Embera’s Combination Treatment: EMB-001

EMB-001 is a patented combination product comprised of two FDA-approved medications, the cortisol synthesis inhibitor metyrapone and the benzodiazepine oxazepam. The innovation is based on insights into the physiological responses to stress in addiction.

The goal of addiction treatment is long-term abstinence, and to accomplish this, one must minimize relapses.  There are three well-characterized causes of relapse:  stress-induced (such as family conflict), cue-induced (environmental triggers like seeing drug paraphernalia) and drug-induced (even small exposures renewing addiction).  In addition to stressors, both cues and drug exposure lead to stress responses.  Therefore, it is theorized that modulating stress response pathways may reduce all 3 sources of relapse.

By combining two medications that work on different aspects of the physiological stress response, at lower doses, EMB-001 may maximize potential efficacy more than either drug used alone. A therapy that breaks these barriers and results in long term abstinence and recovery would be a significant contribution to the treatment of a broad range of addictions.

Clinical Development

Embera completed a randomized, double-blind, placebo-controlled, single- and multiple-dose, Phase 1 safety and pharmacokinetics (PK) study in smokers. EMB-001 met the primary goals of  the study. Treatment was well tolerated and PK results suggested that twice-daily dosing may provide appropriate exposure for efficacy. In addition, exploratory smoking measures showed encouraging results to support a planned Phase 2a study in tobacco use disorder. Results from the Phase 1 study were presented at the Society for Research of Nicotine and Tobacco (SRNT) Annual Meeting, the American Society of Clinical Psychopharmacology (ASCP) Annual Meeting, and other scientific conferences in 2016. Based on these results, Embera is advancing the EMB-001 cocaine use disorder and tobacco use disorder programs to the next stage of clinical development.

Previously, Embera completed a randomized, double-blind, placebo-controlled pilot clinical study of EMB-001 in cocaine-dependent (per DSM-IV) subjects. EMB-001 treatment resulted in significantly reduced cocaine use, compared to placebo, by the end of the 6-week study. Additionally, treatment with EMB-001 led to significant reductions in cocaine craving at several time points during the study and was well-tolerated over the six-week treatment period. Results were published in Psychopharmacology in 2012.

The Company’s clinical development program is also supported by positive preclinical studies in which EMB-001 reduced self-administration of nicotine, as well as cocaine and methamphetamine, in relevant models of addiction. In the nicotine study, EMB-001 also demonstrated a statistically significantly greater effect relative to varenicline (Chantix®), the clinical market leader for smoking cessation efficacy. Cocaine studies of EMB-001 established the drug combination’s efficacy at doses which, when tested as monotherapy, had no effect.

Research and Information

A Phase 1 Single-and Multiple-Rising Dose Study of the Safety & PK of EMB-001, a Potential Treatment for Substance Use Disorders, Exploratory Efficacy Measures in Tobacco Use Disorder, Poster presentation, American Society of Clinical Psychopharmacology May 30-June 3  2016 Scottsdale, AZ

The Discovery and Development of EMB-001 for the Treatment of Substance Use Disorders, Poster presentation American Society for Experimental NeuroTherapeutics for its 19th Annual Meeting, March 17-19, 2016 Bethesda, MD

Effects of the combination of metyrapone and oxazepam on intravenous nicotine self-administration in rats
Goeders NE, Cohen A, Fox BS, Azar MR, George O, Koob, G, Psychopharmacology published online 2012 Mar 15

Effects of the combination of metyrapone and oxazepam on cocaine craving and cocaine taking: a double-blind, randomized, placebo-controlled pilot study
Kablinger AS, Lindner MA, Casso S, Hefti F, DeMuth G, Fox BS, McNair LA, McCarthy B, Goeders NE, J Psychopharmacol published online 11 January 2012, DOI: 10.1177/0269881111430745

Effects of the combination of metyrapone and oxazepam on cocaine and food self-administration in rats
Goeders NE, Guerin GF., Pharmacol Biochem Behav. 2008 Nov;91(1):181-9. Epub 2008 Jul 19

Combinations of oxazepam and metyrapone attenuate cocaine and methamphetamine cue reactivity.
Keller CM, Cornett EM, Guerin GF, Goeders NE., Drug Alcohol Depend. 2013 Dec 1;133(2):405-12. Epub 2013 Jul 26.

Stress, the hypothalamic-pituitary-adrenal axis, and vulnerability to drug abuse. (Please contact Embera for a copy of this article) Goeders NE, NIDA Res Monogr. 1998 Mar;169:83-104. Review. No abstract available. PMID: 9686412

Effects of surgical and pharmacological adrenalectomy on the initiation and maintenance of intravenous cocaine self-administration in rats.
Goeders NE, Guerin GF., Brain Res. 1996 May 25;722(1-2):145-52.

Stress and cocaine addiction.
Goeders NE,, J Pharmacol Exp Ther.2002 Jun;301(3):785-9. Review.PMID: 12023504

The HPA axis and cocaine reinforcement.
Goeders NE.,Psychoneuroendocrinology.2002 Jan-Feb;27(1-2):13-33. Review.PMID: 11750768

The impact of stress on addiction.
Goeders NE., Eur Neuropsychopharmacol.2003 Dec;13(6):435-41. Review. PMID: 14636959