Boehringer provides update on iclepertin Phase III program in schizophrenia

Boehringer Ingelheim today announced top-line results from the Phase III CONNEX clinical program in cognitive impairment in adults with schizophrenia, showing primary and key secondary endpoints were not met.^1–6 Overall, no statistically significant effects on cognition or functioning were observed in patients treated with iclepertin versus placebo at six months.¹ All three trials demonstrated that iclepertin, a glycine transporter 1 (GlyT1) inhibitor, was generally well tolerated, with a safety profile that remains consistent with previous studies.^1,2,7

“While these findings are disappointing, we remain dedicated to finding effective solutions for those living with serious mental illnesses. 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,” said Shashank Deshpande, Member of the Board of Managing Directors and Head of Human Pharma at Boehringer Ingelheim. “In the near future more can be expected. Our gratitude goes to the patients and clinical investigators whose time and commitment made this research possible.”  

CONNEX was the largest program for cognitive impairment in schizophrenia to date. Boehringer believes that the results will aid scientific understanding and inform future research for patients living with cognitive impairment in schizophrenia, an area of high unmet need with no approved targeted pharmaceutical treatment options available.^8,9 Full efficacy and safety data will be submitted for presentation at an upcoming medical meeting. 

About cognitive impairment in schizophrenia 

Schizophrenia affects approximately 24 million people worldwide.¹⁰ Cognitive impairment is one of the three core symptom domains of schizophrenia, along with positive and negative symptoms.¹¹ Cognitive impairment affects more than 80% of people with this condition, manifesting early in patients’ lives, and representing a leading cause of disability and impairment in daily functioning.^8,9,12 People with schizophrenia often face cognitive challenges that impact their problem-solving abilities, attention and memory.^8,9 These problems can make it difficult to live an independent and productive life.^8,9 They can also cause a person to struggle with simple tasks such as attending appointments, which can make treatment difficult.^8,9 

There are no approved targeted pharmaceutical treatments for cognitive impairment in schizophrenia.^8,9

About iclepertin and the CONNEX clinical program 

Iclepertin (BI 425809), an investigational oral inhibitor of glycine transporter 1 (GlyT1), was studied as a potential treatment for cognitive impairment in adults with schizophrenia.^1–6 Iclepertin has not been approved by any regulatory authorities.  

CONNEX was a Phase III clinical program designed to assess the safety and efficacy of iclepertin for improving cognitive impairment in adults with schizophrenia.^2–6 The program comprised three clinical trials, all of which were randomized, double-blind, placebo-controlled parallel group trials investigating treatment with oral iclepertin 10 mg once daily over a 26-week period in adults with schizophrenia who received stable antipsychotic treatment.^2–6 The CONNEX clinical program enrolled 1,840 patients in 41 countries.^4–6  

Boehringer Ingelheim decided to discontinue the long-term extension trial, CONNEX-X, effective immediately.¹³

Boehringer Ingelheim

Boehringer Ingelheim is a biopharmaceutical company active in both human and animal health. As one of the industry’s top investors in Research and Development, the company focuses on developing innovative therapies in areas of high unmet medical need. Independent since its foundation in 1885, Boehringer takes a long-term perspective, embedding sustainability along the entire value chain. More than 53,500 employees serve over 130 markets to build a healthier, more sustainable, and equitable tomorrow. Learn more at https://www.boehringer-ingelheim.com. 

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This press release is issued from our Corporate Headquarters in Ingelheim, Germany and is intended to provide information about our global business. Please be aware that information relating to the approval status and labels of approved products may vary from country to country, and a country-specific press release on this topic may have been issued in the countries where we do business. 

References: 

1. Boehringer Ingelheim. Data on File. 
2. Rosenbrock H, Desch M, Wunderlich G. Development of the novel GlyT1 inhibitor, iclepertin (BI 425809), for the treatment of cognitive impairment associated with schizophrenia. Eur Arch Psychiatry Clin Neurosci. 2023;273(7):1557–1566. doi:10.1007/s00406-023-01576-z. 
3. Falkai P, Reuteman-Fowler C, Blahova Z, Ikezawa S, Marder SR, Krystal JH. Efficacy and safety of iclepertin (BI 425809) in patients with schizophrenia: CONNEX, a Phase III randomised controlled trial programme. Eur Psychiatry. 2023;66(Suppl 1):S637. doi:10.1192/j.eurpsy.2023.1325. 
4. ClinicalTrials.gov. NCT04846868. Clinical Trial of Iclepertin Effect on Cognition and Functional Capacity in Schizophrenia (CONNEX-1). Available from: https://clinicaltrials.gov/study/NCT04846868. Accessed January 2025. 
5. ClinicalTrials.gov. NCT04846881. Clinical Trial of Iclepertin Effect on Cognition and Functional Capacity in Schizophrenia (CONNEX-2). Available from: https://clinicaltrials.gov/study/NCT04846881. Accessed January 2025. 
6. ClinicalTrials.gov. NCT04860830. CONNEX-3: A Study to Test Whether Iclepertin Improves Learning and Memory in People With Schizophrenia. Available from: https://clinicaltrials.gov/study/NCT04860830. Accessed January 2025. 
7. Fleischhacker WW, Podhorna J, Gröschl M, et al. Efficacy and safety of the novel glycine transporter inhibitor BI 425809 once daily in patients with schizophrenia: a double-blind, randomised, placebo-controlled phase 2 study. Lancet Psychiatry. 2021;8(3):191–201. doi:10.1016/S2215-0366(20)30513-7. 
8. Kitchen H, Rofail D, Heron L, Sacco P. Cognitive impairment associated with schizophrenia: a review of the humanistic burden. Adv Ther. 2012;29(2):148–162. doi:10.1007/s12325-012-0001-4. 
9. Bowie CR, Harvey PD. Cognitive deficits and functional outcome in schizophrenia. Neuropsychiatr Dis Treat. 2006;2(4):531–536. doi:10.2147/nedt.2006.2.4.531. 
10. World Health Organization. Schizophrenia. Available from: https://www.who.int/news-room/fact-sheets/detail/schizophrenia. Accessed January 2025. 
11. Stahl SM. Stahl’s Essential Psychopharmacology. 4th ed. Cambridge University Press; 2013. 
12. Mosiołek A, Gierus J, Koweszko T, Szulc A. Cognitive impairment in schizophrenia across age groups: a case-control study. BMC Psychiatry. 2016;16:37. doi:10.1186/s12888-016-0749-1. 
13. ClinicalTrials.gov. NCT05211947. A Study to Test Long-term Safety of Iclepertin in People With Schizophrenia Who Took Part in a Previous CONNEX Study. Available from: https://clinicaltrials.gov/study/NCT05211947. Accessed January 2025.

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