November 22, 2016
By Mark Terry, BioSpace.com Breaking News Staff
Drug development for Alzheimer’s disease (AD) has been a wasteland of failed trials, with hundreds of drugs abandoned after failures. In fact, between 2002 and 2012, only one of 244 AD drug candidates was approved, a 0.4 percent success rate. At least part of the trouble seems related to an incomplete understanding of what causes Alzheimer’s.
Although there is clearly a role played by beta-amyloid plaques, there also appears to be damage caused by tau proteins, which typically appear later in the disease process.
With a market that could exceed $13 billion by 2023, companies are still gambling on Alzheimer’s drugs. Keith Speights, writing for The Motley Fool, takes a look at five companies that could potentially dominate the AD market if their pipeline drugs get approved.
One focus is on BACE, or beta secretase cleaving enzyme inhibitors. BACE is linked to the development of amyloid beta. This area focuses on drugs that stop the buildup of amyloid plaques.
The companies working in this area include AstraZeneca , Eli Lilly and Merck . AstraZeneca and Lilly are collaborating on AZD3293, currently in two Phase III trials.
Merck also has verubecestat in late-stage studies, and is planning data for late 2017. Speights writes, “The company recently announced positive findings from an early-stage study of the drug, with patients at the highest dosage of verubecestat experiencing an 84 percent reduction in amyloid beta.”
Both AstraZeneca and Lilly received Fast Track designation from the U.S. Food and Drug Administration (FDA).
A second focus is on monoclonal antibodies. These antibodies would attack amyloid plaque. The difference from BACE, then, is that BACE attempts to prevent the buildup of amyloid. Antibodies would attack amyloid as, or after, it develops.
Lilly’s solanezumab is in a late-stage study with this approach. Speights writes, “Mid-stage studies of the drug didn’t show significant improvement versus placebo. However, Lilly moved forward with solanezumab anyway, changing the late-stage study in March to only have one primary endpoint: improvement in cognition.”
Biogen ’s aducanumab is also a monoclonal antibody. In September, the FDA granted it Fast Track status. Speights writes, “Early studies showed significant potential for the drug. There’s still a long way to go, though. The primary outcome results for the late-stage studies of aducanumab won’t be available until 2020.”
Roche is also a player, with two monoclonal antibodies, gantenerumab and crenezumab, in late-stage clinical trials. But neither drug met primary endpoints in a mid-stage trial.
Any of these companies could be successes or failures. Speights thinks that Biogen and AstraZeneca/Lilly partnership have the best chance, but it’s too early to really know.
And it’s worth noting that they’re not the only companies, large or small, working in the area. Pfizer (PFE), for example, seems to be quietly building its AD pipeline. The company’s PF-06648671 focuses on beta-amyloid, as does PF-06648671, which is being evaluated in combination with midazolam, an anesthetic.
The Pharmaceutical Research and Manufacturers of America indicates that there are 77 experimental compounds this year being developed for AD. Many are in Phase I, but not all. Companies include AZTherapies, Archer Pharmaceuticals, Avanir Pharmaceuticals , vTv Therapeutics , Lundbeck (LUN) with Otsuka Pharmaceutical, GlaxoSmithKline , Amgen , Transition Therapeutics , Grlfols USA (GRFS), Impel NeuroPharma, Takeda Pharmaceuticals , Axovant Sciences , TauRX Pharmaceuticals and Johnson & Johnson .
“The heart of the matter,” George Budwell wrote for The Motley Fool, in October, “is that an effective disease modifying treatment may require something along the lines of an anti-amyloid agent, another compound that slows the reformation of plaques, and still another to treat downstream events such as neurofibrillary tangles. And that’s where Pfizer ’s efforts in AD could be headed, making it a key clinical program to keep an eye on moving forward.”
