This article presumes that the reader is familiar with the general situation of Amarin Corporation (AMRN) and its drug Vascepa ahead of the ANCHOR advisory committee meeting and PDUFA goal date. We've linked to supplementary content for readers unfamiliar with the company and its situation.
Amarin Regains Ahead of Vital Q4 Catalysts - 10/13/2013 (link)
Amarin: Explosive Volatility Expected from ANCHOR Catalysts- 9/13/2013 (link)
The biotech investment community is currently focused on the upcoming advisory committee meeting for the sNDA submitted for the drug Vascepa (icosapent ethyl) as a treatment for patients with TG >200 mg/dL and <500 mg/dL with mixed dyslipidemia. The drug will be indicated as an adjunct to diet for patients on statin therapy, as was the case for the MARINE NDA, although the controversy is centered around the "mixed dyslipidemia" portion of the label due to efficacy concerns that will later be defined by the REDUCE-IT trial. Here is an excerpt from the confirmed sNDA submission (link):
"BEDMINSTER, N.J. and DUBLIN, Ireland, April 23, 2013 (GLOBE NEWSWIRE) -- Amarin Corporation plc , a biopharmaceutical company focused on the commercialization and development of therapeutics to improve cardiovascular health, announced today that the Food and Drug Administration (FDA) has accepted its Supplemental New Drug Application (SNDA) seeking approval for the marketing and sale of Vascepa(R) (icosapent ethyl) capsules for use as an adjunct to diet in the treatment of adult patients with high triglycerides (TG ≥200 mg/dL and < 500 mg/dL) with mixed dyslipidemia."
Last Friday, the FDA released the briefing documents related to the scheduled advisory committee meeting for Amarin (link). While traders were initially excited by the reiterated positive data from the ANCHOR trial, the focus quickly shifted to certain negative comments in the documents that threatened the approvability of Vascepa in the ANCHOR indication due to concerns over its efficacy in cholesterol reduction. The emphasis was not on the ability for Vascepa to lower triglycerides, and the FDA reviewer was clearly indicating that the triglyceride-lowering portion of the ANCHOR label was approvable.
The ANCHOR trial measured patients over a 12 week period at two doses, although the most important data is from the 4 g/day treatment arm. This was the first table presented in the briefing documents:
Aggregated and reviewed by the FDA, this represents the data that will be interpreted by the 10 voting members of the advisory committee.
There has also been some concern about the placebo arm, which saw sharp increases in certain cholesterol and triglyceride levels by the end of the trial. This has led to ongoing suspicion about the paraffin (mineral oil) placebo that was used in the trial and potential interference with statin absorption, although it's worth noting that similar spikes in TG were seen in the late stage trials for Lovaza. Note that in those trials, GlaxoSmithKline (NYSE:GSK) did not use mineral oil. The placebo was also approved by the FDA during the design phase.
This point, among others, was discussed in an interview I had last year with Omthera Pharmaceuticals' CEO Jerry Wisler. (link) Note that Omthera was acquired by AstraZeneca on July 18, 2013 for $443 MM.
When taken out of context, some of the commentary made in the briefing documents about the sNDA and cardiovascular risk can be misleading. Amarin is conducting a study known as REDUCE-IT to establish a statistically significant improvement in cardiovascular risk for patients on both Vascepa and statin therapy versus statin therapy alone. The commentator suggests that the 12-week ANCHOR trial was not sufficient to fully establish a much sought-after correlation between secondary lipid targets (HDL-C, TG, etc.) and LDL cholesterol ("bad cholesterol"), which is a more direct biomarker that has a proven correlation to cardiovascular risk. While the benefit hasn't been fully established, the ANCHOR trial does provide limited efficacy data to support Vascepa.
It's also worth noting that ANCHOR was performed under special protocol assessment (SPA), which established a primary endpoint based on serum triglyceride levels and a non-inferiority test for LDL cholesterol between Vascepa and the placebo arm. This also allowed Amarin to claim that Vascepa does not increase LDL cholesterol like Lovaza, which has helped Vascepa take market share from Lovaza this year.
Also, the ANCHOR indication will not allow Vascepa to be prescribed for use in patients that do not fulfill the >200 mg/dL to 500 mg/dL triglyceride parameter. Since there is a well-established benefit in this patient population, which does not have an omega-3 prescription option, we believe that Vascepa is more likely to receive a positive vote than a negative vote based on risk/reward analysis. While Vascepa's cholesterol data isn't perfect, REDUCE-IT has now enrolled 6,000 patients and will provide the full data in 2016. Vascepa is also risk-free, and has been on the market for nine months.
The market seems quite evenly divided, and most are expecting a mixed vote that could make prediction of the final FDA decision difficult.
The following is a final breakdown between the pros, cons, and points to consider ahead of the ANCHOR advisory committee meeting:
-Drug has been on the market for 9 months, proven efficacy and safety in the real world from MARINE
-Enormous unmet need in this patient population after statin therapy, even for just TG reduction
-Apparently reduces LDL-C, does not increase it like Lovaza
-The FDA is clearly not concerned about the risk profile of Vascepa. The only serious adverse event was a fatal myocardial infarction in the placebo arm. There were no notable increases in any unfavorable biomarkers in Vascepa patients.
-REDUCE-IT has 6,000 patients
-ANCHOR performed under SPA
-ANCHOR was a 12-week study, and was not long enough to establish Vascepa as a treatment for cardiovascular risk
-Increases in lipid parameters in the ANCHOR placebo remain enigmatic
-The market had a clear negative reaction to the briefing documents, suggesting more confidence in a negative vote than before
Note that the meeting is scheduled for Wednesday, October 16th between 8:00 AM to 5:00 PM. It is likely that trading in AMRN will be halted by NASDAQ when the vote becomes public. Expect a continuation of the stocks' volatility.