This morning, the FDA released briefing documents that will be used as guidance by the panel members of the advisory committee (ADCOM) for Amarin’s Vascepa this Thursday. The package contains background info prepared by the FDA, highlighting key topics, conclusions and recommendations for Thursday’s meeting.
Generally, the briefing document findings were positive and supportive of Amarin’s REDUCE-IT Phase 3 study. This was a big hurdle for Amarin to get over, although the panel members could choose to go against the conclusions and recommendations of the briefing document.
Below are the 3 main topics of discussion and the FDA’s findings.
- Impact of Mineral Oil As Placebo Arm
Many questioned whether Amarin’s mineral oil placebo might be interfering with the background statin therapy and if placebo made Vascepa’s benefit appear larger than it really is. The FDA’s analysis concluded that there was no evidence of this:
- Managing Unexpected Safety Findings
Overall safety findings in REDUCE-IT were generally consistent with Amarin’s expectations, with the exception of two safety signals that emerged: (1) atrial fibrillation or atrial flutter events (heart rate increase) and (2) bleeding events.
More patients treated with Vascepa than placebo (3.1% versus 2.1%) experienced an adjudicated event of atrial fibrillation or atrial flutter requiring hospitalization. Additionally, more patients in Vascepa arm (11.8%) experienced a bleeding event compared to patients in the placebo arm (9.9%).
The ADCOM members will have to take these two safety findings into consideration, but we do not think it will make a significant difference to the decision making.
Generally, an increase in heart rate leads to higher risk of stroke events. However, in REDUCE-IT there was a minimal apparent effect on stroke, as stroke events were lower in Vascepa’s arm vs placebo.
The benefits of reduced cardiovascular events outweigh the adverse events in this case.
- Label: Patient Population
Amarin is seeking label expansion in adult patients with elevated triglyceride levels (TG >135 mg/dL). However, REDUCE-IT trial inclusion criteria and data do not support such a broad population. In our view, this will be the biggest challenge for Amarin come Thursday’s meeting.
REDUCE-IT population represented a higher risk group that the proposed indicated population. Most patients in the trial had baseline TG 200 mg/dL or greater. Approximately 72% were 175 mg/dL or greater, significantly higher than the proposed label of 135 mg/dL.
The briefing document stated:
Getting the 135 mg/dL label might be a stretch for Amarin. We think FDA might come back with a label in the 180-200 mg/dL level.
Bottom Line: Although there has been a lot of noise surrounding Amarin, the briefing document was generally positive. Mineral oil placebo did not seem to cause major concerns and the new safety findings do not outweigh the benefits. The company might have to give in a little on label, but Vascepa is still positioned as a multi-billion dollar drug. Amarin is well positioned heading into Thursday’s ADCOM.
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