Joanna Cosgrove11.08.10
For patients with hypertriglyceridemia—a dangerous condition characterized by a triglyceride level over 500 mg/dL—a popular and effective therapy of late has been the fish oil-based pharmaceutical Lovaza from GlaxoSmithKline (GSK)*, coupled with statin therapy. But a new, more specialized fish oil medication from Amarin Corp., of Dublin, Ireland, recently entered Phase III clinical trials and is poised to siphon valuable market share from Lovaza.
Dubbed AMR101, the product is an ultra pure (>96%) ethyl ester of eicosapentaenoic acid (ethyl-EPA), a long chain highly unsaturated fatty acid in the omega 3 class. Amarin believes the product to have a beneficial impact on such biological factors as anti-inflammatory mechanisms, cell membrane composition and plasticity and regulation of glucose metabolism, though its impact on triglyceride levels is an area buoyed by the most clinical promise.
In an interview with Nutraceuticals World, Declan Doogan, MD, Amarin’s chief medical officer, talked about three key points of difference that will likely pit AMR101 squarely against GSK’s Lovaza.
For starters, AMR101 is pure EPA and doesn’t contain any DHA. Amarin is confident that the absence of DHA confers distinct advantages in the quest to lower high triglycerides. “DHA is associated with elevations in LDL cholesterol. Because AMR101 doesn’t have DHA, we believe we will be without the LDL signal to the same extent as Lovaza,” he explained. “What’s important to understand is that Lovaza, when given with a statin is still associated with an elevation of LDL so therefore in many cases you would still have to adjust the dose of the statin. AMR101 is cleaner in that when you combine AMR101 and a statin, you should not get this LDL change. We believe it will be an easier drug for doctors to prescribe than Lovaza.”
In addition to cutting out the DHA effect, AMR101 has also demonstrated its efficacy in half the dose of Lovaza. “The dose of Lovaza is four grams (or four capsules) per day for patients with very high triglycerides of 500 or above,” Dr. Doogan said. “With AMR101 the dose is likely to be two grams or two capsules for the same population, which is still to be proven in our clinical trials but that’s the plan.”
The third differentiation relates to the medication’s lack of a fishy aftertaste, which Dr. Doogan attributed to the nonexistence of DHA in the formulation.
“The question may be asked ‘Yes, but what do you lose by taking DHA out of AMR101 or fish oil?’ I don’t believe you lose anything,” he said. “If you’re using this drug as a treatment for vascular disease and cardiovascular complications, we have data to show in 19,000 patients if you add AMR101 or 96% EPA to a statin, compared with a statin alone you will get an additional 19% reduction in coronary events. You turbo-charge the statin when you give AMR101. That’s saying that pure EPA alone will do the business.”
He also added that although DHA is excluded from AMR101 it doesn’t mean DHA doesn’t have a place in the nutraceutical landscape. “DHA is an integral component of nutritional supplements and food preparations for children, such as baby formulas,” he said. “It’s very important for the maturing brain and retinas. But that’s a very different proposition than managing adult cardiovascular events.”
He additionally acknowledged the benefits of nutraceutical grade omega 3. “I understand the value of nutraceutical supplementation of omeg -3 as well as the nutraceutical market for omega 3. As a physician, I would recommend omega 3 as a wellness product,” he said. “But when somebody comes to the doctor with substantially elevated triglycerides (500+) I would strongly believe that the doctor would want to prescribe a well-tried and tested formulation and dose of omega 3 and that’s the reason for the likes of Lovaza and AMR101.”
Mounting Research
Amarin’s AMR101 EPA formulation is not entirely unique, as pure EPA has been available in Japan (marketed by Mochida as Epadel) for a decade and has been extensively researched. In fact, according to Amarin, a study called JELIS demonstrated that EPA plus statins reduced coronary events in at-risk patients by about 19% compared to statins alone. Based on this evidence, there is quiet confidence that the two current Phase 3 AMR101 trials will be successful.
The first trial, called Marine, is set to examine about 250 of the same patients targeted by Lovaza—those, for example, who have triglyceride levels above 500 mg/dL.
The second trial, called Anchor, will look at patients with triglyceride levels above 250mg/dL and below 500 mg/dL, who also are receiving statin therapy for high LDL cholesterol. This group has what is referred to as mixed dyslipidemia. According to Amarin, this trial aims to extend the prescription label for AMR101 to a population that Lovaza is not approved to treat.
There are approximately 10 times more patients in this group than the population Marine/Lovaza targets. This trial is expected to complete recruitment of approximately 650 patients in early 201.
“We have masses of data on the drug to show that it’s safe and to show our confidence in the drug’s effect on triglycerides and also cardiovascular disease,” Dr. Doogan concluded.
Results for the Marine trial are expected in early 2011, with Anchor trial results to follow. Dr. Doogan said he expected an application to the FDA to be filed shortly thereafter.
*When contacted, GSK declined the opportunity to make a statement, citing company policy not to comment on products that are not yet at market.
