Recently, Amarin announced the successful completion of the Phase III EDPC003R01 study of VASCEPA (Ethyl Eicosapentaenoate Capsules) in treating patients with hypertriglyceridemia (≥ 500mg/dL) in Chinese Mainland.

At the end of the 12 week treatment period, the median triglyceride levels in the group receiving VASCEPA 4g/d were reduced by 19.9% compared to the placebo group. The subjects in the VASCEPA 4g/d treatment group did not show a significant increase in low-density lipoprotein compared to the placebo group. The results have significant statistical significance, meeting the primary efficacy endpoint defined in the clinical trial protocol and demonstrating safety similar to placebo, indicating that VASCEPA has a very important therapeutic effect on cardiovascular disease. On the day of the announcement of the results, Amarin's stock price also rose by 25% as a result.

As early as 2018, the same thing happened in the United States. On September 25, 2018, Vascepa successfully achieved the primary endpoint in the REDUCE-IT clinical trial conducted by VASCEPA! Compared to placebo, Vascepa reduced the risk of cardiovascular events by 25%, and as the only TG (triglyceride) drug supported by CV (cardiovascular disease) data at the time, Amarin's stock price skyrocketed threefold as a result.

Why can the same research be done again in a different place, causing such a big sensation? What are the differences between this Vascepa Phase III clinical trial?

Regarding VASCEPA

Amarin Corporation is a biopharmaceutical company founded in 1993, focusing on developing commercial cardiovascular disease treatment products in the United States. VASCEPA - Ethyl eicosapentaenoic acid capsules (EPA), is an Omega-3 fatty acid capsule (prescription drug), Amarin's leading product, used for patients with severe triglycerides. It is also the first and only single molecule prescription drug approved by the FDA (US Food and Drug Administration) containing highly purified active ingredient EPA ethyl ester.

Triglycerides and low-density lipoprotein

If you want to know why the VASCEPA clinical trial caused such a sensation, triglycerides and low-density lipoprotein are two essential key substances. Triglycerides are a type of fat and an energy substance that must enter the interior of cells in order to be utilized; Low density lipoprotein is also a type of fat, whose function is to transport triglycerides and other fats into the interior of cells. That is to say, without the transport of low-density lipoprotein, triglycerides cannot enter cells and therefore cannot function.

Under normal circumstances, triglycerides are continuously transported into the endothelial cells of blood vessels through the transport of low-density lipoprotein, and the cells continuously consume triglycerides. The two are in a dynamic balance, and there is not an excessive accumulation of triglycerides in the cells. However, when the endothelial cells of blood vessels are damaged and the levels of triglycerides or low-density lipoprotein in the blood are too high, there will be an excess of triglycerides transported to the cells. The more the excess triglyceride in the cell accumulates, the more it will cause inflammation and denaturation, forming a substance like "Congee". The cell is filled with a large number of such substances, which not only can not function normally, but also can be "broken" by these substances, causing damage and death. The normal structure of blood vessels is destroyed, and atherosclerosis and plaque occur, which is what we often call cardiovascular disease.

Cardiovascular disease has the highest mortality rate

The 2019 China Cardiovascular Health and Disease Report shows that the prevalence of cardiovascular disease in China is continuously increasing, with an estimated 330 million people currently suffering from cardiovascular disease.

In 2017, cardiovascular disease had the highest mortality rate, higher than tumors and other diseases. The mortality rate of cardiovascular disease in rural areas has exceeded and continued to exceed the urban level since 2009. In 2017, the proportion of cardiovascular disease deaths in rural areas to all causes of death was 45.91%; The proportion of urban cardiovascular disease deaths among all causes of death is 43.56%, which has increased to a certain extent compared to the previous year. In 2019, there were approximately 180.4 million patients with hypertriglyceridemia in China, accounting for approximately 20.2% of the adult population. Among all hypertriglyceridemia patients in China, approximately 9 million adults have extremely high levels of triglycerides (≥ 500mg/dL).

Unlike other Omege-3 products that only contain EPA, Amarin uses FDA regulated manufacturing processes from fish oil to purify high-purity EPA by removing other impurities. One important difference between it and other fish oil products is that other fish oil products contain Omege-3 fatty acids called DHA in addition to EPA. Can there be such a big difference just because of the difference in Omege-3 ingredients?

At the AHA conference held on November 14th this year alone, two sets of experiments on the effects of Omega-3 on cardiovascular disease were announced, namely the STRENGTH experiment led by the Cleveland Clinic Heart and Vascular Institute and the OMEMI experiment led by the Oslo University Hospital team. The final experimental data released from both experiments showed that there was no significant reduction in total cardiovascular events in cardiovascular disease, and Omega-3 supplements from both experiments showed a trend of increasing the risk of atrial fibrillation. The biggest difference between these two experiments and the Vascepa clinical trial is that Vascepa is a high-purity EPA, while the two experiments announced at the AHA conference used a mixture of EPA-DHA.

It can be speculated that previous clinical trials using fish oil ingredients to reduce cardiovascular disease risk have not yielded convincing results, and DHA may increase low-density lipoprotein levels, which may also be a potential reason why fish oil products have not significantly reduced cardiovascular disease risk in previous clinical trials.

Breaking through EPA purification technology barriers

Because fish themselves do not produce Omege-3, it is enriched through the consumption of microalgae. So Omege-3 derived from fish oil not only poses a risk of heavy metal pollution, but also has a fixed ratio of EPA to DHA that cannot be blended. Although current technology can separate EPA and DHA to obtain high-purity EPA and DHA, the cost of this process is very high, far exceeding the value brought by fish oil itself.