麻豆传媒

PHILADELPHIA -- Diabetics with mixed dyslipidemia who were on statins improved their lipid profiles, without worsening glycemic control, with a novel omega-3 fatty acid drug, according to researchers here.

In a subgroup analysis of the ANCHOR study, the drug AMR101 at 4 g/day significantly reduced triglycerides by a mean of 23 mg/dL, whithout raising low density lipoprotein cholesterol (LDL-C) in the population of all patients with diabetes, reported Eliot Brinton, MD, from the Utah Foundation for Biomedical Research in Salt Lake City, and colleagues. AMR101 is 96% pure eicosapentaenoic acid (EPA).

The drug also significantly reduced most lipid and lipoprotein parameters, including triglycerides, non-high density lipoprotein cholesterol (HDL-C), very LDL-C, lipoprotein-associated phospholipase A2, apolipoprotein B, and total cholesterol, Brinton reported at the annual meeting of the American Diabetes Association.

"Many of these effects were greater among those with less-controlled diabetes, suggesting that AMR101 may be especially useful in patients with diabetes when good glycemic control has not been or cannot be achieved," the researchers said.

The mean baseline LDL-C was 81 mg/dL and the mean reduction at 12 weeks follow-up was 6.3 mm/dL for those taking 4g/day.

The one negative finding of this ANCHOR subgroup analysis was a significant mean decrease in HDL-C of 5 mg/dL from a mean baseline level of 36 mg/dL (P<0.01). But "the drops in LDL cholesterol, non-HDL cholesterol, apo B, and total cholesterol were greater on a percentage basis and tended to be a more robust statistical finding," Brinton told 麻豆传媒.

In the phase III ANCHOR study, the drug was evaluated in 702 patients on background statins whose residual triglyceride levels were between 200 and 500 mg/dL. Patients were randomized to 2 or 4 grams of AMR101 or placebo.

In the current analysis, the effect was dose-dependent, with fewer significant reductions in the arm taking 2 g/day. The reduction in LDL-C at either dose was not significant.

The 12-week study indicated the drug is safe for diabetics, as no statistically significant changes were seen in fasting plasma glucose, hemoglobin A1c, homeostasis model index insulin resistance (HOMA-IR), or insulin.

The novel agent also seemed to confer anti-inflammatory and anti-oxidative benefits, Brinton said.

Researchers observed significant reductions in high-sensitivity C-reactive protein (hsCRP), oxidized LDL, and remnant-like particle cholesterol (RLP-C), which "suggests there will be a reduction in cardiovascular events," Brinton said.

The current subgroup analysis included 501 diabetics. The median baseline HbA1c was 6.8%, with a nearly equal number above and below that threshold.

Brinton noted that the purification process of the drug is expensive, and its price point and marketing will determine how well received it will be if it is approved.

Previous data on the value of omega-3 fatty acid in this patient population has been mixed. When ANCHOR was presented at the 2011 American Heart Association meeting, cardiologists at the time were not overwhelmed. Many said that if patients inquire about fish oil, they are told to buy supplements.

In the MARINE trial, AMR101 was tested in 239 patients with triglycerides above 500 mg/dL with or without statins. Amarin Pharma, the drug's manufacturer, filed an application with the FDA for approval on the basis of the MARINE results. The FDA requested an outcomes study, which led to the initiation of the REDUCE-IT trial.

Investigators are currently enrolling patients into REDUCE-IT, which is evaluating the effect of AMR101 on prevention of a first major cardiovascular event.

The JELIS (Japan EPA Lipid Intervention Study) study, which evaluated a similar drug, found a 19% relative reduction in all-cause mortality at 5 years, Brinton said, adding that the dose in REDUCE-IT will be more than double that in JELIS.

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