Wednesday, March 16, 2011

Euthymics Bioscience Initiates Triade Trial For Major Depression

Euthymics Bioscience, Inc. announced the initiation of an advanced clinical study of its lead product candidate EB-1010 for the treatment of major depressive disorder (MDD). The TRIADE (Triple Reuptake Inhibitor Anti-Depressant Effects) trial is a phase 2b/3a clinical trial designed to assess the safety and efficacy of EB-1010, a novel serotonin-preferring triple reuptake inhibitor. The trial will be conducted at 25 centers throughout the U.S., and Euthymics plans to enroll approximately 300 individuals. Patient recruitment is now underway and top-line results are expected in mid-2012.

Euthymics' EB-1010 acts on three neurotransmitters-serotonin, norepinephrine and dopamine-in a ratio of 1 to 2 to 8. EB-1010 is intended for patients with major depressive disorder who do not respond adequately to a single course of selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs), the most common medications in the $20 billion global antidepressant market. However, a large subset of patients with major depressive disorder, about 66%, do not experience remission after initial treatment with SSRIs, according to the STAR*D study, a large seven-year study sponsored by the National Institute of Mental Health. Even substituting an SNRI did not improve outcomes. However, STAR*D also showed that outcomes improved when patients were treated with multiple medications to modulate serotonin, norepinephrine and dopamine. EB-1010 recapitulates this triple profile in a single molecule.

"There is great need for an effective medication with a favorable side effect profile for the millions of patients who do not respond fully to or are not compliant with current antidepressant treatments, such as SSRIs or SNRIs," said the principal investigator of the TRIADE study Maurizio Fava, M.D., Professor of Psychiatry at Harvard Medical School and Executive Vice Chair of the Department of Psychiatry at Massachusetts General Hospital. "It is exciting to be involved in the study of this novel serotonin-preferring triple reuptake inhibitor."

The TRIADE trial (also known under the protocol number EB-1010-301) is a phase 2b/3a trial testing both the efficacy and safety of EB-1010 and comparing to it to placebo and a standard treatment. TRIADE is a 12-week double-blind, placebo-controlled trial intended to measure changes in the Montgomery-Åsberg Depression Rating Scale (MADRS), a standard measure of depression. Secondary measures include sexual function, weight gain and cognition. The trial will use an advanced study design called Sequential Parallel Comparison Design (SPCD), a clinical trial methodology co-invented by Dr. Fava, to increase efficiency and reduce confounding placebo responses, a major issue in clinical trials for depression. The trial will have four arms: two doses of EB-1010 (standard dose 100 mg and half dose 50 mg), a placebo arm, and-under SPCD protocol-there will be an active comparator arm with subjects receiving paroxetine (Paxil®). 
Results of a previous phase 2 trial presented at the 2010 annual meeting of the American College of Neuropsychopharmacology (ACNP) showed that EB-1010 was effective in treating MDD based on multiple standard measures of outcome. The trial also showed that EB-1010 improved measures of anhedonia and was well tolerated, without the weight gain or sexual dysfunction associated with the most common pharmacological treatments for depression.

Anthony A. McKinney, President and CEO of Euthymics, said, "The promising results we reported previously at ACNP provided important validation for the potential of EB-1010's unique profile to treat a large segment of the patient population with major depression. We believe EB-1010 has the potential to become the first triple reuptake inhibitor to achieve the efficacy of multiple neurotransmitter reuptake inhibitors in a single medication, and we are eager to further evaluate its potential with the TRIADE clinical trial."

As a serotonin-preferring triple reuptake inhibitor, EB-1010 demonstrates greatest affinity for the transporters for serotonin reuptake; it is half as potent for norepinephrine and has one-eighth the potency for dopamine, resulting in a ratio of 1:2:8. This is in contrast to balanced triple reuptake inhibitors which have equal affinity for the three monoamines, and have not demonstrated efficacy in depression. EB-1010 is delivered as monotherapy without the cost or complexity of multiple prescriptions. 

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