BioWorld Today Contributing Writer

Omthera Pharmaceuticals Inc., of Bedminster, N.J., raised $33.9 million in Series B funding and initiated Phase III trials for Epanova, its candidate for high triglycerides. The capital raised will support development of Epanova, which could take a bite out of the $2 billion worldwide market for prescription omega-3 fatty acid.

"We sought out some of the best venture capital firms in the industry," Omthera CEO Jerry Wisler told BioWorld Today.

The cash infusion is expected to keep Omthera afloat "well past" its new drug application (NDA)," according to Wisler, who said the company plans to file in 2012.

New Enterprise Associates led the financing, joined by Sofinnova Partners. The funding will be funneled into clinical development of Epanova, particularly its Phase III EVOLVE trial.

The EVOLVE trial will be a 12-week, multicenter, randomized, double-blind, placebo-controlled study to evaluate safety and efficacy of three doses of Epanova in patients with fasting triglyceride levels over 500 mg/dL. It will enroll 330 patients randomized into four groups with a primary endpoint of percentage change in triglyceride level and a secondary endpoint of reduction of non-HDL cholesterol.

The trial was granted a special protocol assessment from the FDA.

Omthera recently reported data from the Phase I/II ECLIPSE trial testing Epanova against Lovaza for treating very high triglycerides (500 mg/dL or higher).

Data showed that the bioavailability of Epanova was superior to Lovaza, with plasma levels of EPA plus DHA four times higher in subjects on a low-fat diet who received Epanova vs. Lovaza.

Significantly higher plasma levels also were seen in patients on a high-fat diet receiving Epanova compared to Lovaza. In a separate analysis, Epanova demonstrated a 13-fold increase in bioavailability of EPA over Lovaza in subjects consuming a low-fat diet in the study. (See BioWorld Today, Nov. 23, 2010.)

Omthera acquired Epanova from Basel, Switzerland-based Tillotts Pharma AG in 2009. Tillotts had been testing the drug in patients with Crohn's disease in a Phase III trial.

While Epanova did not reach the trial's primary endpoint of symptom reduction in Crohn's, it did lower levels of triglycerides in the Crohn's patients. Those patients did not have excessively high levels of triglycerides. Omthera expects Epanova to be more even effective in lowering very high and high levels of triglycerides. (See BioWorld Today, Nov. 23, 2010.)

Epanova's main difference from Lovasa is that it is formulated as a free fatty acid, not an ethyl ester. Crude fish oil is found in a triglyceride form, and Lovaza is made by converting that triglyceride into an ethyl ester.

"We take it a step further from an ethyl ester to a free fatty acid," Wisler said.

Omthera credits its free fatty acid formulation for the product's superior bioavailability. Normally, when fish oil is consumed, the body must convert the triglyceride or ethyl ester form into a free fatty acid using pancreatic lipases. However, pancreatic lipases are only excreted in response to fat consumption, and most patients with extremely high triglycerides are on a low-fat diet.

According to Wisler, Epanova is much more compatible with a low fat cardiac diet than Lovasa. "The free fatty acid is well-absorbed regardless of the type of meal," Wisler said.

In addition to lining up against market leader Lovaza, Epanova could face competition from Amarin Corp. plc's AMR101 (ethyl icosapentate).

Amarin's strategy for AMR101 was to formulate a product containing 96 percent pure ethyl ester of eicosapentaenoic acid (EPA), rather than a mixture of EPA and docosahexanoic acid (DHA), which most omega-3 supplements contain.

Epanova and Lovaza contain mixtures of EPA and DHA.

The difference is important, according to Amarin, because DHA has been known to raise levels of LDL cholesterol. In a pivotal Phase III trial, AMR101 lowered triglycerides without increasing LDL. (See BioWorld Today, Nov. 30, 2010.)

With Amarin on deck to file an NDA as early as 2011, 2012 could see a battle of the paradigms, as Epanova and Amarin duke it out to see whether bioavailability can trump an EPA-only strategy, or vice versa.

"We expect Epinova will be best in class, and post launch will be the market leader," Wisler added.

In other financing news:

• Biotie Therapies Corp., of Turku, Finland, completed a private placement of nearly 50 million shares at €0.54 per share ($0.7539) for a total of €27 million. The total number of shares outstanding after the offering will be 387,594,457, and Biotie's cash equivalents and short-term investments will total more than €45 million. Following the offering, Biotie has agreed not to issue or sell any shares for 180 days. Biotie stock (XHEL:BTH1V) closed at €0.52 Monday.

• Ottowa, Ontario-based PharmaGap Inc.'s Feb. 24 private placement was oversubscribed by C$34, 165 (US$35,019), bringing the full amount to $1,034,165.1.804 million units will be issued at 11 cents per unit. Each unit is comprised of one common share and one warrant to purchase a common share at 16 cents. Closing is expected to occur on March 14, subject to approval of TSX Venture Exchange.