Essentialis receives agreement from the FDA for Phase III trial of DCCR

Therapy is designed to help the millions of people suffering from very high triglyceride levels

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SAN DIEGO—Essentialis Inc. announced Oct. 25 that it has reached agreement with the U.S. Food and Drug Administration (FDA) on a Special Protocol Assessment (SPA) for a Phase III efficacy study required for product registration for its product candidate, Diazoxide Choline Controlled Release Tablet (DCCR), for the treatment of patients with very high triglycerides.  Essentialis and FDA agreed upon the patient population to study, inclusion and exclusion criteria, study duration, dosage, endpoints and their analyses.

The double-blind study includes two dose levels of DCCR as well as placebo and active control arms. Half of the patients in the study will be statin treated, providing data supporting approval for co-administration with statin. The primary endpoint is percent change from baseline for triglycerides. Secondary endpoints include percent change in non-HDL cholesterol and Apo B. Exploratory endpoints include such non-lipid cardiovascular risk factors as blood pressure and waist circumference.

In May 2009, the company had reported that it met its primary endpoint of statistically significant triglyceride reduction in a 90-patient Phase IIb trial of DCCR in dyslipidemic patients. The study encompassed both patients with very high triglycerides and mixed dyslipidemia and included normal weight, overweight and obese patients presenting with or without hypertension. That randomized, double-blind study, which Essentialis reports was "powered as if it were pivotal," assessed the drug's  effect on dyslipidemia and evaluated three different doses of DCCR given over an eight-week period compared to placebo.

The study included 90 subjects with high and very high triglycerides as well as subjects on stable doses of statins. At the end of eight weeks, treatment with DCCR resulted in a 30 percent placebo-adjusted median reduction in triglycerides. The reduction was considered clinically relevant, highly significant and competitive with existing approved drugs. In subjects with very high baseline triglycerides, DCCR treatment reportedly resulted in a substantially greater reduction in triglycerides.

"We are very pleased with the FDA's decision, as we believe the data which will be obtained in the proposed trial is anticipated to support the approval of DCCR in the patient population studied, the millions of people with very high triglycerides," said Dr. Neil Cowen, president and chief scientific officer for Essentialis, with regard to the October 2010 announcement.

Currently, there are a limited number of therapeutic options for the treatment of very high triglycerides, but only DCCR works primarily by significantly reducing the production by the liver of harmful triglyceride-rich lipoprotein particles, Cowen says. "Due to the unique mechanism of action, DCCR has the potential to be an important advance in the treatment of patients with very high triglycerides," he adds.

"The positive outcome of the SPA process means Essentialis has now reached a major developmental milestone for DCCR," says Aaron Berg, chief commercial officer for Essentialis

Berg reported in mid-October that Essentialis raised Series B funding over the summer, though he didn't disclose the amount.

He indicates that some of the aspects of DCCR that make it an attractive prospect for investment are that it seems to lower triglyceride levels in a manner comparable to Lovaza, a drug now used to prevent pancreatitis among patients with high triglycerides, but dodesn't seem to increase low density lipoprotein—while GlaxoSmithKline's Lovaza does sometimes have that effect.

Essentialis' leaders don't expect that it will need to prove that DCCR reduces the number of pancreatitis cases to gain U.S. approval. Demonstrating an ability to lower triglyceride levels should be sufficient, Berg says.

If Phase III trials actually begin this year, the drug could earn U.S. approval in 2013, Berg says.

DCCR has other effects that might Essentialist to expand its market potential. Patients with high triglycerides may have other medical problems, such as obesity and hypertension, and DCCR has shown an ability to reduce waist circumference. It also has what Essentialis calls "a modest but significant" ability to lower both diastolic and systolic blood pressure.

Berg says that because patent protection on DCCR extends to 2028, there is plenty of time for running additional studies to expand the drug's label and to help the company and its investors realize a bigger return on investment.

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