Back in 2015, biotech juggernaut Biogen (NASDAQ:BIIB) made headlines on the news that its investigational Alzheimer's disease (AD) treatment aducanumab showed strong efficacy in an early-stage clinical trial. This devastating disease affects millions of Americans, and the scope of the issue has analysts estimating that a successful AD treatment could be worth as much as $20 billion by 2030. Unfortunately, however, the battleground of biotech is littered with the remains of previous "game-changing" therapies -- all of which ended in failure. Despite Biogen's best intentions, I, for one, believe aducanumab will be no exception.

The story thus far

All the way back in March 2015, Biogen announced positive top-line results from a phase 1 clinical trial of aducanumab in AD patients. The trial tested two dosages, 3-mg and 10-mg, both of which led to improvements in cognitive function. Intriguingly, the 10-mg dose showed greater efficacy in improving cognitive function as compared to the 3-mg dose. Higher doses triggering a stronger response is usually seen as a good sign of the drug's effectiveness. Unfortunately, though, the 10-mg dose was also associated with an increased rate of dangerous brain swelling unseen in the 3-mg arm.

Armed with this data in hand, Biogen then quickly proceeded to launch a new 6-mg "goldilocks" dosing study with the hopes that this 6-mg dose would show greater efficacy than the 3-mg dose, but without the dangerous brain swelling associated with the 10-mg dose. These hopes were dashed in July of 2015 when Biogen announced that the 6-mg dose both was ineffective and had a worse safety profile than the 10-mg dose.

So why all the hype? Following the failure of aducanumab in 6-mg, Biogen continued 165 patients in early stages of the disease from the phase 1 studies into a long-term phase 1b study. Late last year, Biogen released data from this long-term study indicating that aducanumab slowed cognitive decline for these early-stage patients.

Currently, Biogen is progressing aducanumab in a pair of long-term phase 3 trials for early stage patients with AD. These trials are expected to read out in 2020.

hand pulling block from Jenga tower

Image source: Getty Images.

So what's the problem?

The fundamental problem with aducanumab is that the drug relies on the "amyloid hypothesis" of treating Alzheimer's disease. Allow me to explain. While scientists are still uncertain as to the underlying cause of AD, scientists have observed large quantities of a protein fragment known as "amyloid-beta" accumulated in the brains of AD patients. The proteins tend to stick to each other until enough gather to form what is known as an "amyloid-beta plaque." When enough of these plaques develop in the brain, they have the effect of blocking cell-to-cell communication, leading many researchers to think that they are the underlying cause of AD.

Aducanumab's purpose is to destroy these plaque buildups in the patient brain. Aducanumab is a monoclonal antibody (a lab-produced immune cell that has been programmed to specifically attack one target) that works to destroy beta-amyloid deposits. In aducanumab's long-term phase 1b study, the drug was shown to be highly effective in clearing out the amyloid plaques.

Unfortunately, however, aducanumab is only the latest in a long line of potential AD products which have shown this effect. Back in 2012, Pfizer and Johnson & Johnson's bapineuzumab showed a similar ability to clear amyloid plaques from the brain. However, in late-stage trials, while bapineuzumab did continue to clear this plaques, the drug did not demonstrate the ability to slow or halt the underlying progression of AD. Similarly, Eli Lilly's solanezumab, which also showed promising ability to destroy amyloid, failed in 2016 to demonstrate disease-slowing effects for AD in late-stage clinical trials.

Unknown unknowns

While scientists may still be investigating the underlying cause of AD, it seems clear that the destruction of amyloid plaques has little ability to slow the progression of the disease. Although the market is eagerly anticipating Biogen's pair of aducanumab studies reading out in 2020, I wouldn't hold my breath. My advice to Biogen? Stick to what you know -- multiple sclerosis. My advice to the researchers working on a cure for Alzheimer's? It's time for a novel approach.

David Liang has no position in any stocks mentioned. The Motley Fool owns shares of and recommends Biogen and Johnson & Johnson. The Motley Fool has a disclosure policy.