News - Deuterium-Modified Seroxat / Paxil / Paroxetine

http://www.reuters.com/article/pressRelease/idUS93196+14-Sep-2009+BW20090914

Phase I Results Presented at American College of Clinical Pharmacology


SAN ANTONIO--(Business Wire)--

Concert Pharmaceuticals, Inc. announced today the presentation of Phase 1 data

on CTP-347, a deuterium-modified analog of paroxetine for the treatment of hot

flashes. Concert presented the results during a poster session at the American

College of Clinical Pharmacology`s 38th Annual Meeting. This presentation

highlighted that subjects treated with CTP-347 substantially retained cytochrome

P450 2D6 (CYP2D6) enzyme activity. This enzyme is necessary for the metabolism

of many common drugs, but is irreversibly inactivated by a metabolite of

paroxetine, causing significant drug-drug interactions. Concert believes these

findings represent the first reported clinical data demonstrating that deuterium

substitution can alter a drug`s metabolism to reduce the potential for drug-drug

interactions in humans.



"This proof-of-concept study, combined with our preclinical findings,

demonstrates how we can apply deuterium chemistry to a proven drug to suppress

formation of an undesirable metabolite, while retaining the drug`s beneficial

pharmacologic activity," said Roger Tung, Ph.D., President and Chief Executive

Officer. "These are exciting results and provide one example of how our

deuterium chemistry platform can leverage proven drugs to create highly

differentiated yet risk-reduced new medicines."



The Phase 1 clinical trial was a randomized, single-blind, placebo-controlled,

ascending single- and multiple-dose study in 94 healthy volunteers. The primary

objective of the study was to evaluate the safety, tolerability and

pharmacokinetics of CTP-347. In this trial, CTP-347 was well-tolerated at all

doses evaluated and there were no clinically significant adverse events

reported. The most common adverse events were typical of selective serotonin

reuptake inhibitors (SSRIs) including headache, nausea and dizziness. In vitro

studies have previously shown that CTP-347, unlike paroxetine, does not exhibit

mechanism-based inactivation of CYP2D6 in human liver microsomes. The

pharmacokinetics of CTP-347 were consistent with those observed in preclinical

studies.



CTP-347 is a new chemical entity developed from Concert`s deuterium chemistry

platform by replacing key hydrogen atoms of paroxetine with deuterium as a

non-hormonal treatment for vasomotor symptoms (VMS) or hot flashes. Paroxetine

has been shown to be an effective treatment for VMS. However, it is a potent and

irreversible inactivator of CYP2D6 (cytochrome P450 2D6), a key liver enzyme

responsible for the metabolism of many commonly-prescribed drugs. Currently,

there is no FDA-approved non-hormonal treatment for VMS, a serious and sometimes

long-term condition associated with a range of undesirable effects including

depression, insomnia and lost productivity. Hormone replacement therapy can

effectively treat VMS. However, patients who currently or previously have been

treated for cancers of the breast or ovary, or who have a familial history of

these cancers, are often advised to avoid hormonal treatment. A non-hormonal

therapy may also be preferred by women who experience VMS following menopause in

whom hormone therapy is contraindicated or who have concerns about long-term

health risks posed by hormone replacement therapy.



About Deuterium



Deuterium is a safe, non-radioactive relative of hydrogen that can be isolated

from sea water and has been used extensively in human metabolic and clinical

studies. Since deuterium resembles hydrogen, deuterium-containing compounds are

expected to preserve the pharmacological activity of their hydrogen analogs. An

important difference is that deuterium is heavier than hydrogen and therefore

forms a stronger chemical bond to a carbon atom of a drug. The stronger chemical

bond obtained by selective deuterium modification in select instances may

substantially improve the drug`s metabolic properties, potentially resulting in

better safety, tolerability and/or efficacy.



About Concert



Concert Pharmaceuticals is a clinical stage biotechnology company focused on the

application of deuterium chemistry to create novel small molecule drugs.

Concert`s approach leverages known activity and safety of existing drugs to

reduce time, risk and expense of drug research and development. The Company has

a broad research pipeline encompassing many therapeutic areas including

infectious disease and renal disease, among others. Its lead development

candidate is the HIV protease inhibitor CTP-518. In 2009, Concert entered into a

potential $1 billion collaboration with GlaxoSmithKline to develop certain

deuterium-containing medicines. Founded in 2006, Concert has raised more than

$110 million of venture and institutional capital. For more information on

Concert Pharmaceuticals, please visit www.concertpharma.com.