Tuesday, September 25, 2018

Amarin fish oil capsule shows dramatic benefit for cardiovascular patients, potentially upending market


SEPTEMBER 24, 2018
The biopharma company Amarin is making some heart-medicine history Monday with its proprietary, prescription formulation of fish oil, called Vascepa.
In a stunning clinical trial result that upends years of skepticism about the long-term heart benefit of products containing omega-3 fatty acids, Amarin’s Vascepa significantly reduced the risk of deaths, heart attacks, strokes, and other serious cardiovascular events compared to a placebo.
Amarin designed its cardiovascular outcomes study, known as REDUCE-IT, hoping to show Vascepa could meet the primary endpoint with a 15 percent risk reduction.
The result announced Monday: a 25 percent risk reduction — highly statistically significant.
“This is absolutely the most significant study in the field of cardiovascular risk reduction since the statins were introduced,” said Dr. Matthew Budoff, a cardiologist at UCLA and a Vascepa study investigator.
Statins became commercial blockbusters generating billions of dollars in sales because large clinical trials proved a positive link between cholesterol lowering and the prevention of fatal heart attacks and strokes. The newer class of injectable cholesterol-lowering medicines known as PCSK9 inhibitors from Amgen, Regeneron Pharma, and Sanofi reduce cardiovascular risk by 15 percent.
With a greater 25 percent reduction risk for patients, Vascepa could be the next cardiovascular blockbuster therapy, potentially prescribed to millions of Americans.
Amarin shares closed Friday at $2.99. As dawn broke Monday, Amarin’s stock price surged to $10, a 200 percent-plus move higher in the pre-market trading session.
Vascepa was approved by the Food and Drug Administration in 2012 to treat people with high levels of triglycerides, a type of fat found in blood. But the product’s commercial output has been modest to date — sales last year totaled $181 million — because there was no scientific proof linking triglyceride lowering to improved cardiovascular outcomes.
All previous outcomes studies investigating different formulations of omega-3-containing products have been unsuccessful, leading to heavy skepticism in the cardiology community about the medicinal value of these supplements. As recently as August, a 15,000-patient study of a different prescription-grade fish oil called Lovaza failed to detect any improvement in heart benefits.
“I thought the Vascepa study would be negative, colored by all the prior failed studies so I’m surprised. I’m willing to eat my shoe on this one. This could be really beneficial to people,” said Dr. Ethan Weiss, a cardiologist at the University of California, San Francisco Medical Center. Weiss was not involved in the Amarin study.
“I need to see the [detailed] data, but if these are the results, then this may be a game changer,” said Dr. Martha Gulati, chief of cardiology at the University of Arizona College of Medicine. Gulati was not involved in the Amarin study.
Amarin used a press release Monday morning to disclose the top-line results from the Vascepa REDUCE-IT study. More detailed data are being presented at the American Heart Association annual meeting on Nov. 10.
Amarin has long insisted that the special characteristics of Vascepa would prove superior to other fish oil formulations. Vascepa contains only highly purified EPA, the most beneficial omega-3 fatty acid. Other fish oil pills, including Lovaza, contain a mix of EPA and DHA, the latter of which is known to raise levels of bad cholesterol. Vascepa is given at a higher 4-gram daily dose compared to competitors.
The company designed the REDUCE-IT study to maximize Vascepa’s benefit. The 8,179 patients entered the study with cholesterol levels that were controlled by statin therapy but they also had other heart-related ailments, including persistently high triglyceride levels or diabetes, that placed them at greater risk.
The patients were randomized to treatment with Vascepa or a placebo pill and followed for a median of nearly five years. The results:
Vascepa demonstrated an approximately 25 percent relative risk reduction in the primary endpoint, which measured first occurrence of cardiovascular death, non-fatal heart attack, non-fatal stroke, coronary revascularization, or unstable angina requiring hospitalization, Amarin said.
On safety, Vascepa was well-tolerated with a side effect profile consistent with the drug’s currently approval label, the company said.
“We are delighted with these top-line study results,” Amarin CEO John Thero said in a statement. “Given Vascepa is affordably priced, orally administered and has a favorable safety profile, REDUCE-IT results could lead to a new paradigm in treatment to further reduce the significant cardiovascular risk that remains in millions of patients with LDL-C controlled by statin therapy, as studied in REDUCE-IT.”
The 25 percent risk-reduction headline number is significant, but Weiss, the UCSF cardiologist, said he’s holding off on hailing the finding as the most significant until details from the study data are aired publicly in November. He has questions: What factors, exactly, drove the risk reduction? How much triglyceride lowering was observed? How narrow was the enrolled patient population?
But if the data hold up, Vascepa could become a very big drug. At an annual price of around $2,400, Vascepa is already broadly covered by insurance companies. Even if Amarin raises the drug price to reflect the REDUCE-IT results, it will still likely be a relative bargain compared to other heart medicines. PCSK9 inhibitors cost about $14,000 annually and insurers have tried to restrict their use.
Amarin has already been involved in litigation against generic drug makers seeking to bring cheaper versions of Vascepa to the market. The company’s patents on the drug expire in 2030, although the results of the REDUCE-IT study, bolstered by additional FDA approvals, could offer more intellectual property protections.
Amarin also believes the cardiovascular benefit seen in REDUCE-IT is due to Vascepa’s purity and dose and cannot be replicated by other prescription-grade or over-the-counter fish oil products. Whether that proves to be true, or not, will depend on the results of competing clinical trials. AstraZeneca is conducting an outcomes study of its prescription-grade fish oil product called Epanova, also utilizing a higher dose, like Vascepa. A readout from that study, dubbed STRENGTH, could come next year.
“I went into this study not convinced that Vascepa would make a difference, but these results will definitely change my practice and the way I treat patients,” said Dr. Norman Lepor, a cardiologist at Cedars-Sinai Medical Center in Los Angeles. Lepor enrolled patients in the Vascepa study.

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