After Merck & Co. & Eli Lilly Alzheimer’s Failures, A Look at 7 Companies Still on the Hunt

Published: Feb 20, 2017

After Merck & Lilly Alzheimer’s Failures, A Look at 7 Companies Still on the Hunt February 17, 2017
By Mark Terry, BioSpace.com Breaking News Staff

Alzheimer’s disease is clearly a tough nut to crack. Most recently, on February 15, Merck & Co. halted its Phase II/III trial of verubecestat in patients with mild-to-moderate Alzheimer’s disease. Last year, Eli Lilly and Co. had a dramatic failure of solanezumab. The list can go on and on.

Benzinga looks at what companies have the most promising Alzheimer’s drugs and why concern is growing that our understanding of the disease is underlying the failures.

1. Eli Lilly

Despite the failure of solanezumab, the company is still studying a beta secretase enzyme (BACE) inhibitor, AZD3293, in Phase II/III studies, with patient enrollment in another. Benzinga notes, “Concerning, however, is that the BACE inhibitor approach is what just failed for Merck. When asked how Merck’s trial suspension may read-through for Lilly , the company told Benzinga, ‘Lilly can’t comment on how or if these results will impact our program, but we look forward to Merck making these data available as soon as they can.”

2. Biogen

Biogen , generally believed to have the most promising drug in the pipeline for Alzheimer’s—which may not be something to brag about—aducanumab targets amyloid plaque build-up with an antibody instead of BACE inhibitor. Early trials have been promising, but final data isn’t expected until 2019.

December 2016 results in a Phase Ib trial were promising. More than 100 patients receiving the drug showed a drop in Alzheimer’s-related beta-amyloid plaque in the brain, as well as continued to show a slowing of cognitive declines. It’s worth noting that aducanumab is very similar to Lilly’s solanezumab.

3. AC Immune and Genentech

AC Immune , along with Genentech is working on crenezumab for patients with mild AD. Like aducanumab and solanezumab (the “ab” at the end is the clue), crenezumab is an antibody, also targeting amyloid proteins. Patients are being enrolled in a Phase III trial.

Symptoms Versus Causes

There are four AD drugs approved by the U.S. Food and Drug Administration (FDA), and they all treat symptoms, not the disease. Several companies are also working on drugs in this area.

4. Allergan

Allergan has several drugs for AD symptoms, Namenda and Namzaric. Allergan made licensing deals with Heptares Therapeutics and acquired Chase Pharmaceuticals, both of which had drugs in development to treat AD symptoms.

5. Axovant

Axovant 's interpirdine showed promise in a Phase IIb trial. Bazinga writes, “Intepirdine is currently in trials with mild-to-moderate AD patients with data expected this year, but its odds of success have come into question after a similar drug being developed by Danish pharmaceutical company Lundbeck failed its pivotal Phase III study.”

Different Approaches

6. Neurotrope

Neurotrope has bryostatin, which will soon announce Phase II data. The drug is being developed to reverse, as opposed to treat, the disease in late-stage patients. It is designed to regenerate degraded synapses. Data is expected in April.

7. Accera

Accera is a private company backed by Nestle. It plans to announce Phase III data for AC-1204 in March. Bazinga writes, “Accera’s drug approaches AD as a metabolic condition that can be combated by stimulating a mild form of ketosis by generating ketones for use in neurons, improving neuronal metabolism and cognition and function in patients with mild to moderate AD.”

Questioning the Mechanisms

As drug after drug fails, at least some researchers—and clearly some investors—are beginning to question our understanding of AD. The predominant theory is that the creation of amyloid plaques causes the brain damage that leads to loss of cognition and memory. But the drugs that seem to successfully clear amyloid in early trials, don’t seem to make much improvement in cognition and memory. It’s possible that the damage has already been done and the drugs don’t really improve that, or it’s possible that there’s a fundamental lack of understanding about the disease and the role of amyloid plaques.

Daniel Alkon, chief scientific officer of Neurotrope, told Benzinga after Merck’s failure, “Here’s the punchline. It’s the same target—getting rid of amyloid. That target has been shown over and over again for 20 years not to be correlated with the causing of deficits. The only that that’s well correlated, clearly established, is the loss of the synaptic connections.”

And Alkon is not the only scientist to criticize the amyloid hypothesis. Clive Holmes, professor of Clinical Neurosciences, University of Southampton, Southampton, UK, published a paper in the Lancet nine years ago that criticized the theory, and Michael Gold senior medical advisor for Accera, has as well—although it can be pointed out that Alkon and Gold are hardly unbiased in their belief in alternate mechanisms of action.

Another thing that has been pointed out is that clinical trials in AD have been increasingly moving the patient population earlier and earlier in the disease. Alkon told Bazinga, “These trials are not working, and moving it up earlier and earlier is not going to change it. Look at Biogen’s trial. What people don’t realize is that Biogen moved their trial so far up that there wasn’t one Alzheimer’s patient in the trial. They only looked at people who were mild cognitively impaired or confused. Only half of which go on to get Alzheimer’s.”

Although all the failures of Alzheimer’s drug is disheartening, with any luck, these are examples of Thomas Edison's crede: “I have not failed. I’ve just found 10,000 ways that won’t work.”

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