Concert Pharmaceuticals, Inc. Presents Preclinical Data for Novel GABAA Subtype-Selective Modulator at NeuroScience 2011
Published: Nov 14, 2011
“C-21191 is a promising lead candidate with the potential for an improved side effect profile compared to existing non-selective GABA modulators such as benzodiazepines,” said Roger Tung, Ph.D., President and Chief Executive Officer of Concert Pharmaceuticals. “Our results demonstrate that C-21191 has strong preclinical efficacy in a number of relevant models and could represent an improvement over existing therapies for the treatment of a number of important indications.”
C-21191 is based on the preclinical compound L-838417 that was discovered and extensively profiled in preclinical efficacy models by Merck & Co. L-838417 is a subtype-selective GABAA receptor modulator designed to preserve GABA-related efficacy while minimizing the sedative, ataxic and dependency effects commonly seen with non-selective, full-agonist benzodiazepines. In preclinical models, L-838417 displayed strong muscle relaxant activity and efficacy against both inflammatory and neuropathic pain at doses that did not result in adverse effects. Despite its attractive pharmacological profile, L-838417 had demonstrated substantial pharmacokinetic limitations and its development was halted prior to clinical testing.
Through selective deuterium incorporation, C-21191 was identified by Concert as a new chemical entity that has demonstrated significantly improved pharmacokinetic characteristics in preclinical studies compared to L-838417. In side-by-side studies, C-21191 shows the same biochemical profile as L-838417. However, C-21191 demonstrated a three-fold increase in exposure compared to L-838417 in preclinical species. This improved pharmacokinetic profile resulted in a prolongation of exposure and a corresponding extension of the pharmacodynamic effects. C-21191 also demonstrated equivalent efficacy to gabapentin in a neuropathic pain model, with a superior duration of effect, at doses which did not cause sedation/ataxia in a rotarod model. The increased metabolic stability and duration of effect observed with C-21191 in these models support the potential of this compound as a therapeutic agent for treatment of spasticity and neuropathic pain, among several GABA-related CNS diseases, while avoiding significant sedation and ataxia liabilities.
About Spasticity and Pain
Spasticity is a debilitating symptom associated with neurological disorders including multiple sclerosis, stroke, spinal cord injury and cerebral palsy. The most commonly prescribed therapies for spasticity are limited in efficacy and are associated with significant dose-limiting side effects including drowsiness, fatigue and cognitive impairment, resulting in high rates of therapy discontinuations. According to the patient advocacy group for movement disorders, We Move, fewer than 50% of patients with spasticity are adequately managed with current treatments.
Neuropathic pain, a specific type of chronic pain, results from dysfunction of the peripheral or central nervous system. It is associated with a variety of etiologies, including multiple sclerosis, spinal cord injuries, trauma, infection, diabetes, immune deficiencies, ischemic disorders, and toxic neuropathies. Other causes include post-stroke pain, HIV-associated pain, herpes virus infection and cancer. According to Decision Resources, more than 5 million people in the US are affected by neuropathic pain.
About Deuterium Modification
Concert Pharmaceuticals specializes in the use of precision deuterium chemistry to create new chemical entities (NCEs) with unique properties based on known, pharmacologically active compounds. By selectively replacing one or more hydrogen atoms with deuterium, a stable and non-radioactive isotope of hydrogen, the company has been able to effect significant changes to the absorption, distribution, metabolism, or excretion (ADME) profile of a number of compounds with the potential for improvements in safety, tolerability, and/or efficacy.
Concert Pharmaceuticals is a clinical stage biotechnology company focused on applying the company’s DCE Platform™ (deuterated chemical entity platform) to create novel and differentiated small molecule drugs. Concert’s approach leverages decades of pharmaceutical and clinical experience to reduce the time, risk and expense needed to create important new medicines. The company has a broad research pipeline encompassing many therapeutic areas including antiviral disease, renal disease, and CNS disorders, among others. 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.
Concert Pharmaceuticals, the CoNCERT logo and the DCE Platform are trademarks of Concert Pharmaceuticals, Inc.
Contact:. Concert Pharmaceuticals, Inc. Justine E. Koenigsberg, 781-674-5284 (Investors) or The Yates Network Kathryn Morris, 845-635-9828 (Media).