Boehringer Ingelheim's Iclepertin Fails to Meet Endpoints in Phase III Schizophrenia Trials
Key Insights
Boehringer Ingelheim's iclepertin, a GlyT1 inhibitor, failed to demonstrate statistically significant benefits in improving cognitive function in schizophrenia (search) patients.
The Phase III CONNEX program, involving over 1,800 patients across 41 countries, did not meet primary or key secondary endpoints at six months.
As a result of the disappointing outcomes, Boehringer Ingelheim has discontinued the CONNEX-X long-term extension trial.
Boehringer Ingelheim's investigational drug, iclepertin, a glycine transporter 1 (GlyT1) inhibitor, has failed to meet its primary and key secondary endpoints in the Phase III CONNEX clinical program for cognitive impairment in adults with schizophrenia (search). The results indicate that iclepertin did not show statistically significant effects on cognition or functioning compared to placebo after six months of treatment.
The CONNEX program consisted of three randomized, double-blind, placebo-controlled trials (CONNEX-1, CONNEX-2, and CONNEX-3) that enrolled a total of 1,840 patients across 41 countries. Patients received 10 mg of oral iclepertin once daily over a 26-week period, in addition to their stable antipsychotic treatment. The primary endpoint was the change from baseline in the MATRICS Consensus Cognitive Battery (MCCB) overall composite T-score at six months. Secondary endpoints included changes from baseline in the Schizophrenia (search) Cognition Rating Scale, Virtual Reality Functional Capacity Assessment Tool, and Patient-Reported Experience of Cognitive Impairment in Schizophrenia total scores.
According to Boehringer Ingelheim, all three trials demonstrated that iclepertin was generally well-tolerated, with a safety profile consistent with previous studies. However, due to the lack of efficacy, the company has decided to discontinue the long-term extension trial, CONNEX-X, effective immediately.
"While these findings are disappointing, we remain dedicated to finding effective solutions for those living with serious mental illnesses," said Shashank Deshpande, Member of the Board of Managing Directors and Head of Human Pharma at Boehringer Ingelheim. "Our innovative pipeline includes over 20 additional investigative therapies in all stages of development and in different disease areas including schizophrenia (search) and major depressive disorder."
Schizophrenia (search) affects approximately 24 million people worldwide, with cognitive impairment being a core symptom affecting over 80% of individuals with the condition. This impairment significantly impacts problem-solving abilities, attention, memory, and overall daily functioning. Currently, there are no approved targeted pharmaceutical treatments for cognitive impairment in schizophrenia, representing a significant unmet medical need.
Iclepertin (BI 425809) was being investigated as a potential treatment to address this unmet need. It is an oral inhibitor of glycine transporter 1 (GlyT1), which regulates the concentration of glycine in the brain and modulates the activity of NMDA receptors for the neurotransmitter glutamate. Full efficacy and safety data from the CONNEX program will be submitted for presentation at an upcoming medical meeting, according to Boehringer Ingelheim.