Amgen and Novartis are stopping work on an experimental Alzheimer’s disease drug after an early look at clinical data showed worsening cognitive function in patients.
The interim results announced Thursday were part of a pre-planned review of data from two pivotal clinical trials testing the drug, umibecestat. Based on that review, Amgen (NASDAQ: AMGN) and Novartis (NYSE: NVS) said that they are discontinuing further development of the drug because its potential benefit does not outweigh the risks.
Umibecestat’s fate deals another blow to the hypothesis that Alzheimer’s can be treated by targeting the buildup of plaques of amyloid protein on the brain. Despite hundreds of millions of dollars spent on clinical trials enrolling tens of thousands of patients, all experimental therapies that target amyloid have failed so far. This year alone has seen two failures. In January, Roche and AC Immune (NASDAQ: ACIU) halted development of amyloid-busting drug crenezumab after an interim look at Phase 3 data. In March, Biogen (NASDAQ: BIIB) stopped late-stage tests of its drug aducanumab after an independent analysis concluded the studies would likely fail.
Umibecestat is slightly different than most of the other amyloid drugs that have failed in clinical trials. Rather than breaking up amyloid, the drug was developed to block beta secretase 1 (BACE1), an enzyme that plays a role in the formation of amyloid plaques. The hope was that this approach could prevent or delay the onset of Alzheimer’s. But so-called BACE inhibitors haven’t shown much success either. In 2017, development of verubecestat was halted after an independent assessment concluded the Merck (NYSE: MRK) BACE inhibitor would not work. Elenbecestat, an Eisai BACE inhibitor being developed in partnership with Biogen, is currently in late-stage testing. In March, an independent board recommended that two Phase 3 tests of the drug continue.
The Amgen and Novartis partnership on umibecestat dates to 2015, when the companies agreed to work together to develop new drugs for migraines and Alzheimer’s. In 2017, the Banner Alzheimer’s Institute joined the partnership. The partners planned a five-year study targeting an enrollment of approximately 2,000 patients from more than 20 countries. The trials enrolled patients at high risk of developing Alzheimer’s due to age and carrying either of two copies of apolipoprotein E (APOE) 4, a genetic mutation that puts patients at higher risk of developing the disease.
Amgen, Novartis, and Banner say they plan to further analyze the umibecestat clinical trials and present the data at a future scientific venue to contribute to the body of knowledge surrounding Alzheimer’s.