In the world of health, fish oil has been a wonder child product these last few years. From claims of cardiac protection, cancer prevention, and skin health most patients in my office are taking OTC fish oil on a regular basis. And why not? Fish oil has no known major life threatening side effects (unless you are allergic to fish or shellfish), other than the "fishy smell" from an occasional belch.
Of the numerous fish oil products in the market, there is only one available prescription fish oil in the US - Lovaza. Lovaza is made from omega-3 fish oil and sold by GlaxoSmithKline (GSK) with the indication of lowering very high triglycerides (over 500 mg/dL). Each gram of Lovaza contains a combination of EPA and DHA ingredients.
A number of factors can increase the risk for high triglycerides (TG) - weight (obesity), alcohol intake, high cholesterol, diabetes, and most commonly - refined carbohydrate intake (white bread, white rice, potatoes, pasta, etc). Looking at these risk factors, it's not a surprise that a significant number of patients have elevated triglycerides. The major risk for high triglycerides is cardiovascular disease - a leading cause of death in the United States.
Despite its relatively low profile side effects, Lovaza has current limitations:
1. It is FDA Approved for Very High Triglycerides only (>500 mg/dL) - most patients who have elevated triglycerides range between 200-500 mg/dL.
2. Lovaza may increase LDL Cholesterol ("bad cholesterol") - it's no fun trying to lower one type of bad lipid while knowing there is a risk of increasing the other type of bad cholesterol.
3. The recommended dose is 4 capsules a day (4 grams total). For some folks, it's hard enough just to take one capsule a day.
4. GSK currently has this statement about Lovaza: "Treatment with Lovaza has not been shown to prevent heart attacks or strokes."
In the coming months, Lovaza has reason to worry. Amarin (AMRN) is a clinical-stage biopharmaceutical company with a potential blockbuster Fish Oil product - currently known as AMR101. AMR101 is different from Lovaza in that it primarily contains EPA fish oil (Lovaza has EPA and DHA).
Amarin has completed two Phase 3 studies of AMR101. The MARINE study reported in November 2010 demonstrates that AMR101 not only effectively lowered TG levels in patients with very high TG ( > 500 mg/dL) - similar to Lovaza, but without significantly increasing "bad" LDL cholesterol (superior to Lovaza). In addition, The MARINE trial results also showed favorable findings with reductions in total cholesterol, non-HDL-C, Apo B (Apolipoprotein B), and Lp-PLA2 levels, together with a safety profile for AMR101 comparable to placebo. The trial's primary end point was met with BOTH the 4 gram dose group (4 capsules a day) and the 2 gram dose group (only 2 capsules a day).
Amarin is waiting an FDA decision on AMR101 approval in July 2012 for the indications being studied in the Marine Trial.
The ANCHOR trial studied the safety and efficacy of 2 grams and 4 grams of AMR101 in patients with high triglycerides (>200 and <500 mg/dL) who are on statin therapy (popular class of cholesterol lowering medication). In April 2011 Amarin reported positive results for its primary end point of lowering TG and announced that it also achieved its secondary endpoint - "bad" LDL cholesterol did not increase significantly.
With the results of the ANCHOR trial, Amarin has bridged a "gap" of treatment criteria that was unfulfilled by Lovaza:
- AMR101 successfully treated patients with triglycerides between 200-500 mg/dL - Lovaza is FDA approved for only patients with TG above 500 mg/dL. Most patients with elevated TG fall within this 200-500 mg/dL TG range.
- AMR101 does not increase "bad" LDL cholesterol, whereas Lovaza has the LDL cholesterol label warning.
Amarin intends to submit a Supplemental NDA (SNDA) seeking approval for the ANCHOR indications once its REDUCE-IT cardiovascular outcomes trial is substantially underway.
The REDUCE -IT (Reduction of Cardiovascular Event with EPA - Interventional Trial) Outcomes trial: Amarin is planning to undergo this 6 year-trial to evaluate the effectiveness of its fish oil in reducing the first major cardiovascular events in patients who are in a at-risk population. If this trial shows positive results, it will shift the paradigm of medical treatment using using fish oil in cardiovascular disease prevention.
Click Here for Amarin info.
Disclosure: I am long AMRN.