November 6th, 2013

Why Amarin Has To Finish Its Big Fish Oil Study

The following post is by Matt Herper, who covers science and medicine for Forbes magazine.

When a panel of experts appointed by the Food and Drug Administration said the agency should deny Amarin Pharmaceuticals a broader marketing approval for its fish oil pill Vascepa, the company’s shares tanked 60%, making it the worst-performing biotechnology stock on the Nasdaq or New York Stock Exchange last week. The company reacted with shock and many of its investors became angry.

One idea that came up almost immediately: Amarin should drop the big and expensive study it had started to prove that taking Vascepa to lower triglyceride levels really does prevent heart attacks, strokes, and surgical procedures. Stopping the trial, called REDUCE-IT, was one of the first ideas that analysts brought up on the conference call that followed Amarin’s rout at the FDA. And Joseph S. Zakrzewski, Amarin’s chief executive, refused to rule it out. “We’ve been planning and hopeful of a positive meeting today. But as I said earlier, we’re going to take a look from top to bottom and look at everything.”

I responded on Twitter.

After that, I spent a lot of time arguing with Amarin investors who thought that ending the study was a splendid idea – after all, it is costing Amarin, which has $270 million in the bank, $30 million to $40 million a year and will last until at least 2016, although costs will decrease with time. Amarin had expected REDUCE-IT to be funded by Vascepa sales, which may not come. Why not double down on expanding the sales force instead? Brian Orelli at The Motley Fool accused me of forgetting that a company’s primary duty is to its shareholders, not to science.

The investors and Orelli are not remembering their Pharma history. 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.

Why am I so confident? I remember when a big heart study run by a drug company was stopped for commercial reasons. It wound up being national news and being decried angrily in the Journal of the American Medical Association.

This was back in 2003, and the study was stopped by Pharmacia, when it was being run by Fred Hassan. The study, called CONVINCE, tested a blood pressure medicine called verapamil against standard blood pressure drugs. The study had recruited 16,600 patients, and was supposed to continue until patients had 2,246 heart attacks, strokes, or heart-related deaths.

Instead, Pharmacia stopped the trial two years early “for commercial reasons,” when there had been 729 heart attacks, strokes, or heart related deaths. The independent scientists running the study were told that the study was stopped for “business considerations.” In other words, even though the patients had volunteered, the company did not want to continue to fund the study.

That led to a stinging JAMA editorial calling the decision “a broken pact with researchers and patients.” The authors, Bruce Psaty and Drummond Rennie, include a long list of stopped studies, including a Bristol-Myers Squibb study of cancer drug Taxol, a Pfizer study of doxorubicin, also for cancer, and a Novartis study of fluvastatin, for high cholesterol.

But the JAMA authors argued that stopping studies for business reasons is wrong:

In a capitalist society, legal contracts permitting, companies can fire employees, decline to purchase components or equipment, and even cancel some consulting or research arrangements with scientists. But the recruitment and involvement of human research participants places clinical trials in a category decidedly distinct from the customary swapping and trading of ordinary goods and services. When patients or other research participants are recruited for scientific investigations, they agree willingly to expose themselves to risk. Individuals often participate out of a sense of altruism, and counted among the most important reasons for joining trials are the improvements in their own health, the contributions to science, and the improvement of the health of others.

They further argue that stopping trials early represents a violation of the Declaration of Helsinki, used as an ethical guide for medical experiments. It’s wrong to ask patients to enroll in a study that is too small to have a chance at delivering an answer. So isn’t it also wrong to shrink a study that was big enough by stopping it early?

There’s room for disagreement here; Psaty and Rennie cite other articles that argue it is perfectly ethical for companies to stop trials to deploy limited resources. But the anger many investors feel against the FDA doesn’t matter to those arguments; 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.

I reached out to a public relations person retained by Amarin about this story and did not receive a response.

 –Matt Herper

Reprinted with permission from Forbes.

Comments are closed.