Boehringer drug for brain fog in schizophrenia fails trial
Boehringer Ingelheim's attempt to develop the first drug therapy for impaired cognitive function in schizophrenia, a core feature of the illness, has suffered what looks like a terminal setback.
The first results from the phase 3 CONNEX clinical programme, which encompasses three clinical trials, have shown that iclepertin – a glycine transporter 1 (GlyT1) inhibitor – was unable to show a statistically significant benefit on the primary endpoint, change from baseline in the MATRICS Consensus Cognitive Battery overall composite T-score at six months, as well as secondary measures.
As a result of the disappointing results, Boehringer said that it was abandoning a long-term extension trial called CONNEX-X, bringing to an end what it said was the largest programme for cognitive impairment in schizophrenia to date, enrolling more than 1,800 patients.
It's a major disappointment for the company, as well as patients and healthcare workers, as cognitive impairment ranks alongside positive symptoms like hallucinations and negative symptoms like apathy and social withdrawal among the debilitating consequences of schizophrenia.
Schizophrenia affects approximately 24 million people worldwide, and cognitive impairment is seen in around 80% of them, making it hard for them to carry out simple tasks – like attending appointments – that can complicate their care.
Iclepertin – which regulates the concentration of glycine in the brain and in turn modulates the activity of NMDA receptors for the neurotransmitter glutamate – was one of two mental health programmes singled out by Boehringer's head of innovation, Dr Paola Casarosa, at an R&D update last year as having the potential to make a major difference to patients and fuel the company's future growth.
The other was a negative allosteric modulator (NAM) of NR2b for mood disorders, codenamed BI 1569912, which is in phase 2 testing as a monotherapy and add-on to other antidepressants in major depressive disorder, and also in earlier-stage development for borderline personality disorder and post-traumatic stress disorder (PTSD).
Boehringer's most up-to-date pipeline listing does not mention any other potential indications for iclepertin or other GlyT1 inhibitors, although, it does mention a glutamate receptor modulator in early clinical development.
Last year, the privately-held pharma group licensed rights to a portfolio of GPR52 agonists from Sosei Heptares in a €670 million deal, saying at the time the drugs – which affect glutamate and dopamine regulation – have the potential to tackle positive, negative, and cognitive symptoms in schizophrenia.
"While these findings are disappointing, we remain dedicated to finding effective solutions for those living with serious mental illnesses," commented Shashank Deshpande, Boehringer's head of human pharma in a statement.
"Our innovative pipeline includes over 20 additional investigative therapies in all stages of development and in different disease areas including schizophrenia and major depressive disorder," he said, adding: "In the near future, more can be expected."
