Lilly failure a blow for Alzheimer’s research, not end of road

By Ben Hirschler

LONDON (Reuters) – The failure of an experimental Alzheimer’s drug from Eli Lilly to slow cognitive decline, as many had hoped, has cast doubt on a main approach to fighting the disease, yet experts believe subtly different therapies could still work.

Lilly’s injectable antibody medicine solanezumab was designed to mop up a protein called beta amyloid that forms plaques in the brain and is believed to play a pivotal role in the disorder.

Other anti-amyloid drugs are also in clinical trials but they function in slightly different ways and, importantly, some are being tested at an earlier stage when there may be a better chance of improving brain function. Drug doses also vary.

“This is probably not the end for amyloid approaches,” said Elizabeth Coulthard, a dementia specialist at the University of Bristol, who nonetheless acknowledged the late-stage Lilly trial result was “very disappointing”.

John Hardy, professor of neuroscience at University College London, said the focus would now shift to another class of experimental drugs called BACE inhibitors, which are given as pills and work differently to block beta amyloid production.

Merck is currently leading in the BACE inhibitor race with its product verubecestat, which is being tested in two late-stage Phase III trials, the first of which is expected report results next year.

Lilly is also working on a rival BACE medicine with AstraZeneca.

Other companies with antibody treatments targeting beta amyloid in development include Biogen and Roche, which has a tie-up with biotech firm AC Immune.

Shares in these rival companies fell in the wake of the Lilly setback, as conviction in the beta amyloid treatment hypothesis faltered.

The failure is particularly disappointing given positive news last year suggesting that solanezumab might become the first drug ever to slow the progression of Alzheimer’s.

Currently approved drugs can do no more than ease some of the symptoms of the disorder and a successful disease-modifying treatment would be virtually guaranteed multi-billion dollar annual sales, industry analysts believe.

To date, however, the field has been littered with failures.

An analysis last year by the Pharmaceutical Research and Manufacturers of America found that between 1998 and 2014, 123 potential Alzheimer’s drugs were halted in clinical trials, while just four were approved.

Still, drug companies continue to lay bets in the hope of eventually tapping a huge market, with more than 70 experimental treatments in various stage of clinical testing.

“This is only one drug of several in the pipeline and they aim to tackle dementia in different ways, so we should not lose hope,” Jeremy Hughes, chief executive of Britain’s Alzheimer’s Society, said in response to the Lilly news.

Although the precise causes of Alzheimer’s are unclear, scientists believe the evidence implicating beta amyloid remains strong, although earlier-stage research is also focused on another protein called tau.

Experts will pore over detailed data when full results from the Lilly study are presented at a medical meeting next month, since while there was no statistically significant benefit over placebo, there was a directional trend favoring solanezumab.

(Editing by Giles Elgood)