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Regular-article-logo Thursday, 25 April 2024

Drug fails in Alzheimer’s study

Roche setback blow to people whose genes make them vulnerable

Reuters Zurich Published 10.02.20, 08:31 PM
Researchers still hope to tame a condition that affects40 million people worldwide

Researchers still hope to tame a condition that affects40 million people worldwide (Shutterstock)

Experimental drugs from Roche and Eli Lilly failed to halt Alzheimer’s disease in their latest test, the companies said on Monday, in a blow to people whose genes make them particularly vulnerable to the illness.

Pursuit of an Alzheimer’s remedy, which would inevitably reap drugmakers billions of dollars, has been marked by more than 100 failures, although researchers still hope to tame a condition that affects nearly 6 million Americans, more than 40 million people worldwide, and which is growing more prevalent.

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The study of Roche’s gantenerumab and Eli Lilly’s solanezumab spearheaded by Washington University in St Louis focused on rare autosomal dominant Alzheimer’s disease, which is caused by gene mutations that follow generations of families.

Those afflicted often develop Alzheimer’s disease before the age of 60 and have a 50 per cent chance of passing the mutation on.

By targeting this group, scientists had hoped the medicines would arrest their cognitive decline. Years after the trial began, however, they concluded the drugs were not working.

“We are very grateful to all those involved in this study and hope the data can further contribute to the science and collective understanding of this complex disease,” Roche’s Chief Medical Officer Levi Garraway, said in a statement.

Like many other Alzheimer’s drug prospects, gantenerumab and solanezumab are designed to neutralise beta-amyloid plaques seen as a driver behind brain cell death.

Garraway said a pair of separate Roche studies of gantenerumab against a form of Alzheimer’s disease not directly caused by gene mutations would continue. It is due to produce results in 2022.

Roche is also testing gantenerumab in humans as part of its work with a “brain shuttle” technology it hopes boosts penetration into the brain, where the drug is needed.

“At this time, Lilly does not plan to pursue a submission for solanezumab in people with dominantly inherited Alzheimer’s disease,” the company said in a statement.

Lilly said the study’s outcome will not impede its separate solanezumab study in asymptomatic Alzheimer’s disease.

These failures mark just the latest disappointments with gantenerumab and solanezumab.

For Roche, dosing of people thought to be in the early, or prodromal, stages of the disease was halted in 2014.

For Eli Lilly, solanezumab has missed the mark in several studies, including a trial against mild Alzheimer’s disease that the Indiana-based company announced had failed in 2016.

Washington University professor Ronald Bateman, who led the latest trial, said its emerging insights include that brain changes as Alzheimer’s progresses are much the same in people with inherited, early-onset and late-onset disease.

“Ongoing and continued research and trials will bring us closer to our goal to stop Alzheimer’s,” Bateman said on the university's website.

“We will continue until we are successful.”

Both the early-onset and late-onset forms of Alzheimer’s have “silent” phases that begin up to two decades before symptoms arise.

The process starts with the accumulation of plaques of the protein amyloid beta in the brain. Eventually, as the disease progresses and the damage to the brain becomes more extensive, people’s memory, thinking and behaviour start to deteriorate.

Both investigational drugs are designed to target and neutralise amyloid beta in the brain through different mechanisms and are being evaluated in other, more common forms of Alzheimer’s.

“We are grateful to the courageous participants, their families, and clinical investigators for their dedication and commitment to the study,” said Daniel Skovronsky, MD, PhD, Lilly’s chief scientific officer and president of Lilly Research Labs.

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