Last month’s EU approval of Vazkepa – a treatment derived from fish oil and known as Vascepa in the US – added much-needed ammunition to the arsenal of doctors fighting cardiovascular disease. Still other similar treatments produce lukewarm results, and the possibility of approvals being withdrawn is in the air.
Icosapent Ethyl, a derivative of fish oil formulated by US-Irish biotechnology Amarin, was recently the first EU-approved treatment to reduce the risk of stroke and heart attack in patients with elevated triglycerides – a type of fat, previously treated with statins.
The approval is aimed at an urgent medical need. Cardiovascular disease (CVD) is the leading cause of death worldwide, according to the World Health Organization. There are over 60 million people in Europe with CVD and the cost to the economy is estimated at around EUR 210 billion per year.
Icosapent Ethyl is a purified form of EPA, one of the two main omega-3 fatty acids in fish oil, the other is called DHA. The drug, marketed in Europe under the name Vazkepa, was approved by the FDA in 2012 under the brand name Vascepa to lower blood triglycerides in people with hypertriglyceridemia. In 2019, the FDA expanded Vascepa’s indication to reduce the risk of stroke and heart attack in high-risk patients. This was the result of a phase III clinical study that showed that the risk of adverse cardiovascular events was reduced by 25%.
How exactly Vascepa had such a profound benefit in this study is still largely unclear. Another clinical study found statin-treated high triglyceride patients given Vascepa showed a significant 17% decrease in the build-up of low-attenuation plaque, a type of coronary plaque.
“The stabilization of the coronary plaques is an important finding with Vascepa and can partly explain the significant cardiovascular benefit that results from it [the previous phase III study]”Amarin CMO Craig Granowitz commented in a recent press release.
Amarin representatives did not respond to requests for further comment. The company, which posted record revenues in 2020, is currently in the midst of a CEO reshuffle and bitter patent litigation after a US court invalidated its patents on Vascepa last year and the drug faced competition from generics. As a result, high hopes rest on its performance in the EU market, where the company still holds patents.
Independent observers heralded the European Commission’s decision as a breakthrough for both fish oil products and cardiovascular treatments.
“Although we do not have an opinion on any particular product, we very much welcome the development of new therapies for CVD diseases,” said Birgit Beger, CEO of the European Heart Network. “Innovation in CVD in terms of new drugs or new therapies is very slow.”
Over a dozen CVD treatments have been approved by the EMA in the past five years, but the vast majority have been generic or biosimilar.
“The US development pipeline is stronger, clinical trials are relocating from Europe, and China has a rapidly growing stake in cardiovascular research and development,” added Beger.
“Europe as a whole still has competitive research outputs and capacities, supported by research networks, partnerships and European infrastructure, but it needs to make the translation of science into clinical solutions and products more effective.”
Fish oil-derived treatments have recently taken a roller coaster ride in both clinical trials and the business world. They have been viewed by scientists as a potential panacea for everything from CVD to brain disease to Covid-19. Yet they are often stuck in the no man’s land between supplements and drugs, a divide that has become complicated in recent years.
While the EMA is responsible for pharmaceuticals, food supplements are regulated separately by the European Food Safety Authority (EFSA). The two’s views on fish oils and heart disease have fluctuated over the years and “aren’t exactly the same,” said Clemens von Schacky, a German cardiologist and CEO of German commercial testing lab Omegametrix.
Approval of all drugs based on blends of EPA and DHA to reduce cardiovascular risk was withdrawn by the EMA in 2018 after the regulator concluded that there was insufficient evidence to demonstrate their benefits in this indication to be proven – although they are still approved for lowering triglycerides. Meanwhile, EFSA continues to claim that EPA and DHA contribute to normal cardiovascular function. These differences, along with reimbursement issues and generic competition, have affected companies’ business plans.
Part of the complexity of the problem may be that omega-3 treatments are most effective when there is a deficiency. However, deficiencies typically affect both EPA and DHA. This is also one reason why Vascepa’s remarkable success in clinical trials has raised some eyebrows in the scientific world.
“One problem with Vascepa is that it only contains one marine omega-3 fatty acid, EPA. Humans cannot synthesize the other important omega-3 fatty acid DHA from EPA and therefore need a direct supply of DHA for building and maintaining the brain and a variety of other biological functions, ”added von Schacky.
In addition, several large studies with other omega-3 drugs produced mixed results: Most recently, AstraZeneca canceled its own study of Epanova, a mixture of EPA and DHA, last year after an independent committee was not convinced it was likely a positive effect on CVD. In this regard, Amarin’s positive results in recent clinical trials offer a rare track record.
Cover picture by Elena Resko. Body text image from Shutterstock