The Banner Alzheimer’s Institute alongside Amgen and Novartis has decided to halt the trials of BACE1 inhibitor CNP520 (umibecestat). The decision comes after the drug led to the worsening of symptoms in some patients.
New Alzheimer’s drug fails
The new BACE1 drug led to the worsening of symptoms in trial participants at a much faster rate than placebo. Amgen and Novartis’ drug is the newest in a long line of abandoned projects in Alzheimer’s research. Two other big candidates that could have potentially given us a breakthrough were abandoned this year as well. One of them was crenezumab by AC Immune and Roche, and the second was aducanumab by Eisai and Biogen.
BACE inhibitor treatment is consistently proving to be a bad idea for Pharma companies as signs of cognitive decline accelerate when the drug is administered. Merck & Co., Janssen, and Lilly have also reported similar issues in their trials previously. The drug class is focused on beta-amyloid cleaving enzyme (BACE), which is crucial for the production of beta-amyloid peptides (Aβ). Pharma companies have been hoping that their BACE drugs may reduce the production of Aβ that could help in slowing down Alzheimer’s progress. Instead, it has shown the opposite effect.
What happened with the Amgen-Novartis drug?
The CNP520 was undergoing two pivotal phase 2/3 studies as part of the Alzheimer’s Prevention Generation Program. It was designed to prevent the delay in the onset of Alzheimer’s risk in people who have a high risk of developing this disease because of age and genetic factors.
The researchers at Novartis and Amgen were aware of the problems witnessed in similar trials, but they did not see any issues in their own early trials. They found an assessment of unblinded data while conducting a regular pre-planned review that highlighted the worsening of cognitive function due to the drug. The trials were suspended thereafter.
Amgen’s executive vice president of research and development David Reese commented on the discontinuation of trials, saying,
“Our team joins the millions whose lives are impacted by Alzheimer’s disease in our disappointment that the Generation Program did not yield a treatment for Alzheimer’s disease prevention.”
Several voices in the industry now call for underlining all drugs targeting BACE, and there is no dearth of novel modalities that could possibly help Alzheimer’s patients. However, Reese is still a believer. He said that Amgen still believes in a key role of amyloid in Alzheimer’s.