After nearly a year of uncertainty, Amarin announced its commitment to complete REDUCE-IT (Reduction of Cardiovascular Events with EPA - Intervention Trial). The trial is designed to test the effects on cardiovascular outcomes of Vascepa, the company's high EPA omega-3 prescription fish oil product, in people with moderately elevated triglyceride levels between 200-499 mg/dL.
Last year the company said it might discontinue support of the trial, which began in 2011, after the FDA turned down the company's application for an expanded indication for Vascepa. Currently Vascepa is only approved for use in the small population of people with triglyceride levels of 500 mg/dL or over. The company had been counting on a greatly expanded indication in people with triglyceride levels between 200-499 mg/dL but the FDA reversed course when other triglyceride-lowering trials failed to show a benefit.
REDUCE-IT has now enrolled more than 7,000 patients. Amarin anticipates that enrollment will end in 2015 and that the trial will be completed in 2017 and the results reported in 2018. Results-- good or bad-- could be released earlier following a prespecified interim analysis by the independent data monitoring committee after 60% of the targeted events have occurred. The company expects that analysis to take place in 2016.
In its statements last year the company said it wasn't sure it would be able to finance the completion of the trial without revenue from the expanded indication. Amarin now says that it is confident it "can continue to improve operational cash flow while it completes the REDUCE-IT study." The company elaborated:
The cost run rate for the study is expected to decline modestly after enrollment completion, though it is expected to remain variable from period to period. Even before completion of patient enrollment, Amarin’s cash burn rate has been improving. Amarin anticipates that growing revenues from Vascepa sales will increasingly fund REDUCE-IT costs. Amarin also believes that it can continue to improve operational cash flow while it completes the REDUCE-IT study. These beliefs, together with Amarin’s perspective that the REDUCE-IT study is positioned to succeed and the large size of the potential opportunity, strongly align with the decision to continue the REDUCE-IT study with Amarin’s goal to increase shareholder value.
Amarin noted that the announcement of its commitment to finish REDUCE-IT follows the FDA's third denial of Amarin's appeal to reinstate a previous agreement-- a special protocol assessment (SPA) agreement-- which would have allowed the expanded Vascepa indication prior to the completion of REDUCE-IT.
When Amarin first stated it was contemplating stopping REDUCE-IT, Forbes reporter Matt Herper wrote an impassioned post about why he thought this would be a huge mistake. Here is some of what he had to say:
Stopping REDUCE-IT, which could be the first study to show that a fish oil pill is worth taking, would be considered unethical by many of the doctors who conduct clinical trials and whose endorsement the company needs. It could create bad press that would make Vascepa even harder to sell, be seen as a vote of no confidence by Amarin in its own drug, and remove a huge potential upside for Vascepa sales. In short, it would be both wrong and commercially stupid.
...
... the idea is that there is a contract between Amarin and patients, not between Amarin and the FDA. At the very least, stopping the study is likely to weaken Amarin’s commercial case in the meantime. The company really has no choice but to dig in its heels and wait for the REDUCE-IT results in three years.
The trial's principal investigator, Deepak Bhatt, of Brigham and Women's Hospital in Boston, sent the following comment:
One of the major questions in medicine is whether triglyceride lowering decreases cardiovascular event rates. Large amounts of data show that triglycerides are a risk marker, but we need to determine if triglyceride elevation is a modifiable risk factor. REDUCE-IT provides a great opportunity to answer this question definitively - and positive or negative, it will substantially advance our knowledge of risk reduction. I was very pleased to see that the company funding the trial has reaffirmed their commitment to completing the study; it is the right thing to do scientifically as well as morally, as there really is an obligation to the enrolled patient to see a trial through.
