A breakthrough approach to treating Alzheimer's is facing major setbacks

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  • Many promising Alzheimer's drug trials have failed in the past few months.
  • The latest trial from drugmaker Merck stopped Tuesday after a committee found that the drug had "virtually no chance of finding a positive clinical effect."
  • These drugs are based on the "amyloid hypothesis," which some are still hopeful will be a successful way to treat Alzheimer's even with these setbacks.

It's been a hard few months for promising Alzheimer's clinical trials.

The disease in its mildest form is characterized by symptoms including memory lapses, getting lost, repeating questions, and misplacing things - behaviors that generally get more severe over time.

By 2050, the number of people living with Alzheimer's in the US alone is projected to triple to an estimated 13.8 million.

Right now, there are only four treatments that treat the symptoms of Alzheimer's, and the hits just keep coming for potential new treatments in development. (On average about 99% of all drugs in clinical trials never actually make it to approval.)

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On Tuesday, drugmaker Merck stopped its late-stage trial of its drug, verubecestat, in patients with mild to moderate Alzheimer's, after a committee found that there was "virtually no chance of finding a positive clinical effect."

The hope was to have the drug stop the disease from progressing. Merck said it's still working on another late-stage trial for the drug to treat people with even earlier stages of the disease, and those results are expected in 2019.

The results came less than a week after another Alzheimer's drug that was hoping to treat the symptoms of the disease failed two key clinical trials.

The amyloid hypothesis is taking a beating

So far, 2017 isn't looking much different from 2016, when there were four major flops for Alzheimer's drugs, including a highly-anticipated treatment from pharmaceutical giant Lilly.

That drug, solanezumab, as well as Merck's verubecestat came out of research on the "amyloid hypothesis," or the idea that targeting beta amyloid deposits in the brain to clear them out was the way to go about treating the disease. In people who have Alzheimer these deposits build up in certain parts of the brain, but it's still not known whether the plaques cause the disease, or are just a byproduct.

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But solanezumab failed to slow down cognitive decline in patients with Alzheimer's; those in tests who took a placebo fared about the same.

"It's not what we wanted, it's not that leap forward for patients, but it's a step forward for the science," Dan Skovronsky, Lilly's senior vice president of clinical and product development, told Business Insider in January.

Skovronsky said that progress was related to being able to screen patients for the very thing they were trying to target, something that he said seems intuitive but isn't. "What it's telling us is that there's a small effect on disease progression. But it's not zero. It's a clue that we're headed in the right direction."

Skovoronsky said that despite some setbacks, he remained more encouraged than ever by the amyloid hypothesis. Even so, Lilly has stopped its remaining phase 3 solanezumab trial, turning the focus onto the company's BACE inhibitor - the same kind of approach that the Merck drug took.

Lilly's not the only one that's holding on hope for the amyloid hypothesis. Bernstein analyst Ronny Gal noted that Merck's trial was expected to fail, in particular because it didn't screen for people with beta-amyloid plaques before getting started (diagnostics that screen for the plaques are still relatively new). That's not the case with the other trial Merck's continuing, where they're targeting people with even earlier stages of Alzheimer's. And treating as early as possible could be the key to proving out the amyloid hypothesis, Roger Pelmutter, Merck's head of research and development told Forbes.

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"Because Alzheimer's progresses over a period of decades, it's understandable that it might be necessary to get in really quite early," he said.

There will be more opportunities to see that hypothesis in action, too. Biogen, another company that's big in neuroscience, expects to have data on its beta-amyloid targeting treatment in 2019.

There's still more ahead in 2017, and not all rely on the amyloid hypothesis

While a lot seems to hinge on the amyloid hypothesis, drugmakers are working on other approaches that could be game-changing. Accera, the company looking into the metabolic aspects of Alzheimer's, will have data coming out on its phase three trial in the first quarter of 2017.

And Axovant, whose drug aims to treat the symptoms of Alzheimer's, will have phase three data coming out in the second half of 2017. Some of Axovant's competitors that have been going after the same target have had less-than stellar results.

On February 8, drugmaker Lundbeck announced its 5-HT6 antagonist had failed two key trials, quashing any last hopes for that particular drug.

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