The Endocrinologic and Metabolic Drugs Advisory Committee (EMDAC) met on November 14th to review a supplemental New Drug Applications (sNDA) for icosapent ethyl, which is currently indicated for triglyceride reduction in patients in very high triglyceride levels. The meeting discussed the sNDA by the applicant Amarin Pharmaceuticals Ireland Limited, which would expand the label of icosapent ethyl 4g/day to include cardiovascular (CV) risk reduction in statin-treated patients with elevated risk for major CV events, including death due to a CV event, heart attack, stroke, coronary revascularization (blockage of the vascular system that requires surgery), and unstable angina (unexpected chest pain). In large population studies, several risk factors have been identified that predict major adverse CV events (MACE). Some risk factors have a greater predictive power (sensitivity) for a future MACE. A patient who has had a MACE is at a high risk of experiencing a subsequent MACE. Other risk factors, such as diabetes or elevated LDL-C, are also predictive of MACE. A patient’s risk of a future MACE is estimated as a combination of all CV risk factors.
Icosapent ethyl, brand name Vascepa, is an oral medication consisting of a highly purified form of eicosapentaenoic acid, an omega-3 fatty acid isolated from fish oil. The effect of icosapent ethyl is not entirely understood, but evidence exists for a reduction in inflammation and/or reduction in cholesterol deposits in the major blood vessels of the heart (coronary plaque regression). Previous evidence has shown that icosapent ethyl reduces elevated triglyceride levels. Although elevated triglyceride (TG) levels strongly correlate as a CV risk factor, the impact of lowering TG levels is not clear. Previous studies where TG was lowered did not lower the risk of MACE. The sNDA for icosapent ethyl is based on the large cardiovascular outcomes study, REDUCE-IT trial, which showed a reduction in MACE events in patients at a high risk of MACE treated with icosapent ethyl 4g/day compared to placebo.
This meeting was comprised of three discussion questions and one voting question. The voting question asked whether the label of icosapent ethyl should be expanded to include reduction in MACE in patients with certain CV risk factors. The committee voted 16 (YES) to 0 (NO). The panelists were compelled by the reduction in MACE events that was large in magnitude, statistically significant, and consistent across subgroups. They believed that the trial demonstrates that the benefits of icosapent ethyl outweigh the risks. Although no panelists voted “NO”, some expressed concern that the indicated population would include patients at lower CV risk, where there was less evidence that the benefits outweighed the risks. There was also some belief that the choice of placebo may have slightly influenced the magnitude of the benefit of icosapent ethyl.
The agency is not obligated to follow its panels’ recommendation, but normally does so. The sNDA is under FDA priority review with a target date of December 28th.
ISS provided integrated support to Amarin Pharmaceuticals in preparation for this AdComm. ISS assisted in developing the AdComm strategy and guiding multiple mock AdComm rehearsal meetings. ISS support included:
- Identifying and recruiting consultants with statistical, cardiovascular, endocrine, and metabolic expertise to serve as speakers, mock panelists, and/or consultants
- Handling meeting logistics for company representatives, and consultants, and other
- Providing scientific support in developing the briefing book and presentation materials
- Managing the content creation and QC process with our proprietary DataTrove system
- Delivering reliable A/V support during the AdComm using the latest technology
ISS has almost two decades of experience in developing regulatory strategies including support for FDA Advisory Committee meetings. We are involved in more FDA AdComms per year than even the largest pharmaceutical companies. For more information on how ISS can help you prepare for your next meeting, contact email@example.com
DO YOU HAVE AN UPCOMING ADVISORY COMMITTEE MEETING?
Do you have an FDA Advisory Committee meeting, or another FDA meeting at the White Oak campus, scheduled?