Boehringer Ingelheim halts development of cognitive therapy for Schizophrenia

GERMANY – Boehringer Ingelheim’s ambitious effort to develop the first drug therapy targeting cognitive impairment in schizophrenia has faced a significant setback, leading to the termination of its program.

Early results from the phase 3 CONNEX clinical program, comprising three trials, revealed that the drug iclepertin, a glycine transporter 1 (GlyT1) inhibitor, failed to meet its primary endpoint.

Specifically, it showed no statistically significant improvement in the MATRICS Consensus Cognitive Battery overall composite T-score over six months, nor did it deliver positive results on secondary measures.

In light of these findings, Boehringer has decided to halt the associated long-term extension trial, CONNEX-X, effectively bringing an end to what the company described as the largest-ever program focused on cognitive impairment in schizophrenia.

More than 1,800 patients had been enrolled in this groundbreaking initiative. The setback is a major disappointment for patients, healthcare providers, and the company, as cognitive impairment is one of the core challenges of schizophrenia.

Alongside positive symptoms such as hallucinations and negative symptoms like social withdrawal, cognitive impairment severely impacts the lives of approximately 80% of the 24 million people worldwide living with schizophrenia.

This condition often prevents patients from managing basic tasks, including attending medical appointments, further complicating their care.

Iclepertin’s mechanism of action involved regulating glycine concentrations in the brain to modulate NMDA receptor activity for the neurotransmitter glutamate.

The drug had been a key focus for Boehringer, with the potential to address an unmet need in schizophrenia treatment.

Dr. Paola Casarosa, Boehringer’s head of innovation, had previously highlighted iclepertin and another mental health candidate—BI 1569912, a negative allosteric modulator (NAM) of NR2b—as pivotal to the company’s future growth and innovation in mental health therapies.

While iclepertin’s failure has effectively closed the chapter on Boehringer’s GlyT1 inhibitor program, the company continues to explore other avenues.

Its current pipeline includes a glutamate receptor modulator in early development and BI 1569912, which is undergoing phase 2 trials for major depressive disorder.

This drug is also being tested for borderline personality disorder and post-traumatic stress disorder (PTSD).

Additionally, Boehringer has been investing in innovative approaches, including a €670 million (US $691 million) deal with Sosei Heptares for GPR52 agonists, which aim to address positive, negative, and cognitive symptoms of schizophrenia by modulating glutamate and dopamine regulation.

Acknowledging the recent disappointment, Shashank Deshpande, Boehringer’s head of human pharma, emphasized the company’s continued commitment to mental health innovation.

“While these findings are disappointing, we remain dedicated to finding effective solutions for those living with serious mental illnesses,” he said in a statement.

He further highlighted that Boehringer’s pipeline includes over 20 investigative therapies across various stages of development, signaling hope for future breakthroughs in schizophrenia and other mental health conditions.