Results, Setbacks

Scientists toss another Alzheimer’s program into the scrap heap as PhII fails

While a legion of scientists have been employed in failed attempts to clear away the toxic tangles of proteins often found in the brains of Alzheimer’s patients, another set have continued to plug away at the various chemicals that play a role in orchestrating the brain’s complex cellular communications system.

But that’s proved just as frustrating.

Jan Poth

Today, Boehringer Ingelheim threw in the towel on an Alzheimer’s program for a drug called BI 409306, another effort to see if they could do a better job in modulating glutamate, one of those neurotransmitters that can run amuck in dementia.

The drug works by blocking a protein called PDE 9A which they believed would enhance cell signaling in the glutamatergic command center in the brain. Researchers recruited 457 patients for two studies, but like everything else that’s been put to a definitive test in the past 15 years, it failed to beat a placebo in improving cognition.

It’s a logical field to explore. Namenda was approved by the FDA 15 years ago after it was brought in from Europe, where it had been used for years. That’s a glutamatergic drug, focusing on the NMDA receptor — a big player in depression. The drug temporarily modulates cognitive symptoms of a disease that gradually wipes out memories.

Boehringer hasn’t given up on the drug. It has plans to test it in schizophrenia. And there’s a GlyT1 inhibitor — another glutamate drug called BI 425809 — which is being tested in Alzheimer’s and other CNS diseases.

The failure rate for Alzheimer’s drug has been running particularly hot of late. We recently got a close look at just how badly Eli Lilly’s solanezumab failed to alter the course of the disease by focusing on amyloid beta. Axovant cratered after back-to-back failures on a 5HT6 drug, another symptomatic effort focused on a key neurotransmitter. And Pfizer capped off the string of setbacks by calling it quits in the field, wiping out a pipeline of drugs and laying off 300 people working in the area.

Big players like Biogen, though, continue to invest heavily, convinced that they can succeed where all others failed. And an upstart like Denali can pull off a record-setting IPO by promising to pursue new strategies.

But the odds in this field are particularly tough, in an industry where failure is a daily reality.

“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 Jan Poth, therapeutic area head of CNS and immunology at Boehringer Ingelheim.


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