The Phase 3 clinical trial program, known as COGNITIV SZ, is designed to assess the safety and efficacy of encenicline compared to placebo as a pro-cognitive therapy in patients with schizophrenia treated with atypical antipsychotics.
Each of the two 26-week multinational trials enrolled more than 750 patients. Encenicline is a novel alpha 7 agonist in Phase 3 development by FORUM to treat cognitive impairment in schizophrenia and Alzheimer’s disease.
"Completing patient enrollment in the pivotal Phase 3 clinical trials for our lead product candidate encenicline in schizophrenia marks an exciting milestone for FORUM and in our vision to deliver innovative medicines to patients with serious brain disease," said Deborah Dunsire, M.D., President and Chief Executive Officer of FORUM Pharmaceuticals.
"In parallel with these trials, we continue advancing other candidates in our clinical pipeline. Patient enrollment is well underway in the COGNITIV AD trial program, which consists of two separate multinational Phase 3 clinical trials to investigate the use of encenicline in Alzheimer’s disease.
"In addition, our genetically-targeted drug candidate, FRM-0334, designed to treat the rare progranulin variant of frontotemporal dementia, recently progressed into proof of mechanism Phase 2 studies. This is an exciting time for FORUM and we look forward to sharing top-line results from the Phase 3 encenicline trials in schizophrenia in the first half of 2016."
"While treatment exists for positive symptoms, nearly all of the 2.2 million U.S. patients with schizophrenia also experience cognitive impairment and negative symptoms, for which there currently is no approved treatment available," said Steven G. Potkin, M.D., Professor of Psychiatry, Psychiatry and Human Behavior School of Medicine, University of California, Irvine, and an investigator in the COGNITIV SZ trials.
"The degree to which patients experience cognitive impairment is strongly associated with more limited real world functioning, impacting their activities of daily living, their social interactions, relationships and their ability to work and live independently. A treatment that addresses these needs could potentially enable patients to experience better school or work performance, increase their likelihood of living independently, have a better quality of life and improve adherence to medication and reduce relapse rates."
"Results from two prior FORUM studies in more than 300 patients with schizophrenia indicated that encenicline was associated with statistically significant and clinically meaningful improvements in cognitive function, negative symptoms and clinical function," said Dana C. Hilt, M.D., Senior Vice President, Clinical Development and Chief Medical Officer of FORUM.
"Encenicline is the first drug to reach Phase 3 studies in this indication. These studies are designed to build on the robust results from our Phase 2 trials, to develop a pro-cognitive therapeutic that can potentially address cognitive impairment and negative symptoms for people with schizophrenia, and that can be administered with current antipsychotic therapy, which is the standard of care to treat positive symptoms of the disease."
The COGNITIV SZ Phase 3 clinical trial program includes two randomized, double-blind, placebo-controlled studies evaluating the safety and efficacy of two oral doses of once daily treatment with encenicline as a pro-cognitive treatment compared to placebo when added to atypical antipsychotic therapy in people with schizophrenia.
Primary endpoints of the trials include effect on cognitive function as measured by the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) overall neurocognitive index, and effect on clinical function as measured by the interview-based Schizophrenia Cognition Rating Scale (SCoRS).
Secondary endpoints of the trial include the clinical efficacy as measured by the negative subscale of the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression – Severity (CGI-S), Clinical Global Impression – Change scale (CGI-C), and quality of life, using the EuroQoL-5D (EQ-5D). Safety will be determined by clinical and laboratory safety assessments. The two global 26-week trials each enrolled more than 750 patients at a total of approximately 200 clinical sites.
Encenicline is a novel, orally administered, highly brain-penetrant, selective, and potent agonist of the alpha 7 receptor found in hippocampal and cortical neurons involved in cognition. Encenicline is believed to work in low concentrations to prime the alpha 7 receptor to increase its response to acetylcholine, a naturally occurring neurotransmitter.
This effect is thought to activate brain networks associated with sensory gating, attention, and cognition – thus enhancing these networks for improved neural processing and improved cognitive performance in areas such as memory and executive function. Encenicline is in development by FORUM Pharmaceuticals as a long-term treatment to improve cognitive function with sustained effect in schizophrenia and Alzheimer’s disease.
In preclinical studies, encenicline increased neuronal synchronization and enhanced synaptic plasticity, measured by an increase in long term potentiation (LTP). These effects may be linked to enhanced cognition not only in Alzheimer’s disease and schizophrenia, but suggest potential in other diseases with cognitive impairment.