Concert Pharmaceuticals Initiates Phase 1 Single-Ascending Dose Trial of CTP-692 as an Adjunctive Treatment for Schizophrenia
“For decades all approved schizophrenia drugs have acted predominantly
by modulation of dopamine, or dopamine and serotonin receptors. By
activating glutamatergic pathways as an NMDA co-agonist, CTP-692 has the
potential to be a safe and effective new adjunctive treatment for
schizophrenia, and treat positive and negative symptoms and cognitive
The initial Phase 1 trial evaluated the safety, tolerability, and
pharmacokinetics of a single oral dose of CTP-692 versus D-serine in a
crossover study conducted in
The CTP-692 clinical program is supported by Concert’s preclinical
studies which have shown the potential of CTP-692 to improve upon the
safety profile of D-serine. D-Serine has been shown to cause
nephrotoxicity in published preclinical studies. Concert’s preclinical
studies have demonstrated that selective deuterium modification resulted
in increased exposure of CTP-692 relative to a similar dose of D-serine,
and administration of CTP-692 did not cause changes in serum creatinine
and blood urea nitrogen at doses where D-serine caused substantial
nephrotoxicity as assessed by these kidney function markers. These
preclinical results were presented by Concert at the
CTP-692 is a deuterium-modified analog of endogenous D-serine. Based on documented effects of D-serine, the Company believes that CTP-692 has the potential to restore NMDA receptor activity in key areas of the brain and improve clinical outcomes in patients with schizophrenia. CTP-692 has been shown to have similar ability to bind to and activate human NMDA receptors relative to D-serine, with the potential for an improved safety profile and improved clinical outcomes in the treatment of schizophrenia. CTP-692 will be developed as an adjunctive therapy administered in addition to standard antipsychotic medicines to improve both positive and negative symptoms as well as cognitive function in patients with schizophrenia.
An extensive body of evidence supports NMDA receptor hypofunction as a key underlying mechanism of schizophrenia. The NMDA receptor comprises two binding domains and, in addition to requiring glutamate binding, activation with a co-agonist such as D-serine or glycine is necessary for NMDA receptor activation. D-Serine is believed to be the most important human NMDA synaptic co-agonist. It has been postulated for some time that administration of NMDA co-agonists could benefit patients with schizophrenia since there is evidence that plasma and cerebrospinal fluid (CSF) levels of endogenous D-serine are reduced in patients with schizophrenia.
Schizophrenia is a chronic and devastating neuropsychiatric disorder that is ranked as a leading cause of disability worldwide. The disease afflicts nearly 1% of the world’s population, affecting both men and women equally, and striking all ethnic and socioeconomic groups with a similar level of prevalence. The illness is characterized by multiple symptoms that are categorized into three main clusters known as positive symptoms (hallucinations, delusional behaviors and thought disorder), negative symptoms (social withdrawal, flattened affect and poverty of speech), and cognitive dysfunction (diminished capacity for attention, working memory and executive function). The underlying basis of the current antipsychotic therapy is that excessive dopaminergic neurotransmission and dysfunctional D2 receptor signaling play key pathophysiological roles in the disease, and consequently all typical and atypical antipsychotics in clinical practice possess some level of D2 antagonist activity. Currently available antipsychotic drugs offer some benefit for positive symptoms but many patients are not adequately treated since currently available treatments are limited in their capacity to treat negative symptoms and cognitive dysfunction which are related to poor functional outcomes.
Cautionary Note on Forward Looking Statements
Any statements in this press release about our future expectations, plans and prospects, including statements about the clinical development of CTP-692 and other statements containing the words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “would,” and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: the uncertainties inherent in the initiation of future clinical trials, availability and timing of data from ongoing and future clinical trials and the results of such trials, whether preliminary results from a clinical trial will be predictive of the final results of that trial or whether results of early clinical trials will be indicative of the results of later clinical trials, expectations for regulatory approvals and other factors discussed in the “Risk Factors” section of our most recent Quarterly Report on Form 10-Q filed with the
Justine Koenigsberg (investors)
Concert Pharmaceuticals, Inc.
Kathryn Morris (media)
The Yates Network