks for sharing the calculation. Interesting. The numbers used in the math are for the primary events which I thought are non-fatal events. The secondary events include cv death and others and the risk % is even smaller, e.g., 3.5%?

In any case, the % number is small, but multiply % with Vascepa target population size can yield hundred thousands patients in US, which easily beat any cancer patient population size. It's not necessarily death, but life threatening condition for all.

But I do remember seeing a chart of likelihood of getting a priority review vs. different therapeutic areas. Infectious disease is high on the chart, whereas chronic diseases like CV, Alzheimer's are on the low end. So the fact that Vascepa sNDA was granted a priority review is already a positive thing, even though the timeline is now more link a regular review.

I think he was referring to the first paragraph of the discussion in the REDUCE-IT paper,

In REDUCE-IT, the risk of the primary composite end point of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina, assessed in a time-to-event analysis, was significantly lower, by 25%, among the patients who received 2 g of icosapent ethyl twice daily than among those who received placebo, corresponding to an absolute between-group difference of 4.8 percentage points in the rate of the end point and a number needed to treat of 21. The risk of the key secondary composite end point of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke in a time-to-event analysis was also significantly lower, by 26%, in the icosapent ethyl group than in the placebo group, corresponding to an absolute between-group difference of 3.6 percentage points in the rate of the end point and a number needed to treat of 28. Prespecified hierarchical testing of other secondary end points revealed that the risks of a variety of fatal and nonfatal ischemic events were lower in the icosapent ethyl group than in the placebo group, including a 20% lower risk of cardiovascular death. The benefits were observed against a background of appropriate statin use among patients who had a median LDL cholesterol level of 75.0 mg per deciliter at baseline.

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa1812792

In which case, I think the primary endpoint is defined as,

The set of primary endpoints consists of the outcome or outcomes (based on the drug’s expected effects) that establish the effectiveness, and/or safety features, of the drug in order to support regulatory action. When there is more than one primary endpoint and success on any one alone could be considered sufficient to demonstrate the drug’s effectiveness, the rate of falsely concluding the drug is effective is increased due to multiple comparisons (see section II.E).

Source: https://www.fda.gov/media/102657/download

The primary endpoint in the REDUCE-IT study was,

The primary efficacy end point was a composite of cardiovascular death, nonfatal myocardial infarction (including silent myocardial infarction), nonfatal stroke, coronary revascularization, or unstable angina in a time-to-event analysis.

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa1812792

And I think the secondary endpoint is defined as,

Secondary endpoints may be selected to demonstrate additional effects after success on the primary endpoint. For instance, a drug may demonstrate effectiveness on the primary endpoint of survival, after which the data regarding an effect on a secondary endpoint, such as functional status, would be tested. Secondary endpoints may also provide evidence that a particular mechanism underlies a demonstrated clinical effect (e.g., a drug for osteoporosis with fractures as the primary endpoint, and improved bone density as a secondary endpoint).

Source: https://www.fda.gov/media/102657/download

The secondary endpoint in the REDUCE-IT study was,

While the steering committee and the sponsor remained unaware of the trial-group assignments, a second protocol amendment in July 2016 designated the key secondary end point as a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke in a time-to-event analysis. After the primary efficacy end-point analysis was performed, the prespecified secondary efficacy end points were examined in a hierarchical fashion in the following order: the key secondary efficacy end point; a composite of cardiovascular death or nonfatal myocardial infarction; fatal or nonfatal myocardial infarction; emergency or urgent revascularization; cardiovascular death; hospitalization for unstable angina; fatal or nonfatal stroke; a composite of death from any cause, nonfatal myocardial infarction, or nonfatal stroke; and death from any cause.

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa1812792

Perhaps, you were thinking about primary and secondary prevention cohorts? In which case, in the REDUCE-IT study, these were,

Among the patients who underwent randomization, 70.7% were enrolled on the basis of secondary prevention (i.e., patients had established cardiovascular disease) and 29.3% on the basis of primary prevention (i.e., patients had diabetes mellitus and at least one additional risk factor).

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa1812792