- Amarin's chances of securing a broader approval for its heart pill Vascepa look stronger after Food and Drug Administration documents posted Tuesday show the agency to hold a favorable view on a key controversy surrounding the biotech's supporting study evidence.
- On Thursday, an expert panel of FDA advisors will review Amarin's case for dramatically expanding Vascepa's approval to include cardio-protective use in patients at risk of heart disease, a label that would cover millions of Americans and potentially be worth billions of dollars for Amarin.
- The advisory committee meeting will be the final step in a review process expected to conclude with an FDA decision this December. Results from Amarin's REDUCE-IT study, published early this year, showed treatment with Vascepa led to a dramatic 25% reduction in heart risks compared to placebo, but questions have lingered over whether use of a mineral oil placebo inflated the drug's reported benefit.
The documents, written by FDA staff for presentation at Thursday's meeting, appeared to ease investors concerns the agency might weigh in negatively on Amarin's application for Vascepa (icosapent ethyl). Shares in the biotech rose by 20%, pushing the stock near highs reached earlier this year.
Discussion at the meeting will likely center on three questions spurred by the results of REDUCE-IT, a nearly five-year study that enrolled more than 8,000 patients at high risk of cardiovascular disease and who were already on statin therapy.
The observed 25% risk reduction for Vascepa versus placebo was surprisingly high, and argues for the pill's place as mainstay heart therapy alongside statins. Some wondered, however, whether using a mineral oil placebo led to the higher LDL cholesterol levels seen among patients in the control group. Higher LDL, or "bad," cholesterol numbers are a known heart risk factor.
The working hypothesis was that the placebo could have inadvertently reduced absorption of statins, thereby allowing LDL levels to climb and flattering the benefit versus Vascepa.
FDA tests, however, weren't able to conclusively prove that hypothesis, the documents show, and in either case the impact of the raised LDL levels would not have been sufficient to substantially change REDUCE-IT's results.
"The median increase of 10-13% LDL-C from baseline observed in the trial would increase cardiovascular risk by approximately 3%," FDA staff wrote in the briefing documents. "This small increase of risk appears numerically small and is unlikely to change the overall treatment effect direction."
FDA staff also appear open to a broad label for Vascepa, directing panel experts to consider labeling language that would go beyond just patients with established heart disease.
Another topic that could emerge as a point of discussion Thursday is Vascepa's safety. REDUCE-IT showed that patients on Vascepa experienced higher rates of atrial fibrillation and bleeding than those given placebo — a notable signal as neither risk was seen to be comparatively more pronounced in earlier studies.
Still, on the whole, FDA staff appear to be generally supportive of Amarin's case.
"The questions look pretty broad and we think investor fears of potential issues with study design (i.e. mineral placebo) or safety should be alleviated given the tone of the documents," wrote Stifel analyst Derek Archila in a Nov. 12 note to investors.
Vascepa, an omega-3 fatty acid product that contains purified EPA from fish oil, is already approved to treat elevated triglyceride levels. If the FDA expands that to include cardiovascular risk reduction, Amarin would be able to market the drug to a dramatically wider market.
Since Amarin first released REDUCE-IT data, sales of Vascepa have steadily increased, suggesting that some doctors are already prescribing the drug off-label.