A decision for icosapent ethyl's sNDA is not expected to come from the FDA until September, but excitement surrounding the drug is at all-time high.
With Amarin filing a Supplemental New Drug Application (sNDA) with the US Food and Drug Administration (FDA) in late May and a decision expected by Sept. 28, icosapent ethyl (Vascepa) has captured the attention of physicians in an array of specialties.
The submission of the sNDA comes on the heels of the March submission of REDUCE-IT trial results and the potential of icosapent ethyl for diabetes patients has dominated many discussions in the hallways of the American Diabetes Association (ADA) 2019 Scientific Sessions in San Francisco, CA.
The trial, which involved more than 8,000 patients, found that icosapent ethyl showed a 30% reduction in total cardiovascular events compared to placebo in the statin-treated population studies. Investigators found that icosapent ethyl reduced total events by 30% compared to placebo. These results reflected that for every 1000 patients treated for 5 years, approximately 159 major adverse cardiovascular events could be prevented. Study authors also noted a 28% reduction of total events in the study’s key secondary endpoint of 3-point major adverse cardiovascular events in the intent-to-treat population.
At ADA 2019, Robert Busch, MD, director of clinical research in the Albany Medical Center Endocrine Group, led an Amarin-supported review on the topic of the REDUCE-IT findings both as they pertain to the supplemental application for icosapent as well as its current adjunct hypertriglyceridemia treatment indication.
MD MAG: What are the clinical implications of the REDUCE-IT trial and the efficacy of icosapent ethyl?
BUSCH: So, REDUCE-IT trial is a cardiovascular outcome trial for primary prevention, patients with diabetes who don't have known cardiac disease but they have risk factors for cardiac disease and that was 30% of the study and 70% of the patients already had an atherosclerotic event — either an MI or a stroke or some other atherosclerotic event. So, to get into the study you had to have high triglycerides over 135, which isn't that high but still elevated. You had to be on a statin, so you were already on standard of care in terms of cardiac protection with a statin with an LDL that was below 100 — it had to be 40 to 99 and that basically got you into the study.
What's so interesting to me as an endocrinologist and my peers is you could have diabetes and a risk factor, diabetes and hypertension, diabetes and being a male over 55 or a female over 65, or diabetes and a low HDL, or diabetes and smoking. So, basically these patients are who are in front of us every day when we are practicing. Of the patients with heart disease who got in, many of those had diabetes.
So overall, the study had about 58% of patients with diabetes and 30% diabetes and risk factors, 70% cardiac disease but they could have had diabetes. That was the setup of the study but what your buy-in to the study was you had to have a triglyceride over 135 as a signal of additional cardiac risk. The reason that is a signal was previous studies have shown that if your triglycerides are elevated you are at higher cardiac risk.
The importance of the study is no other drug ever showed that by adding it to patients with high triglycerides there was cardiac benefit. So, the other two big drugs that have been tested in the past, niacin and fibric acid, did not have positive outcomes.
So, going into this study the hope would be positive but it was uncharted territory. Other omega-3 studies also did not show cardiac benefit. So, the bottom line of the study — the study was continued about 6 years, there was almost 8,000 something patients — half on the Vascepa and half on placebo and the bottom line is that the primary endpoint, which was lowering non-fatal MI, non-fatal stroke cardiac death, cardiovascularization, or unstable angina hospitalization went down 25%. That was the primary end point — that was announced before last November.
At the heart meetings last November, Dr. Bhatt, of Brigham and Women's Hospital, who was the study's lead author announced the other data — 26% lowering of what is called hard MACE — Nonfatal MI, nonfatal stroke and death and each separate outcome, nonfatal went down 31%, stroke went down 28%, and cardiovascular death down 20%. So, what's so unique about the study is not only was it a positive study but each specific end point in itself drove the outcome. Each one was statistically significant as was the overall outcome.
In terms of side effects, the side effects were 3 that were more than placebo. Peripheral edema without heart failure, mild constipation, and there were higher rates of hospitalizations for atrial fib but there was a lower rate of stroke so the atrial fib was there unknown why, but it did not lead to stroke, there were less strokes by 28% in the Vascepa group.
So, that's pretty much what the study showed. In terms of impact on us as a prescribing physician, we see patients with diabetes every day with risk factors and the triglycerides is often ignored. Now, looking at the triglycerides you’re going to do something about it. It's an obligation to say look I want to lower my patients MI, stroke, death give Vascepa not a dietary supplement fish oil and not any of the other drugs that lower triglycerides that have not been shown to have benefit but this shows very compelling evidence that it's very beneficial.
MD MAG: Do you see use of icosapent ethyl becoming a standard of care in treatment of diabetes?
BUSCH: I think with the data the way it is, the American Diabetes Association has already authorized it as standard of care even before it goes to the FDA in September to get its final blessing. The paper was announced in November, the New England Journal lead article was felt to be the most important cardiology article of the year for all of last year, in March at the heart meetings they announced that total events, not just first event went down 30%. So, suppose you had a stroke and you lived, it still prevented the MI or other things like that.
So, total events went down and if I had to guess, I can’t see why they wouldn't approve it with such striking data. With each individual endpoint MI and stroke and death and the 5-point MACE as well. So, my hope is it would be approved and I hope that my colleagues do what I'm doing after seeing the data. I'm looking at triglycerides as an obligation to utilize the drug.