Experimental Drug Fails in Alzheimer's Disease Trial

An investigational PDE9A inhibitor did not show efficacy in patients with Alzheimer’s disease.

Boehringer Ingelheim recently announced the results of a phase 2 trial in which an investigational Alzheimer’s disease (AD) drug did not meet its primary efficacy endpoint. Due to these findings, the manufacturer will not pursue further trials of BI 409306 for AD, according to a company press release.

However, the manufacturer still plans to pursue the compound as a treatment for schizophrenia.

“We recognize 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,” said Jan Poth, PhD, therapeutic area head of Central Nervous System (CNS) Diseases, Boehringer. “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.”

BI 409306 is a selective phosphodiesterase E9A inhibitor that acts on the glutamatergic signaling pathways in the brain, which increase synaptic strength and plasticity, according to the release. When malfunctioning, these signaling pathways can result in negative cognitive symptoms.

The AD trials were included in a clinical trial program that is exploring the efficacy of targeting glutamatergic brain pathways as a potential treatment for mental illness. The goal of the trial was to explore the efficacy, safety, and tolerability of BI 409306 over 12 weeks compared with placebo in 457 patients with AD.

Specifically, BI 409306 was investigated as a therapy to address cognitive impairment and memory dysfunction in patients with schizophrenia or AD.

Going forward, the drug will only be studied in patients with schizophrenia with goals of preventing relapse and the occurrence of a first psychotic episode, according to the release.

Boehringer is also exploring the efficacy of a ClyT1 inhibitor in CNS conditions, including AD.

“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,” said Stephane Pollentier, head of medicine therapeutic area CNS, Boehringer.