Researchers have believed that Alzheimer's disease is caused by the buildup of a sticky protein called beta-amyloid. According to this amyloid hypothesis, the protein forms plaque in the brain that damages and eventually destroys brain cells.
This hypothesis is now in question. To date, test results of amyloid therapies to treat Alzheimer’s have been disappointing, to say the least. But several researchers think the death of the amyloid hypothesis is premature. That provides at least a sliver of sunshine for the companies that still have amyloid compounds in clinical trials, including Biogen (BIIB, Financial), Amgen (AMGN, Financial) and Novartis (NVS, Financial).
Eli Lilly (LLY, Financial) is no longer among the group. The company was the first to throw in the towel when it abandoned its anti-amyloid compound, solanezumab, after negative clinical trial results. At the end of last year, Biogen and its partner, Eisai, piled on with some more bad news. The companies reported their protofibril antibody would fail to meet endpoints in a mid-stage clinical trial.
Biogen’s stock slid about 4% on that piece of disappointing news and has since dropped another 10% to $285. Despite the major setback, the companies said the blinded study will continue and that a comprehensive data analysis will be demonstrated at 18 months in hopes of demonstrating clinically significant results. The results of the final analysis are expected to be obtained during the second half of 2018.
In an editorial published earlier this year in the New England Journal of Medicine, Alzheimer’s researcher M. Paul Murphy of the University of Kentucky said it may be time to abandon the anti-amyloid approaches and look for other approaches to stop the progression of Alzheimer’s.
Not so fast, say others in the field. They think getting rid of amyloid can be the right treatment -- if given to the right patients at the right time.
One of those amyloid boosters is Brigham and Women's Hospital neurologist Reisa Sperling, who co-directs the Harvard Aging Brain Study at Massachusetts General Hospital. She told the newsletter CommonHealth that while the large clinical trials have officially failed, they all showed a hint of effectiveness.
That’s one of the reasons she’s running a trial giving solanezumab to more than 1,100 people who have some amyloid in their brains, but who don’t have any of the devastating symptoms of Alzheimer’s, such as losing the ability to care for themselves along with decades of memories.
Sperling thinks the studies have failed because you need to go after amyloid plaque 10 years before it starts to build up. So in one of her studies, she’s going to be giving solanezumab to volunteers who have some amyloid in their brains but haven’t yet developed symptoms of Alzheimer’s.
A number of companies with a lot riding on amyloid plaque therapy are crossing their fingers that Sperling is on to something. With favorable results and ultimately approval, Biogen’s aducanumab could generate sales of $1.5 billion by 2022. In addition, Biogen is developing an anti-amyloid anantibody that is currently in phase two trials. Its third Alzheimer’s drug, elenbecestat, is being co-developed with Eisai.
Amgen and Novartis have a BACE (beta-secretase cleaving enzyme) inhibitor in phase two testing, and the compound has been fast-tracked by the Food and Drug Administration. AbbVie’s (ABBV, Financial) anti-tau antibody is in phase two studies for Alzheimer’s and progressive supranuclear palsy. It has both fast-track and orphan-drug status in the latter indication.
The smaller vTv Therapeutics (VTVT, Financial) is in phase three for azeliragon, a type of drug that is to play a role in inflammation, amyloid buildup and tau phosphorylation.
Disclosure: The author has positions in both AMGN and LLY.
