Cerevance’s CVN058 Achieves Primary Endpoint in Phase Ib Schizophrenia Cognition Study
- Category: Small Molecules
- Published on Tuesday, 17 November 2020 11:10
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Positive results with biomarker of cerebral cortical dysfunction raises hope for treatment of cognitive impairment associated with schizophrenia
BOSTON, MA, USA I November 16, 2020 I Cerevance, a private drug discovery and development company focused on brain diseases, today announced positive results from a Phase 1b clinical trial evaluating the company’s oral compound, CVN058, in a biomarker study evaluating its potential as a treatment for cognitive impairment associated with schizophrenia (CIAS).
“A single dose of CVN058 elicited a statistically significant improvement in mismatch negativity (MMN), an auditory evoked potential generated in the cerebral cortex that is typically impaired in schizophrenics,” noted David H. Margolin, M.D., Ph.D., senior vice president of clinical and translational medicine at Cerevance. “The normalization of MMN brainwaves, a biomarker of cortical dysfunction, leads us to believe our approach can potentially improve diverse aspects of cognition in schizophrenic patients.”
CVN058 is a novel, brain-penetrant, small-molecule antagonist of the type 3 receptor for serotonin, an important neurotransmitter. The Phase 1b, double-blind, placebo-controlled, three-period cross-over study evaluated CVN058 target engagement in the cerebral cortex by measuring mismatch negativity (MMN) as a pharmacodynamic marker.
Nineteen male and female subjects with schizophrenia or schizoaffective disorder, aged 18 to 50 years old, received a single oral dose of CVN058 (low-dose, 15 mg or 75 mg; high-dose, 150 mg) or matching placebo at each study visit. MMN and other cortical biomarkers were recorded in the hours after dosing. The sequence in which a subject took each of the three regimens was randomized, with a minimum of a seven-day washout between doses. These treatments had no serious or severe adverse effects.
The number of diagnosed prevalent cases of schizophrenia with comorbid cognitive impairment is expected to exceed 4 million in the seven major pharmaceutical markets in 2022. Cognitive impairment associated with schizophrenia (CIAS)—which may include deficits in attention, working memory and executive function—has a negative impact on patients’ quality of life and ability to function. Although cognitive symptoms in schizophrenia are well characterized, no formal diagnostic criteria exist. Furthermore, no pharmacological agents are approved to treat the condition, and no marketed therapy tested to date has established clear, meaningful efficacy, which underscores the difficulty of drug development in this arena and accentuates the need for proven treatment options.
“The cognitive impairment experienced by many patients with schizophrenia desperately needs an effective treatment,” said Daniel C. Javitt, M.D., Ph.D., lead investigator and a world-renowned researcher in the study of schizophrenia and cognition. Dr. Javitt directs the Schizophrenia Research Program at the Nathan S. Kline Institute for Psychiatric Research and is also Professor and Director of the Division of Experimental Therapeutics in the Department of Psychiatry and Neuroscience at Columbia University College of Physicians and Surgeons. “We are very encouraged by CVN058’s results in our MMN translational study and look forward to confirming its potential cognitive benefits in future clinical trials.”
Cerevance, a private, clinical-stage pharmaceutical company focused on brain diseases, is applying a new technology, called NETSseq, to reveal transcriptional and epigenetic differences between specific cell types in mature human brains. NETSseq profiles neuronal and glial cell populations at depths not possible with other approaches, generating unprecedented data sets and insights. The company has thus far partnered with 17 brain banks around the world to assemble a growing collection of more than 8,000 clinically annotated, human brain tissue samples from healthy and diseased donors spanning nine decades in age. By applying NETSseq to specific cell types critical to circuits disrupted by disease and comparing vulnerable and resilient cell populations, Cerevance’s scientists have begun identifying targets and advancing a pipeline of novel therapeutics that modulate them for CNS diseases.