After AZ, another company's omega-3 drug failed in clinical practice

Compile newborn A few days ago, acasti pharmaceutical company (Kapre) (ω - 3 phospholipid) missed the main end point in the phase III Trilogy 1 study on the treatment of severe hypertriglyceridemia (blood level of triglycerides: 500-1500mg / dl) But acasti believes that there is still a chance for Capri, and the company says the study failed because of a strong drop in triglyceride levels in the placebo group Similar to vascepa and epanova, cppre is an omega-3-based drug designed to reduce the risk of cardiovascular disease and increase triglyceride levels in patients But it comes from prawn oil, not fish oil Acasti believes that the use of prawn oil as starting material will enable EPA and DHA, the main omega-3 components, to transport more efficiently, thus improving the absorption and reducing the synthesis of LDL-C To test this view, acasti initiated the Trilogy 1 study, which was tested in 242 patients with severe hypertriglyceridemia The patients were randomly divided into two groups They were given a daily dose of calcium or placebo for 26 weeks The results showed that after 12 weeks of treatment, the level of triglyceride decreased by 30.5% in the group of capre, which was favorable compared with the performance of vascepa Amarin showed that the level of triglyceride decreased by 27% during the development of the drug The problem, however, is that the effect of the cappre is not much better than that of the placebo In fact, after 12 weeks of treatment, triglyceride levels in the placebo group decreased by 27.5% There were also small differences in other related endpoints between the two groups, including a 26 week reduction in triglyceride levels (36.7% vs 28.0%), and a 12 week reduction in triglyceride levels (42.2% vs 31.5%) in the subgroups of patients receiving background statins It is also worth noting that triglyceride levels in both the placebo group and the Capri group experienced significant reductions in the first four weeks of the study (baseline 0-4 weeks) The placebo used in the trilogy study was corn starch, a complex carbohydrate with a low glycemic index, so a neutral effect was expected on key biomarkers in the placebo group According to acasti, the existing data reveal an unusually strong placebo effect, leading to a statistically significant difference in the Trilogy 1 study The company has made statistics on a number of previous clinical trials of reducing triglyceride by omega-3 preparation with similar prescriptions The results show that the drop of triglyceride level related to placebo in most trials is no more than 10%, and the maximum drop is 17% Specifically, the placebo effect (using corn oil, olive oil or vegetable oil) ranged from + 16% to - 17% in 18 intervention groups, of which 14 intervention groups ranged from + 10% to - 10% In the vascepa study, triglyceride levels increased by 10% in the placebo group To explore Trilogy 1 Placebo effect of up to - 27.5% in the study Acasti conducted a preliminary analysis on 5 of the 54 clinical centers of the enrolled patients, and found that these 5 research centers "have a disproportionate contribution to the overall effect of placebo", which prompted the company to start to review the original data and patient records collected by all 54 clinical centers, and at the same time, they will be used in the screening process or in the trial process Whether patients continue to take or discontinue other lipid-lowering drugs for investigation, the review results are expected to be published next month If the investigation comes to a reasonable explanation, acasti believes that the company may still have a path to submit the listing application of Capri to FDA The availability of this route depends on the results of a second phase III study, Trilogy 2, whose top line results are expected to be published in March this year However, investors are still pessimistic about the cppre On the day of Trilogy 1 research results, the market value of acasti evaporated by two-thirds However, some analysts pointed out that although on the surface, the successive failure of two competitors is beneficial to amarin, in the long run, it may not be a good thing, especially now the mechanism of vascepa is not clear, and the failure of the same type of drugs will make doctors less confident Therefore, in order for amarin to truly benefit, it is necessary to provide evidence that vascepa is not the same "product" as epanova and Capri.