Old post with Dr. Eliot Brinton's statement at ADCOM
This is one of my all-time favorite posts on IHUB regarding why Vascepa should have been approved (thanks to "go seek" post number 31045).
I'll let the post speak for itself.
DR. BRINTON: My name is Dr. Eliot Brinton, and let's see if we can go into our slides. Dr. Eliot Brinton. I'm president of the American Board of Clinical Lipidology, but I'm here not representing them but just myself as a clinician and concerned citizen.
I've been involved in academic lipidology for several decades. I'm on the REDUCE-IT steering committee. I am receiving travel reimbursement from Amarin, but this presentation is mine and not theirs. I think we need to consider more of the data on JELIS. I'm going to try to focus on things that haven't been covered yet. And this last point actually has been made very nicely by the earlier speakers.
My rationale for approving the expanded indication for Vascepa is basically the clinical trial evidence for JELIS, which is a pure EPA study, therefore very similar to and I think relevant to Vascepa.
Does Vascepa actually equal Epadel? They're both greater than 98 percent pure EPA ethyl ester. There's no known chemical difference between the two. So I think that JELIS is very relevant to the question today. You've seen that slide.
I want to just point out that the primary and secondary prevention data were very similar. The curves separate well before one year. Eighty percent of the patients were primary prevention.
To the question of MACE and hard versus soft, realize that they had three hard MACE endpoints -- sudden cardiac death, fatal and nonfatal MI. The risk reduction was identical for the hard MACE as for the soft MACE. Therefore, in my opinion, even though PROBE design open label is potentially problematic, I think that it is much less problematic than it would have been if that had not been the case. So I think it's important to realize that hard MACE was definitely reduced in this study.
Prespecified subgroup, 1,000 patients with high triglyceride/low HDL relevant to the expanded indication. Notice the increased risk in unmet need, as has been stated by others. This you've seen, but I want to point out that this was a prespecified sub-analysis of a positive trial, therefore much more solid than some of the other sub-analyses that we've been looking at.
Just to look at the risk/benefit ratio, I think, is very, very important here. There was a 2.5 percent drop in the MACE composite compared to a .5 percent increase in total hemorrhage, but there was no increase in cerebral hemorrhage. So the most dangerous hemorrhage was not increased at all.
Number needed to treat, 38 for 5 years. Number needed to harm for hemorrhage, 200. Glucose was talked about. I had not included this in my original slide because it was not statistically significant, but there was a .1 percent increase. Number needed to harm for glucose increase, 786. So I think the risk/benefit ratio here is strongly in favor of pure EPA, a.k.a. Epadel/Vascepa.
Putting in the context -- and again, this has been discussed, but to point out this is the only study at mid-dose EPA, the only study with pure EPA. DHA at best dilutes the effect of EPA. Probably harmful if there's animal evidence that it actually down-regulates the LDL receptor. So I think that's very important.
Then to the point of the treatment. My back of the envelope is a little different than your back of the envelope. I've got it down to 133. I'm not sure exactly what the number is. But that was considered controlled. They had the option to up-titrate if it was not controlled according to Japanese guidelines. And if you think about the fact that 80 percent of these patients were primary prevention, current use guidelines, the goal was less than 130.
So I think the statin treatment was pretty reasonable. A very important point is that reduction in CVD was comparable with higher versus lower LDL. So if your LDL was high, you still have the same CVD event reduction. So granted, this is suboptimal in terms of statin treatment, but in those who we would have treated more aggressively, it still seems to work very nicely.
The Japanese patients eat a lot of fish. But the benefit was seen with an EPA over 150, and there was a 100-point rise with the 1.8 gram EPA. So I think anybody that doesn't eat fish is still likely to do nicely on 1.8 grams of EPA.
With regard to the lipid changes, I know that I'm a lipidologist; we're considering lipids. But realize that the benefit was seen despite very anemic lipid changes in this study. The reduction in CVD was proportional to the on-treatment EPA level.
We know that there's a linear dose-response between dose and levels, and therefore, at 4 grams a day, which is what we're studying in the REDUCE-IT study -- I'm on that steering committee -- is I think we're going to see a greater benefit. Okay? We don't know that until we do it.
The last and most important point here is that REDUCE-IT does address what few limitations there are of JELIS. And I think, as it stands, we've got excellent data with JELIS.
So just to summarize, we've got a drug that has lipid efficacy, reducing all the major adverse lipid fractions. It has a lot of other things that we haven't talked about. And then you've heard the last part here. So I just think it's very, very important to say that we've got a drug that reduces CVD as a statin adjunct in the target population. Excellent safety. Most Vascepa use is already in that space because it's 15 times more common than TG over 500, so we're basically validating what's happening in practice, which I think is actually a good thing.
It's way better -- it's going to help us divert use, as has been said, against these dietary supplements, which are problematic; Lovaza, which has no data to speak of, and what data we have is adverse; and then the other triglyceride medications, which I think are also --
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