New evidence emerges from Amarin’s EPA drug trial; company to appeal ruling invalidating patent

On the science front, a new evaluation of the data from Amarin’s REDUCE-IT trial of its drug Vascepa, which is a highly concentrated ethyl ester form of EPA, was presented at a recent American College of Cardiology.  Researchers combed through the data from the trial and came up with some interesting findings about what endpoints are important when looking at EPA’s effects on cardiovascular health.

For REDUCE-IT Amarin enrolled 8,179 patients at 473 sites in 11 countries.  The subjects had elevated cardiovascular risk and were already being treated with statins. The trial found that taking a daily 4 gram dose of EPA cut the combined rate of first and subsequent nonfatal heart attacks, strokes, cardiovascular deaths, procedures for coronary artery disease such as stenting, or hospitalizations for unstable angina by 25% and 30%, respectively, over a median of 4.9 years of follow-up. 

In addition to statins, most patients in the trial were already on antiplatelet therapy, ACE-inhibitors/ARBs, beta blockers and aspirin. That led the Amarin research team to conclude that its drug, the form of which the company refers to as icosapent ethyl, offered a separate and incremental benefit.

The most recent look at the Amarin data, the results of which were presented at the meeting, delved into how a high dose EPA might be showing these benefits.  As EPA has previously been shown to help lower high triglyceride levels, the assumption was that this was the key factor.  The lower the triglycerides, the fewer the cardiac events, in other words.

The higher EPA levels, not lower triglycerides, found to be key factor

But that’s not what the most recent research found.  The researchers found a direct correlation higher blood levels of omega-3s (in this case the specific level of EPA was of interest) and fewer cardiac events.  Triglyceride levels, whether lower or higher, were not correlated in the same way.

According to an American College of Cardiology report on the meeting, the study’s lead author, Dr Deepak L. Bhatt, MD, of Brigham and Women’s Hospital and Harvard Medical School, had this to say about the research:  "A major missing piece of the puzzle, and what many clinicians want to know, is how icosapent ethyl actually works to produce such dramatic cardiovascular risk lowering. On-treatment EPA levels achieved via the drug strongly correlated with lower rates of cardiovascular events, heart attack, stroke, coronary revascularization procedures, unstable angina, sudden cardiac arrest, new heart failure, or death for any reason.”​

“Changes in triglycerides levels and other cardiovascular risk markers, including LDL, HDL, apoB and CRP, appear to be responsible for a significantly lesser portion of the overall observed benefit," Bhatt added.​

Expert: Finding bolsters argument for supplements

Leading omega-3s researcher William S. Harris, PhD, professor at the Sanford School of Medicine at the University of South Dakota, said the finding could provide a significant boost to the argument in favor of omega-3 supplements.  Harris is also CEO of OmegaQuant, a company that offers a simple test for measuring blood levels of omega-3s.

“The important thing here is whether you’re talking about Vascepa or Lovaza (a previously approved drug derived from fish oil), because they were lowering triglycerides an inattentive doctor might have assumed that’s how they worked and that was what was important,​” Harris said.

“Now we know that lowering the triglycerides was not correlated with lower cardiac event risk.  It was the EPA levels in the blood. You can achieve high omega-3s levels in the blood through diet, but it has also been shown you can achieve those with dietary supplements,”​ he added.

Great care would need to be exercised by omega-3 dietary supplement marketers in talking about the new results, though. In the past Amarin has sued supplement companies ​​that it alleged had too closely linked their products’ effects with the results of Amarin’s research.

Patent ruled invalid for being too ‘obvious’

On the patent front, a court in Nevada ruled that Amarin’s patent on its drug was invalid because a researcher or product developer could have come to the same conclusions as did the drug company when looking at the same references of so-called ‘prior art.’ The ruling came in an action concerning several drug companies seeking to make generic versions of Amarin’s drug.

“The asserted patent claims are all invalid as obvious,” ​the court ruled. 

Attorney Kevin Bell, a partner in the firm Arnall Golden Gregory LLP, who has represented natural products companies and others in patent actions, said this claim of a patent being obvious is a common tack in such cases.  It’s not clear whether the ruling will stand up under appeal, so he cautioned the marketplace not to assume the Nevada judgement has opened the door wide for EPA generic drugs.

“This is the most common defense asserted by defendants trying to invalidate patents.  It has been around for over 50 years and there is a significant amount of case law on 103 invalidity cases.  What everyone needs to know is that this fight is far from over.  Amarin will appeal this to the US Court of Appeals for the Federal Circuit, which is a specialized appellate court for patent cases.  Given the arguments made by the parties and the evidence presented, the Federal Circuit could reverse the district court’s ruling,”​ Bell said.

“Amarin strongly disagrees with the ruling and will vigorously pursue all available remedies, including an appeal of the Court’s decision and a preliminary injunction pending appeal,” ​said John F. Thero, president and chief executive officer of Amarin, in a statement on the investor relations portion of the company’s website​​.

Amarin still seeking to protect market share against dietary supplement encroachment

Amarin had previously sought to protect its market share for its drug by alleging that manufacturers of ethyl ester forms of EPA used in dietary supplements, including Dutch supplier DSM, were infringing on its patents.  The effort was seen as essentially arguing that offering an omega-3 supplement in the ethyl ester form, as opposed to others such as triglyceride or phospholipid forms, was tantamount to marketing an unapproved drug, and one that violated Amarin’s patent to boot. That effort seemed to have stalled when the US Supreme Court decided in December not to hear Amarin’s appeal​​ of an unfavorable ruling by the International Trade Commission.

Amarin, for its part, said it remains highly committed to the legal defense of it patents, whether the threats come from competitors in the drug realm or from dietary supplement companies.

“Amarin remains fully committed to defending the Vascepa franchise against any company that seeks to mislead the public and cardiovascular patients in need by fraudulently leveraging the landmark REDUCE-IT study results or the REDUCE-IT and Vascepa names as part of marketing their products,”​ the company said in a statement.