Boehringer Ingelheim GmbH

02/09/2018 | Press release | Distributed by Public on 02/09/2018 17:53

Boehringer Ingelheim refocuses PDE9 inhibition brain research on schizophrenia following results from Phase II Alzheimer’s trials

Ingelheim, Germany, 09. February, 2018 - Boehringer Ingelheim today announced that their Phase II Alzheimer's disease trials with investigational compound BI 409306 had not met their efficacy endpoints and plans for further trials with BI 409306 in AD will therefore not be pursued. Instead, the company will refocus efforts on the ongoing schizophrenia trials with this compound.

These Alzheimer's disease trials were part of an extensive clinical trial programme exploring the efficacy of compounds which target malfunctioning of specific (glutamatergic) brain circuits as potential new treatments for specific symptoms and traits of a mental illness. As such, the investigational compound BI 409306 was explored in patients with cognitive impairment and those with memory dysfunction in schizophrenia and in Alzheimer's disease. Further investigations will focus on two studies in schizophrenia, aimed at prevention of relapse and at prevention of occurrence of a first psychotic episode.

Boehringer Ingelheim's continued engagement in the dementia field is confirmed by the planned phase II trials investigating another compound, BI 425809, a GlyT1 inhibitor, in a range of central nervous system indications which also include Alzheimer's disease.

'We recognise the immense anticipation around any progress in brain research that brings us closer to finding solutions for the many millions of people living with dementia. However, this is what research is about: disappointments are a daily experience in science, but even these clinical trial results will add to the understanding of brain function and contribute to future progress in this area.' said Dr Jan Poth, Therapeutic Area Head CNS and Immunology at Boehringer Ingelheim.

'Starting from our systematic neurobiological approach to CNS research, we will continue to build innovative approaches in our clinical trials and help advance the field in collaboration with the wider scientific community. We won't rest.' added Stephane Pollentier, Therapeutic Area Head Medicine CNS at Boehringer Ingelheim.

Following a comprehensive review of the complete trial data, Boehringer Ingelheim intends to present the full results at the Alzheimer's Association International Conference (AAIC) 2018 in July this year.

Mental illness remains one of the greatest health, social and economic challenges of our time and despite intensive efforts over many years, there is still no cure for Alzheimer's and little in the way of treatments (see also www.ep-ad.org(link is external)). As supporters of the 'We won't rest(link is external) ' - initiative from European Federation of Pharmaceutical Industries and Associations (EFPIA), Boehringer Ingelheim is determined to progress a deeper understanding of the brain pathways impacting mental illness. The recent Phase II trial results will add to the body of evidence and help refine CNS clinical trial programmes in the future.

NOTES TO EDITORS

BI 409306 Phase II in Alzheimer's disease Study Overview

  • BI 409306 was investigated in two studies (NCT02240693 and NCT02337907) designed to show superiority of BI 409306 over placebo in cognition. Topline data were pooled for analysis.
  • Further analysis will be needed to fully understand the results and how best to shape future research in Alzheimer's disease.
  • Phase II 12-week placebo controlled trials in Alzheimer's disease enrolled 457 participants in total.
  • The aim of the trials was to investigate the efficacy, safety and tolerability of BI 409306 compared to placebo given for 12 weeks in patients with cognitive impairment due to Alzheimer's disease.
  • BI 409306 blocks the action of a protein called phosphodiesterase 9A (PDE 9A). Blocking the action of PDE 9A improves signaling in certain parts of the brain, i.e. in the glutamatergic circuit of the brain. These pathways are thought to effect brain functions that are important to memory and learning.

Body of evidence

  • In 2017 the number of people believed to be living with some form of dementia is 50 million. This number will double almost every 20 years, reaching 75 million by 2030 and 131.5 million by 2050
  • Mental illness is one of the biggest health, social and economic challenges of our time. The number of people with mental illness continues to grow, while the treatments and the delivery of services remain inadequate
  • Traditional research approaches for mental illness have not delivered sufficient solutions that truly improve people's lives.
  • Cognitive impairment is one of a number of symptoms in mental illness that Boehringer Ingelheim is investigating by applying a systematic neurobiological approach to address these symptoms that goes beyond current disease classification

About BI 409306

BI 409306 is a potent and selective phosphodiesterase E9 (PDE9) inhibitor that targets the glutamatergic signaling pathways in the brain to increase synaptic strength and plasticity. These pathways are malfunctioning in schizophrenia and considered to be the pathophysiological basis of its positive, negative and cognitive symptoms.9,10 Dopaminergic pathways, which are also malfunctioning in schizophrenia, are understood to cause the psychotic exacerbations characteristic of relapse. Due to the functional interaction of the dopaminergic with the glutamatergic system in the pathophysiology of schizophrenia, it is conceivable that PDE9 inhibition might present an approach for prevention or reduction of symptomatic relapse.

About relapse in schizophrenia

Schizophrenia is a chronic, severe, and disabling brain disorder that may be caused by a combination of neurobiological and environmental factors. It affects about one percent of the world´s general population and occurs in men and women equally and at similar rates in all ethnic groups around the world. The onset of schizophrenia typically begins in early adulthood, but an individual may be diagnosed at any age.3

The symptoms of schizophrenia fall into three broad categories: positive symptoms (e.g., delusions, hallucinations, disordered thoughts), negative symptoms (e.g., restricted mood and drive), and cognitive symptoms (e.g., poor executive functioning, trouble focusing or paying attention, and the impairment of working memory, verbal and visual learning, and visual spatial memory). All of these significantly impact daily living.3

Existing treatment options for schizophrenia are primarily efficacious in treating positive symptoms and have limited, if any, efficacy for the prevention of relapse. Currently no specific therapy exists for the prevention of psychotic relapse in patients with schizophrenia, despite its high frequency. In subjects presenting with first-episode schizophrenia, relapse rates exceed 80% within five years4, and relapse itself represents an important predictor of subsequent deterioration approximately tripling healthcare costs in the year following.5 Further, multiple relapses have been associated with poorer long-term outcomes.6-8

About prevention of a first episode of psychosis in schizophrenia

'Psychosis' is a clinical term that refers to a loss of contact with reality, in which people have trouble distinguishing between what is real and what is not. Approximately three out of every 100 people will experience a psychotic episode in their lifetimes. Psychosis usually first appears in a person's late teens or early twenties. It occurs in men and women and across all cultures and socioeconomic groups.9 Psychosis is a symptom of several mental disorders, including schizophrenia.

A first episode of psychosis is often very frightening, confusing and distressing, particularly because it is an unfamiliar experience. Unfortunately, there are also many negative stereotypes and misconceptions associated with psychosis that can further add to a person's distress.9

Research suggests that the earlier the first episode of psychosis is diagnosed and treated, the more effective treatment outcomes and recovery will be. However, eight in ten patients receiving existing pharmacological therapy for schizophrenia do not achieve symptom remission in three months or more.10 Many of the currently available medications for psychosis also have severe side effects, which makes adherence challenging.10 There is a clear medical need to research and develop more effective treatments to help aid the recovery process and prevent further episodes of psychosis for people with schizophrenia.

About Boehringer Ingelheim in CNS

Boehringer Ingelheim

Innovative medicines for people and animals have for more than 130 years been what the research-driven pharmaceutical company Boehringer Ingelheim stands for. Boehringer Ingelheim is one of the pharmaceutical industry's top 20 companies and to this day remains family-owned. Day by day, some 50,000 employees create value through innovation for the three business areas human pharmaceuticals, animal health and biopharmaceutical contract manufacturing. In 2016, Boehringer Ingelheim achieved net sales of around 15.9 billion euros. With more than three billion euros, R&D expenditure corresponds to 19.6 per cent of net sales.

Social responsibility comes naturally to Boehringer Ingelheim. That is why the company is involved in social projects such as the 'Making More Health' initiative. Boehringer Ingelheim also actively promotes workforce diversity and benefits from its employees' different experiences and skills. Furthermore, the focus is on environmental protection and sustainability in everything the company does.

Intended audiences

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.