Doubts over BACE drugs after Merck ends Alzheimer's trial

Closeup of X-ray photography of human brain

Merck & Co has ended a second phase 3 trial of its Alzheimer’s drug, verubecestat, after an interim analysis found that it was unlikely to succeed in slowing the progression of the disease in its early stages.

This is the latest in a series of disappointments in Alzheimer’s, with Boehringer Ingelheim deciding to axe its BI 409306 late last week after another trial failure.

The disease is proving very difficult for pharma to tackle, and Merck’s decision casts doubt on the class of drugs known as beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitors.

Inhibiting BACE1 is thought to prevent formation and build-up of the protein known as amyloid that are often found in the brains of people with Alzheimer’s.

AstraZeneca and Eli Lilly are also co-developing a BACE drug, AZD3292, or lanabecestat, which is in phase 3 development and received Fast-Track designation from the FDA in 2016.

The companies will have an anxious wait for the results of a phase 3 study due in September next year after this second failure from Merck’s drug.

Merck said yesterday that it had decided to stop the placebo-controlled phase 3 APECS study in early stage disease after the trial’s independent data monitoring committee said the benefits of the drug were unlikely to outweigh its risks following an interim analysis.

A year ago, the independent committee on the separate phase 2/3 EPOCH trial in patients with mild to moderate disease concluded there was “virtually no chance” verubecestat would help patients with the mild to moderate disease.

There was no immediate word from Merck about whether it will continue development – but with no other active trials of verubecestat it looks like this is game over for yet another Alzheimer’s drug.

Further details will be presented at an upcoming medical meeting, Merck said.

[caption id="attachment_24785" align="alignnone" width="166"] Merck's Roger Perlmutter[/caption]

Roger Perlmutter, president of Merck Research Laboratories, said: “We are disappointed with this outcome, especially given the lack of treatment options for patients suffering from Alzheimer’s disease.”

“We are grateful to the patients and caregivers who participated in this study, and despite this outcome, Merck remains committed to developing novel therapies for the treatment of Alzheimer’s and other neurodegenerative diseases.”

The reaction from twitter indicates that there are now serious doubts about whether BACE drugs will work, as well as the hypothesis that amyloid causes Alzheimer's.

Hopes are now resting with drugs such as Biogen’s aducanumab, which works against amyloid and could report preliminary phase 3 results next year.

Roche is also soldiering on with crenezumab in phase 3, another drug targeting amyloid.

Pharma has not given up the hunt for new drugs for Alzheimer’s – despite the setbacks a report by ResearchersAgainstAlzheimer’s last year found there are dozens of drugs in the pharma pipeline that could become new treatments if trials are successful.