Last month’s EU approval of Vazkepa — a treatment derived from fish oil and branded as Vascepa in the US — has added much-needed ammunition to the arsenal of doctors battling cardiovascular disease. Yet other similar treatments are returning lukewarm results and the possibility of approvals being withdrawn hangs in the air.
Icosapent ethyl, a derivative of fish oil formulated by US-Irish biotech Amarin, recently became the first approved treatment in the EU to reduce the risk of strokes and heart attacks in patients with elevated triglycerides—a type of fat—who have previously been treated with statins.
The approval addresses a pressing medical need. Cardiovascular disease (CVD) is the leading cause of death worldwide, according to the World Health Organization. In Europe, over 60 million people suffer from CVD, and the cost to the economy is estimated at around €210B per year.
Icosapent ethyl is a purified form of EPA, one of two major omega-3 fatty acids found in fish oil, the other one called DHA. The drug, marketed in Europe under the name Vazkepa, was initially approved by the FDA in 2012 under the brand Vascepa to reduce blood triglyceride levels in people with hypertriglyceridemia. In 2019, the FDA expanded Vascepa’s indication to reduce the risk of stroke and heart attacks in high-risk patients, following a phase III clinical trial that showed it reduces the risk of adverse cardiovascular events by 25%.
Exactly how Vascepa had such a profound benefit in this trial is still largely unclear. According to results from a different clinical study, statin-treated patients with high triglycerides given Vascepa saw a significant 17% drop in the buildup of low attenuation plaques, a type of coronary plaque.
“Coronary plaque stabilization is an important finding with Vascepa and may explain, in part, the substantial cardiovascular benefit seen in [the previous phase III study],” commented Craig Granowitz, Amarin’s CMO, in a recent press release.
Amarin representatives did not respond to requests for further comments. The company, which posted record revenues in 2020, is currently going through a CEO reshuffle and a bitter patent litigation after a US court invalidated its patents on Vascepa last year, leaving the drug open to competition from generics. Consequently, big hopes rest on its performance in the EU market, where it still holds patents for the drug.
Independent observers heralded the decision by the European Commission as a breakthrough both for fish oil products and for cardiovascular treatments.
“While we do not have any opinion on any specific product, we warmly welcome the development of new treatments for CVD conditions,” Birgit Beger, CEO of the European Heart Network, told me. “Innovation in CVD as regards new active substances or new therapies is very slow.”
Over a dozen CVD treatments have been approved by the EMA in the past five years, yet the vast majority were generics or biosimilars.
“The development pipeline is stronger in the USA, clinical trials are moving out of Europe and China has a fast-growing share in cardiovascular research and development,” Beger added.
“Europe as a whole still has a competitive research output and capacity, supported by research networks, partnerships, and European infrastructure but will need to become more effective at translating science into clinical solutions and products.”
Fish oil-derived treatments have also had a rollercoaster recent history, both in clinical trials and in the business world. They have been considered by scientists as a potential panacea for anything from CVD to brain disease to Covid-19. Yet they often get stuck in the no man’s land between food supplements and drugs, a divide that in recent years has grown complicated.
While the EMA is responsible for drugs, food supplements are regulated separately by the European Food Safety Authority (EFSA). The views of the two on fish oils and heart disease have fluctuated over the years and “are not exactly identical,” said Clemens von Schacky, a German cardiologist and the CEO of German commercial testing lab Omegametrix.
Approvals of all medicines based on EPA and DHA mixes to reduce cardiovascular risk were withdrawn by the EMA in 2018 after the regulator concluded that there wasn’t enough evidence to support their benefits in this indication — though they are still approved to lower triglycerides. Meanwhile the EFSA continues claiming that EPA and DHA contribute to normal cardiovascular functions. These differences, alongside issues of reimbursability and competition from generics, have wreaked havoc on companies’ business plans.
Part of the complexity of the issue may be that omega-3 treatments are most effective when there is a deficiency involved. Deficiencies, though, typically involve both EPA and DHA. This is also a reason why Vascepa’s remarkable success in clinical trials has raised some eyebrows in the scientific world.
“One problem with Vascepa is that it contains only 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 build-up and maintenance of the brain, and a host of other biologic functions,” von Schacky added.
Furthermore, several large trials of other omega-3 medicines returned mixed results: most recently, last year AstraZeneca stopped its own trial of Epanova, a mixture of EPA and DHA, after an independent committee was not convinced of the likelihood that it would have a positive impact on CVD. In that respect, Amarin’s positive recent clinical trial results offer a rare success story.
Cover image from Elena Resko. Body text image from Shutterstock