By Bill Alpert
Roche Holding has one of the most promising treatments for Alzheimer's in clinical trials. The drug is several years away from reaching the market, however.
Amid a Madrid conference for Alzheimer's researchers, Roche scientists talked to investors about the company's experimental diagnostics and drugs for the devastating brain disease -- including trontinemab, the first anti-Alzheimer's antibody that easily crosses the blood-brain barrier.
Roche plans to start pivotal Phase 3 trials of the drug next year. They wouldn't be complete until 2028.
"The blood-brain barrier has been the Holy Grail of neuroscience therapeutics," said Azad Bonni, who heads Roche's neuroscience drug development. In a Phase 2 study of 160 patients, trontinemab has practically cleared most patients' brain cells of the deadly amyloid plaque that accumulates in Alzheimer's.
The brain's blood vessels present a barrier to large molecules such as antibodies, so the approved anti-amyloid drugs -- Eli Lilly's Kisunla and the Esai/ Biogen product Leqembi -- get little as 0.1% of their plaque-targeting antibodies into the brain.
GSK drew attention to blood-brain barrier technologies in Alzheimer's on Monday, with its announced acquisition of a privately held leader in the space, for $1.4 billion.
By tagging its antibody with a molecular key that unlocks the barrier, Roche's trontinemab quickly permeates the brain. The company calls the barrier-passing trick its BrainShuttle technology. It will try it later with treatments for other brain disorders.
As a result, the Roche antibody is clearing amyloid faster than the approved drugs, yet with much lower doses. That has resulted in relatively few serious side effects.
But among those few serious events in the Roche study was the death of one patient. The 78-year old woman died of a brain bleed. It turns out that she had a rare bleeding disorder that is exacerbated by amyloid-busting drugs. The disorder was just added as a contraindication for the Lilly and Esai drugs. Roche will exclude such patients from its studies.
Roche's Phase 2 study focuses on dose levels and safety, so it isn't thoroughly testing for cognitive improvement in patients. Other drugs have shown that early and deep clearance of amyloid plaque leads to the best clinical outcome. So the rapid clearance achieved by trontinemab might be expected to deliver better clinical efficacy than the approved drugs, said Luka Kulic, who leads Roche's dementia studies.
Unlike most drug companies, Roche also has a diagnostics business. So its Alzheimer's studies are testing patients with some of Roche's experimental diagnostics.
Today, Alzheimer's patients are diagnosed and monitored with brain imaging techniques, like a PET scan, or with a spinal tap. Roche is developing simple blood tests that can find Alzheimer's, or rule it out, before symptoms appear.
"This field is really fast-moving," said Margherita Carboni, who leads development of the Alzheimer's tests. In the trontinemab study, the blood tests are confirming the drug's rapid action.
If trontinemab's numbers hold up in Phase 3 studies, doctors might be able to give patients a standard dose at widely spaced intervals, without constant monitoring.
"That is major change," said drug development chief Bonni. "It will have a major impact on the patients' burden."
Write to Bill Alpert at william.alpert@barrons.com
This content was created by Barron's, which is operated by Dow Jones & Co. Barron's is published independently from Dow Jones Newswires and The Wall Street Journal.
(END) Dow Jones Newswires
October 31, 2024 17:31 ET (21:31 GMT)
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