Investors will have to wait until November to find out the details of Amarin Corp. plc's cardiovascular (CV) outcomes trial with Vascepa, but Wall Street heard enough Monday to increase the share value of the Dublin-based company by 315 percent, or $9.41, closing at $12.40.

The news could create a spike in demand for which Amarin is ready. CEO John Thero noted that the company provided guidance at the start of the year that the firm would "spend somewhere around $10 million to add a bolus of inventory beyond what we would be purchasing in the ordinary course [of events, in order] to support what could be a rapid uptake following Reduce-It results. We also had a talk about the work that we have done with our suppliers to increase their capacity, such that we believe that for next year, they'll be in a position to be able to provide us supply that would be able to support well in excess of $1 billion in revenues."

Approved in the summer of 2012, Vascepa is an ethyl ester of eicosapentaenoic acid (EPA) given as an adjunct to diet to cut back triglyceride (TG) levels in adult patients with severe hypertriglyceridemia. The global study called Reduce-It in 8,179 statin-treated adults with elevated CV risk met its primary endpoint, yielding a 25 percent lower risk of major adverse CV events (MACE) in the intent-to-treat patient population to a high degree of statistical significance (p<0.001).

Enrollees in Reduce-It signed up with low-density lipoprotein cholesterol (LDL-C) levels between 41 mg/dL and 100 mg/dL (median baseline LDL-C 75 mg/dL) controlled by statin therapy and various CV risk factors, including persistent elevated TGs between 150 mg/dL and 499 mg/dL (median baseline 216 mg/dL) and either established CV disease (the secondary prevention cohort) or diabetes mellitus and at least one other CV risk factor (the primary prevention cohort).

The 25 percent MACE drop was "supported by robust demonstrations of efficacy across multiple secondary endpoints," Amarin said, and the finer points will roll out in Chicago at the American Heart Association (AHA) scientific sessions. "What the medical community is looking for is consistency of magnitude of effect," said Chief Medical Officer Craig Granowitz during a conference call with investors.

And that's what the company aims to provide. CEO Thero said that the earlier Japan Eicosapentaenoic Acid Lipid Intervention Study, or JELIS, "had this hypothesis [that] EPA is different" from other omega-3 fish oil-based products that have failed. The 18,000-participant JELIS trial, completed in 2004, was sponsored by Kobe University in Kobe, Japan, with collaborator Mochida Pharmaceutical Co. Ltd., of Otawara, Japan. Specifically, EPA doesn't raise LDL, lowers apolipoprotein B and knocks down biomarkers of inflammation. EPA "has broad effects, and I think [Reduce-It] was essentially the follow-on to an already successful study in Japan. Translating that now on a global basis, I think, will be an interesting question. It probably will spur considerable development in research by folks in various areas to try to figure out what's the proportion of the benefit that is driven by endothelial cell function vs. inflammation vs. plaque regression, etc."

Label expansion bid planned

Reduce-It took almost five years to finish. "Four to five years was a target for us," Thero said, consistent with statin trials. "We are talking about MACE components that range from the softer MACE – important but softer MACE of hospitalization for angina and revascularization, [which is] very expensive of course – to the harder MACE of nonfatal death, nonfatal stroke and CV death. And there'll be commentary on, I suspect, all of those" at the AHA meeting, he said.

On the subject of pricing, "we draw a parallel here in trying to create or forge a new market [similar] to that which was done with statin therapy. We're out to try to help millions, hopefully tens of millions of patients. And to do that, we need to ensure that the therapy is affordable. [Vascepa is] priced at a level today essentially on parity with a generic earlier-generation product, despite the fact that an earlier-generation product has failed in outcome studies. And while that will cause us to take another look at pricing, we really think this is more of a volume play than it is a pricing play."

An old-timer in the space, Lovaza (omega-3-acid ethyl esters, Glaxosmithkline plc) is available in generic form. London-based Astrazeneca plc is conducting a CV outcomes study with Epanova (omega-3-carboxylic acids).

Jefferies analyst Roger Song pointed out that the magnitude of MACE drop won by Vascepa "is so far the greatest among all therapies on top of statins, far exceeding the clinically meaningful CV benefit expectation." In their CV outcomes trials, two PCSK9 inhibitors (Repatha [evolocumab, Amgen Inc.] and Praluent [alirocumab, Sanofi SA/Regeneron Pharmaceuticals Inc.]), reduced MACE risks by 15 percent. So did Ilaris (canakinumab), the monoclonal antibody targeting interleukin-1 beta from Basel, Switzerland-based Novartis AG. "Our doctor survey suggested 10-15 percent-plus risk reduction in MACE is considered clinically meaningful," Song wrote in a report, which puts Vascepa well into the black.

During the fourth quarter of this year, Amarin will begin hiring about 250 more sales reps to supplement about 150 on board now, and they will target more than 40,000 physicians as compared with about 20,000 today. The company plans to submit a supplemental NDA to expand Vascepa's label into the mixed dyslipidemia population in early 2019. Data from more subgroups will be reported next year, too.