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As fateful FDA review nears, Amarin makes case for Vascepa

Amarin CEO John Thero said Tuesday he expects an expert Food and Drug Administration panel to challenge the company with “intentionally tough” questions on clinical data supporting the company’s request for an expanded approval of its fish oil-based drug Vascepa. On Nov. 14, an FDA advisory committee will consider Amarin’s application to broaden Vascepa’s label to include cardiovascular risk reduction. A “naturally adversarial tone” from these expert panels is standard, Thero said, adding that Amarin has prepared for the test, even holding mock meetings to simulate the expected debates.The company’s chief executive previewed those anticipated arguments on a Tuesday call discussing third quarter results. At the end of October, the company received an advanced draft of the FDA’s briefing documents on Vascepa, which outlined the agency’s focus areas for the panel discussion. An FDA approval decision is expected by Dec. 28.

Next Thursday’s advisory committee meeting is preceded by more than a year of build-up since Amarin first released clinical results from a cardiovascular outcomes study of Vascepa (icosapent ethyl). That data vaulted the company from a small industry player selling a fish oil-based pill to a $6 billion biopharma with a heart treatment predicted to earn billions of dollars.

That clinical trial, called REDUCE-IT, will be the center of attention for the panel. The primary result of a 25% relative cardiovascular risk reduction has already led Vascepa sales to skyrocket, likely through off-label use. The drug brought in $112 million for the three months of July, August and September — up 103% from the same period a year ago.

On the Tuesday call and in simultaneous regulatory filings, Amarin outlined the primary topics it expects to be debated.

Most of those are typical clinical considerations on a drug’s benefits and risks, as well as related points on what patient population an approved label would include.

Amarin expects the committee to dissect the data by different patient populations and subgroups. The company also foresees discussion on safety data that showed patients taking Vascepa had higher rates of atrial fibrillation or atrial flutter leading to hospitalization (3.1% versus 2.1% on placebo) and adverse events of bleeding (11.8% versus 9.9% on placebo).

And Amarin also acknowledged the likelihood it will face questions on the use of a mineral oil placebo, a choice that has stirred controversy and debate in investor and medical circles since the release of REDUCE-IT data.

The REDUCE-IT placebo group received mineral oil pills, which were chosen to mimic Vascepa’s color and consistency. The theory goes that mineral oil could have affected statin absorption, worsening the placebo group and contributing to the statistical difference between the two groups.

The primary piece of evidence underlying the theory is median changes to baseline LDL cholesterol levels. While patients on Vascepa saw bad cholesterol rise by 3.1% on average, placebo patients saw a mean LDL increase of 10.2%.

In the months leading up to the advisory committee, Amarin has defended its use of mineral oil, pointing to special protocol agreements with the FDA that allowed it as an acceptable placebo.

“We do not believe such an interaction occurred,” Thero said on the Tuesday call, adding that even if determined a plausible theory, it’s “unlikely to change the overall conclusion of treatment benefit.”

The FDA also requested quarterly, unblinded safety analyses by REDUCE-IT’s independent data monitoring committee to search for evidence of biological activity from the placebo, Amarin stated. That committee never found such evidence and consistently recommended continuing the study.

Amarin has detailed its thoughts on the mineral oil question in an official response exceeding 2,500 words, which could preview how Amarin plans to handle the topic next Thursday. The biopharma points to an analysis of individual patients that showed a mix of increasing, decreasing and flat LDL levels in both the placebo and Vascepa groups.

“If mineral oil affected statin absorption significantly, it is reasonable to expect that such an effect might be evident in all patients on placebo … rather than the observed mixed results that include many patients with LDL-C decreases or lack of change in LDL-C,” the document states.

Final versions of the FDA’s briefing documents are expected next Tuesday, two days before the meeting. If the label expansion is approved, Amarin intends to double its salesforce from 400 to 800 employees.

As is typical for the day-long affair of advisory committees, Amarin plans to ask the Nasdaq to halt market trading next Thursday.