The two drugs were under by AstraZeneca (Epanova) and Acasti Pharma (CaPre). Epanova, a mixed EPA and DHA product developed from fish oil, was being studied in a large scale trial called STRENGTH.
AstraZeneca trial shows no benefit
AstraZeneca has structured the trial with a 4 gram dosage and an endpoint of reducing major adverse cardiovascular events (MACE) in a population of subjects with mixed dyslipidemia. MDL includes patients with raised triglyceride levels (moderate hypertriglyceridemia) between 175-499mg/dL mg/dL, and low HDL cholesterol. The trial included 13,086 patients at 675 sites in 22 countries. A placebo made of corn oil was used.
The drug company announced on Monday that the trial had been halted because no statistically significant positive benefits were being observed. While the cessation of the trial is obviously not good news, it didn’t seem to hurt the company’s stock, which continues to trade at around $50 a share. Stock analysts predicted that the drug’s problems might cause as much as a $100 million write off, which could hurt the company’s results in the next quarter. But AstraZeneca brings in more than $22 billion a year.
The news did moderately benefit a smaller competitor, however. Amarin, which markets Vascepa, an EPA-only fish oil drug, saw its shares rise from $18.95 to $20.58 in the minutes after the announcement. But the shares have since receded, and Amarin’s shares hit their high point of more than $24 a share in December.
Acasti’s trial marred by huge placebo effect
In the other clinical trial, on Monday Canadian drug company Acasti Pharma released preliminary results of the clinical trial of its krill oil drug CaPre, which is being studied for its effect in lowering very high blood trigylceride levels. The preliminary results showed that CaPre had significantly lowered these levels. But the trial also showed a confoundingly high placebo effect, so in the end the drug performed no better than the placebo.
Stock traders were quick to punish Acasti, which unlike AstraZeneca is still a development stage company. The company’s stock price declined from $2.14 a share on Monday to about 50 cents a share in the minutes after the announcement. The shares are still trading at about 85 cents a share today.
Results of drug trials are in any case only applicable to the materials studied, strictly speaking. But positive results in the past have been welcomed by observers and companies in the business as providing proof that the products, when taken as an entire group, have some benefit. Aker BioMarine CEO Matts Johansen (Aker supplies the raw material for CaPre) had been looking forward positive news about the drug development as a way to boost the overall krill oil supplements category.
"Based on the limited information that Acasti made public regarding the results from the TRILOGY 1 Phase 3 Trial clinical trial, we recognize that the study observed very significant median reductions in plasma triglyceride levels, even better than what has been recorded for other long chain omega-3 based medications. Therefore, it is very surprising that significant reductions were observed not only in the CaPre groups, but also for the cornstarch placebo. Reduction of plasma triglycerides from very elevated levels is considered an objective endpoint that typically would not be expected to be prone to significant placebo effects. Consequently, further conclusions on the matter should only be made after further investigations have been reported," Johansen said.
Ultimate import of trials’ failure unclear
Dr William S. Harris, one of the world’s foremost academic experts on omega-3s, said it’s far too early to know exactly what happened in these trials, so the import for the entire sector is still unclear. Harris is a professor at the Sanford School of Medicine at the University of South Dakota. He is also the founder and CEO of omega-3s testing firm OmegaQuant and is the codeveloper of the Omega 3 Index.
“For the STRENGTH trial, it really depends on what the cause of the non effect was. We won’t know that until sometime later. My assumption is that they’ll report the full results at the AMA meeting in November,” Harris told NutraIngredients-USA.
“When you look at what happened in the VITAL trial (an omega-3s plus vitamin D large scale trial) there was an overall null effect for omega-3s but when you looked at heart attacks specifically, they were significantly reduced,” he said.
“The same kind of thing might happen here, showing some benefits in some subcategories but not the overall category. And we don’t know what blood levels of omega-3s they achieved in this study,” Harris added.
“This trial was done in 26 countries, so maybe the background diets had some influence. Maybe the story here will be that EPA alone is way better for heart health than EPA plus DHA,” he said.
Harris said there might also be an issue with the free fatty acid form the drug company chose for the drug.
Harris said in his view the overall strength of evidence backing the effects of omega-3s is clear and cannot be refuted. But when delving down into pharmaceutical type studies, where modes of action and pharmacokinetics are of paramount importance, the issue becomes less clear.
“It’s very humbling. We think we know what’s going on, what the lay of the land is, and then something like this happens,” he said.