Amarin (NASDAQ:AMRN) faces the firing squad tomorrow when the Food and Drug Administration's advisory committee reviews its lipid-lowering drug Vascepa. The drug is already approved for patients with extremely high triglyceride levels, but Amarin asked the FDA to expand its approval to include patients with moderately high triglyceride levels.
Here are three things investors need to watch at the meeting tomorrow:
Issues with placebo
The FDA briefing documents highlight the increase in triglycerides in the placebo group and point out that it could have been caused by the mineral oil that was used as a placebo. While certainly possible, it doesn't seem like a major issue since the group taking Vascepa saw their triglyceride levels decrease substantially.
Triglyceride levels also increased in the patients taking placebo in the trial used to support its current approval, so it looks to me like the FDA is just highlighting the issue because the agency's job is to nitpick about every little issue, but it isn't a major point of contention for the FDA. If the agency was really concerned, it would have had a specific question about the appropriateness of using mineral oil in the questions that the doctors will discuss and vote on at the end of the meeting.
Of course, panels have a way of taking on a life of their own. If one outspoken panel member thinks it's a major issue, the panel could end up spending much more time on the issue than it really deserves.
Approval before REDUCE-IT?
That's the billion-dollar question. GlaxoSmithKline's (NYSE:GSK) competing fish oil, Lovaza, is on pace to sell about $1 billion this year, and it's not hard to see how Amarin could reach or exceed that level if Vascepa is approved for moderately high triglyceride levels. GlaxoSmithKline gathers much of its sales from off-label use of Lovaza, which isn't approved for the moderately high triglyceride indication, either, so having the indication on the label would make it easy for Amarin to compete with GlaxoSmithKline.
Amarin set up a special protocol assessment, or SPA, with the agency, agreeing that the FDA would approve the drug if the clinical trial for the moderately high triglyceride levels was positive (it was) and that the company substantially enrolled a clinical trial, dubbed REDUCE-IT, that measures clinical outcomes (it has).
So, if Amarin has held up its half of the deal, why are we having an advisory panel to review the approval? SPAs always come with a catch; the FDA has the right to change its mind if circumstances change. In this case, the FDA lays out the issue very clearly in the briefing documents, "Recent clinical trials and meta-analyses have failed to confirm definitive cardiovascular benefit with EPA and DHA supplementation, however."
The FDA, patients, and doctors don't care about triglyceride levels, which are just laboratory tests; they want to reduce heart attacks and strokes, but it's not clear that EPA and DHA, which are fish oils, reduce cardiovascular events.
That's the purpose of the ongoing REDUCE-IT trial, but with the cardiovascular landscape a little more cloudy than it was when the SPA was agreed to in 2009, the FDA is questioning whether to approve the expanded indication now or wait for the outcomes data in a few years.
The FDA is probably feeling pretty smug after having required Merck (NYSE:MRK) to run an outcomes study for Cordaptive, which lowered bad cholesterol, increased the good kind, and lowered lipid levels, but failed to reduce cardiovascular events such as heart attacks and strokes. The FDA's counterparts in Europe approved the drug without the data, and Merck had to withdraw the drug from the market.
The FDA is going to argue that there isn't much harm in waiting. Amarin will point out that waiting a few years will cause patients to have high triglyceride levels that will cause more heart attacks and strokes (assuming that REDUCE-IT really shows that Vascepa can reduce them).
We'll have to wait until tomorrow to see what the panel of outside experts thinks, but it's clear the REDUCE-IT trial will be the main sticking point.
The comments, not the vote
If the committee recommends not approving the expanded indication until the REDUCE-IT data is available, you can turn off the webcast; there's no way the FDA will go against their recommendation.
If the committee votes to recommend approval without the REDUCE-IT data, listen closely to the committee members' reasons for why they voted the way they did. It'll give you a good indication if the FDA will follow the recommendation.
The situation reminds me a lot of Orexigen's (NASDAQ:OREX) panel reviewing its obesity drug Contrave. The advisory committee recommended approving Contrave without a safety trial, but if you listened to the panel members carefully, many said they would have liked to see a pre-approval trial but that it didn't seem fair for the FDA to move the goalposts. The FDA doesn't care about being fair, and Orexigen was asked to run a new clinical trial.
If the panel members make similar arguments about the SPA tomorrow, you can ignore their vote. The only way the FDA approves the expanded indication is if the committee convinces the agency that there's a good chance that lowered triglyceride levels translates into clinical outcomes.
Check back to Fool.com after the committee when we'll break down the vote.