Biotie Announces Start of Clinical Study With Nepicastat (SYN117) in Cocaine Dependence

NEPICASTAT

TURKU, FINLAND–BIOTIE THERAPIES CORP. STOCK EXCHANGE RELEASE 10 May 2013 at 9.00 a.m.

Biotie announces start of clinical study with nepicastat (SYN117) in cocaine dependence

Biotie Therapies today announced the start of a Phase 2 clinical study evaluating nepicastat (SYN117) in cocaine dependence. The National Institute on Drug Abuse (NIDA) at the US National Institutes of Health is funding the conduct of the study under a Collaborative Research and Development Agreement (CRADA) signed in December 2011.

The study is a randomized, double-blind placebo-controlled 11-week trial and is expected to enroll about 180 treatment-seeking cocaine-dependent subjects. The study will be conducted at approximately 12 US clinics specializing in the treatment of drug dependence.

The trial is expected to take approximately two years to complete.

ABOUT NEPICASTAT (SYN117)

Nepicastat is an orally administered, potent and selective inhibitor of the enzyme dopamine beta-hydroxylase (DBH) which converts dopamine into norepinephrine. Like many other addictions, cocaine dependence is driven by dysregulation in the dopamine-reward system. Inhibition of DBH by nepicastat increases levels of dopamine, which may reduce craving for cocaine, and reduces the levels of norepinephrine, which may decrease the pleasurable responses to cocaine and the potential for stress-induced relapse following withdrawal. Biotie has previously conducted a placebo-controlled Phase 2a study in non-treatment seeking cocaine addicts. The study showed that nepicastat had a favourable safety profile and was well tolerated when administered with cocaine.

Nepicastat has also been evaluated as a potential treatment for post-traumatic stress disorder (PTSD). In December 2012, Biotie announced top-line data from an investigator-initiated Phase 2 study in PTSD. In this study, nepicastat was generally well tolerated but was not effective in relieving PTSD-associated symptoms when compared to placebo. Biotie is evaluating data from this study in further detail and will then decide on next steps with nepicastat in PTSD

Biotie holds full rights to nepicastat and will be able to use data from studies conducted with NIDA to support future potential regulatory submissions.

ABOUT BIOTIE

Biotie is a specialized drug development company focused on the development of drugs for neurodegenerative and psychiatric disorders (e.g. Parkinson’s disease, Alzheimer’s disease and other cognitive disorders, alcohol and drug dependence (addiction) and post-traumatic stress disorder), and inflammatory and fibrotic liver disease. The company has a strong and balanced development portfolio with several innovative small molecule and biological drug candidates at different stages of clinical development. Biotie’s products address diseases with high unmet medical need and significant market potential.

Biotie’s most advanced product, Selincro (nalmefene), licensed to H. Lundbeck A/S, has on 28 February 2013 received European marketing authorization for the reduction of alcohol consumption in adult patients with alcohol dependence who have a high level of alcohol consumption. In addition, Biotie has a strategic collaboration with UCB Pharma S.A. covering tozadenant which is transitioning into Phase 3 development for Parkinson’s disease. Biotie shares are listed on NASDAQ OMX Helsinki Ltd.

Nepicastat (INN, codenamed SYN117, RS-25560-197) is an inhibitor of dopamine beta-hydroxylase, an enzyme that catalyzes the conversion of dopamine to norepinephrine.^[1]

It has been studied as a possible treatment for congestive heart failure, and appears to be well tolerated as such.^[2] As of 2012, clinical trials to assess nepicastat as a treatment forpost-traumatic stress disorder (PTSD) and cocaine dependence have been completed.^[3][4]

Synthesis 

U.S. Patent 5,719,280

 

1.  Stanley WC, Li B, Bonhaus DW, et al. (August 1997). “Catecholamine modulatory effects of nepicastat (RS-25560-197), a novel, potent and selective inhibitor of dopamine-beta-hydroxylase”. Br J Pharmacol 121 (8): 1803–9. doi:10.1038/sj.bjp.0701315.PMC 1564872. PMID 9283721.
2. Hegde SS, Friday KF (December 1998). “Dopamine-beta-hydroxylase inhibition: a novel sympatho-modulatory approach for the treatment of congestive heart failure”. Current pharmaceutical design 4 (6): 469–79. PMID 10197057.
3.  “Pharmacogenetic Clinical Trial of Nepicastat for Post Traumatic Stress Disorder (PTSD)”. ClinicalTrials.gov. U.S. National Institutes of Health. June 4, 2008. Retrieved on February 1, 2012.
4.  “Study of Safety and Potential Efficacy of SYN117 in Cocaine Dependent Volunteers”. ClinicalTrials.gov. U.S. National Institutes of Health. August 15, 2008. Retrieved on February 1, 2012.