Thursday, February 16, 2017

Another Potential Alzheimer's Disease Treatment Bites the Dust: What's Next?

And another one bites the dust.

Merck (NYSE: MRK) announced on Tuesday that it was halting a phase 2/3 clinical study of  in treating Alzheimer's disease. This news marked the second major clinical failure in recent months by a big drugmaker for a disease that still has no effective treatment. Eli Lilly (NYSE: LLY) reported disappointing results for solanezumab in treating Alzheimer's disease in November.

Why are these drugs proving to be ineffective? And is a pipeline candidate with a real shot at beating Alzheimer's disease anywhere in sight? 

Image source: Getty Images.

What's not working

Merck's  inhibits the beta-site amyloid precursor protein cleaving enzyme 1 (BACE1). BACE1 is an enzyme that's involved with the development of amyloid beta. Amyloid beta consists of pieces of protein that clump together and build up over time into amyloid plaque in the brain. The goal of BACE inhibitors is to prevent the buildup of this  and thereby slow the progression of Alzheimer's disease.

Verubecestat showed great promise in an early-stage study. Patients with Alzheimer's disease taking a 60 mg dose of the experimental drug experienced  reduction in the levels of beta-amyloid peptides.

Lilly's solanezumab also targeted the buildup of amyloid  but through a different mechanism. The humanized monoclonal antibody binds with soluble forms  the peptide that are thought to interfere with cognitive function.

But while  reduced amyloid beta, Merck's external data-monitoring committee stated that the experimental drug had "virtually no chance of finding a positive clinical effect" in improving cognition. Lilly's drug had already failed to improve cognition in two previous late-stage studies.

However, the drugmaker initially saw some potential for solanezumab in reducing cognitive decline in patients with a mild form of Alzheimer's disease. Lilly moved forward with another late-stage study, which also flopped.

More attempts

Although Lilly has thrown in the towel for solanezumab, Merck is continuing to evaluate  in a late-stage study for treating Alzheimer's patients with early symptoms of the disease. Lilly and AstraZeneca are partnering on their own BACE inhibitor, which is currently in a late-stage trial.

Roche (NASDAQOTH: RHHBY) has also run into dead ends in the past in treating Alzheimer's disease. Gantenerumab disappointed in a previous phase 3 study targeting the indication. However, Roche thought the experimental drug might have a better chance of success given in higher doses. The company has two late-stage studies currently in progress, one for gantenerumab plus another for crenezumab.

Biogen (NASDAQ: BIIB) claims one of the most promising Alzheimer's disease candidates right now. The biotech announced encouraging results from an  study of aducanumab in 2016. These results showed  in amyloid plaque, and more importantly, the rate of clinical decline in patients. Aducanumab is now in a late-stage study.

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Other theories

Note that all of the drugs mentioned thus far target reduction of amyloid beta. There are other thoughts, however, about how to treat Alzheimer's disease. A major alternative theory involves preventing  of tau proteins. Like amyloid beta, tau protein deposits have been found in the brain cells of Alzheimer's disease patients.

A couple of companies are pursuing the  theory. Slovakian biotech AXON Neuroscience has a phase 2 study of its AADvac1 tau vaccine in progress. AC Immune is working with Johnson & Johnson on tau vaccine ACI-35 and with Roche on an anti-tau antibody. Both experimental therapies are in early-stage testing.

Story Source: The above story is based on materials provided by BILLINGSGAZETTE

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