Merck pulls promising late-stage drug trial

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The most promising clinical trial for an Alzheimer’s drug has been pulled as a review showed it is unlikely to work.  

Merck & Co Inc was widely tipped to be a frontrunner in the global race to find a treatment for the incurable neurodegenerative disease – and in doing so, earn billions.

But the once-exciting trial has slowly spluttered to a halt: the firm shelved a similar trial of the same drug Verubecestat in late-stage patients last year, but had hoped it could work in early or mid-stage sufferers.

On Tuesday, executives were forced to admit defeat, dealing an ominous forewarning to the four other major pharmaceutical companies which have bet big on this inhibitor, BACE1, to treat the disease.

However, hours after Merck announced the end of the trial, a team at Cleveland Clinic published a surprising study which found BACE1 inhibitors not only treated Alzheimer’s but completely eliminated it in mice with early stages of the disease.   

Verubecestat belongs to a class of experimental Alzheimer’s drugs called BACE1 inhibitors that target an enzyme involved in the formation of the toxic amyloid protein that turns into plaques in the brains of Alzheimer’s patients.

In Merck’s trial, patients were given either a placebo, or 12mg or 40mg of verubecestat, once a day. 

There have been a number of high-profile failures in Alzheimer’s drug development in recent years. 

Pfizer Inc said last month that it was abandoning research to find new drugs aimed at treating Alzheimer’s and Parkinson’s disease.

Lilly previously endured multiple failures with its solanezumab, which also targets beta amyloid, but in a different way. 

In the most recent setback, Lilly said that drug failed to slow declines in mental capacity of patients with even mild symptoms. 

Roche did away with BACE1 inhibitors in 2013. 

Others are still clinging on. 

Biogen and Eisai are also in advanced clinical trials testing a similar but subtly different BACE inhibitor – E2609 – in early-stage patients.

Meanwhile, Amgen and Novartis are testing a BACE inhibitor known as CNP520, which they are testing on people at-risk of Alzheimer’s, to see if it could work preventatively. 

There was one ringing endorsement this morning for BACE1 as a prospect to tackle Alzheimer’s: a team at Cleveland Clinic published a paper showing they had successfully reversed Alzheimer’s in a middle-aged lab mouse.

Their trial used a BACE1 inhibitor, essentially the same method as Merck’s, in a similar aged subject. 

They claim their tests on a 20-month-old mouse – equivalent to a 50-year-old human – show it could be possible to halt the disease if it is caught decades earlier than usual. 

Lead author Riqiang Yan admitted he was ‘shocked’ when their attempts to reduce amyloid plaque in mice completely eradicated the dangerous build-ups that slowly cripple the brain.

Already aware of the Merck failure, Yan told Daily Mail Online last night that he still believes BACE1 is the answer to preventing and treating Alzheimer’s. 

Yan envisions a future when these enzymes, known as BACE1 inhibitors, could be available as a vitamin that all humans take preventatively to stave off neurodegenerative disease.

‘We were surprised it worked so well, we saw complete reversal,’ Yan, who will start as chair of the department of neuroscience at the University of Connecticut this spring, said.

‘To our knowledge, this is the first observation of such a dramatic reversal of amyloid deposition in any study of Alzheimer’s disease mouse models.’   

 

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