Stephanie Fox-Rawlings, PhD, National Center for Health Research, November 14, 2019
Thank you for the opportunity to speak today on behalf of the National Center for Health Research. I am Dr. Stephanie Fox-Rawlings. Our Center analyzes scientific and medical data to provide objective health information to patients, health professionals, and policy makers. We do not accept funding from drug and medical device companies, so I have no conflicts of interest.
Drugs to help reduce the risk of cardiovascular events save lives. The REDUCE-IT study provides encouraging data that AMR101 [Vascepa (icosapent ethyl) ] may help, but there are some important concerns that must be addressed before approval [for this new indication].
Let me start by commending the sponsors for studying more than 8,000 patients for a median of 4.9 years.
Unfortunately, the sponsor provided only one phase 3 clinical trial studying MACE [cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, unstable angina requiring hospitalization, and coronary revascularization]. As we all know, replication is the key to scientific evidence. Independent clinical trials could have a smaller or larger effect due to differences in patient demographics, comorbidities, as well as other factors. For example, there was a statistically significant effect for men, but not for women. The trend was close to significant for women, but close doesn’t count. Without a second study, it is impossible to know if this treatment is effective for women.
We share the FDA’s concern that the placebo may have interacted with statin absorption because this could have affected the rate of cardiovascular events. While the FDA analysis suggested that the effect was estimated to be small, we can’t know how completely the FDA was able to estimate all the ways that this interaction could affect cardiovascular risk.
The mission of the FDA is to provide patients with real, clinically meaningful benefits and that these benefits outweigh the risks. In this case, at least some participants taking the drug had an increased risk for adverse events such as atrial fibrillation or atrial flutter and for bleeding. It is important that the reduction in risk for cardiovascular events outweighs these risks for harm.
As advisors to the FDA, it is essential that you speak on behalf of patient safety as you carefully consider the data available for how this drug could help or harm patients. We agree with the FDA that the indication is too broad, because it would include patients who were not studied in the phase 3 trial. If you believe that the FDA should grant approval, we respectfully urge you to limit the indication to a more appropriate population.
The Endocrinologic and Metabolic Drugs Advisory Committee voted 16 to 0 in favor of approval of a new indication to reduce the risk of cardiovascular events as an adjunct to statin therapy. You can read more about the meeting here.