Concert Pharmaceuticals Initiates Phase 1 Clinical Program of CTP-692 for the Treatment of Schizophrenia
“Significant unmet need still exists to improve upon the existing
standard-of-care in schizophrenia and we believe CTP-692 has the
potential to act on a key mechanism not addressed today with currently
available agents. By enhancing NMDA receptor activity, CTP-692 offers
the promise of improved clinical outcomes for patients with
The Phase 1 program is expected to enroll approximately 80 healthy volunteers. Dosing has been initiated to assess the safety, tolerability, and pharmacokinetics of a single oral dose pharmacokinetic comparison of CTP-692 versus D-serine. Following successful completion of the crossover trial, Concert will assess the safety, tolerability, and pharmacokinetics of single-ascending oral doses of CTP-692 in a double-blind, placebo-controlled trial. The Phase 1 program will also assess multiple doses of CTP-692 dosed orally over several days in a double-blind, placebo-controlled, multiple-ascending dose trial.
The CTP-692 clinical program is supported by Concert’s preclinical
studies which have shown the potential for 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 resulted in no changes in serum creatinine
and blood urea nitrogen at doses where D-serine caused substantial
nephrotoxicity assessed by these kidney markers. These preclinical
results were presented by Concert at the
About CTP-692 and Schizophrenia
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 is expected to have similar pharmacology 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 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 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 exhibit efficacy for positive symptoms, but are limited in their capacity to treat negative symptoms and cognitive dysfunction which are related to poor functional outcomes for these patients.
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