Hopes for new Alzheimer’s treatment dashed as drug misses clinical trial targets

An immunotherapy drug hailed as a potential game changer in the treatment of Alzheimer’s has missed its targets in a large-scale clinical trial.

The antibody treatment, solanezumab, failed to achieve significant slowing of memory loss and mental decline caused by the disease.

As a result, manufacturer Eli Lilly and Company will not be seeking regulatory approval for the drug to be used to treat mild Alzheimer’s.

Leaders of Britain’s two main Alzheimer’s charities described the outcome as “disappointing” while other experts said they were not surprised by the set-back.

Currently while some of the symptoms of the disease can be treated, there is nothing in the medicine chest that can halt or slow its progression.

Solanezumab is one of several new drugs being tested that target toxic deposits of protein fragments called beta-amyloid which build up in the brains of Alzheimer’s sufferers.

Pre-clinical research indicated that by mimicking an immune system attack on beta-amyloid, the drug might have a chance of reversing the disease.

Doubts were raised when two earlier trials recruiting patients with mild to moderate Alzheimer’s failed to meet their primary “endpoints” – targets by which the effectiveness of a new medicine is judged.

The latest Phase III trial, Expedition 3, was restricted to patients shown by brain scans and spinal fluid tests to have high levels of beta-amyloid.

The international trial involved 2,100 people with mild Alzheimer’s disease who were tracked for 18 months. Some were given solanezumab while others were treated with an inactive “dummy” placebo drug.

Dr David Reynolds, chief scientific officer at the charity Alzheimer’s Research UK, said: “It’s very disappointing that solanezumab has not shown benefit for people with mild Alzheimer’s and will no doubt trigger important debate within the research community.

“We only have headline information today, so we’ll need to see the full data to understand why solanezumab didn’t show benefits and what researchers must learn from the findings.

“Solanezumab is designed to mop up amyloid protein – a key hallmark of Alzheimer’s – and is the result of years of development based on the concept that this protein is a central driver of the disease.

“While today’s results are a setback for the amyloid hypothesis, there are several other anti-amyloid drugs still in clinical trials that work in different ways, some of which are being tested even earlier in the disease process than solanezumab.

“We can’t disregard these ongoing trials and their findings will now be more important than ever in shaping the search for disease-modifying treatments for Alzheimer’s.”

Jeremy Hughes, chief executive at Alzheimer’s Society, said: “After positive news last summer we had high hopes for this drug to become the first to slow down Alzheimer’s disease. It’s extremely disappointing to learn that it hasn’t delivered a meaningful change for people living with dementia, when the need is clearly so great.”

But two British experts, Professor Peter Roberts, from the University of Bristol, and Professor Robert Howard, from University College London, said the results were not unexpected.

Prof Roberts said: “I am not in the least surprised by the solanezemab data, despite Lilly’s seeming optimism just a short while ago.

“There is still no convincing evidence that shows a clear relationship between amyloid deposition and deficits in cognition in humans.”

Robert Howard, a professor of old age psychiatry, said: “This is disappointing but not a great surprise.

“Like other agents in this class, the drug engages with the target in terms of demonstrably reducing brain amyloid but this doesn’t appear to reverse or slow cognitive and functional decline.”

Eli Lilly has not entirely given up on solanezumab and is said to be considering another Phase III trial aimed at patients suffering from an early-stage condition known as “prodromal Alzheimer’s”.

These patients experience memory and thinking problems not severe enough to justify a diagnosis of dementia but have signs of beta-amyloid build-up.

Dr John Lechleiter, the company’s chairman and chief executive, said: “The results of the solanezumab Expedition 3 trial were not what we had hoped for and we are disappointed for the millions of people waiting for a potential disease-modifying treatment for Alzheimer’s disease.

“We will evaluate the impact of these results on the development plans for solanezumab and our other Alzheimer’s pipeline assets.”

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