Alzheimer’s Drug Aducanumab Promising Until Final Trials, Now Just Another Painful Failure

In a research field that has seen nothing but failures, one drug rose above the rest and gave us hope that there might soon be an effective treatment for Alzheimer’s disease. Recently, however, those hopes have been cruelly dashed as well.

The drug, called aducanumab, did present some side effects early on, such as headaches, but in its first two trial phases, the monthly intravenous infusions showed fantastic results, including clearer thinking for patients and a drastic reduction in the amount of amyloid-beta proteins present in the brain. These proteins are suspected to cause Alzheimer’s disease by blocking the normal flow of electrical signals between neurons.

Researchers were so excited about the positive results of aducanumab that they actually devised two separate trials to run at once for the drug’s third phase of testing. Titled “Engage” and “Emerge,” the trials were meant to investigate the effects of the drug on 2,700 patients from North America, Europe and Asia. Thousands of people around the globe were waiting to get into these trials when the research was brought to a dead halt.

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There were no safety concerns with the trial, but a futility analysis conducted by an independent data monitoring committee found that the drug trial was statistically unlikely to meet its core goals, making the money and effort put into a trial not worth it. Compared to a placebo, aducanumab simply wasn’t stacking up the way it needed to in order to help Alzheimer’s patients. A sad and anti-climactic end to a story that had built up so much hope for so many.

“This was the closest to the finish line and early results showed not only could we improve cognitive function but also get rid of amyloid in the brain,” said neurologist Dr. Richard Isaacson, who directs the Alzheimer’s Prevention Clinic at Weill Cornell in New York. “This was the most hopeful thing we had—in fact, I have patients who are in the study, patients that are waiting to get into the trials.”

Like many other drug trials before it, such as Eli Lilly’s solanezumab, Pfizer’s bapineuzumab, and Merck’s verubecestat, this drug trial may have failed in part because it focused on treating Alzheimer’s after the formation of plaques had already occurred and symptoms had begun to display themselves.

Pharmaceutical giant Biogen and its Japanese partner Eisai announced on Thursday, March 21, 2019, that they would be ending both phase three clinical trials of aducanumab early.

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“It was a huge gamble from the start,” said Harvard neurologist Dr. Rudy Tanzi, director of the Genetics and Aging Research Unit at Massachusetts General Hospital. “We know that amyloid deposition starts a decade or so before symptoms and it’s too late to treat it then. It’s like trying to put out a forest fire by putting out the match.”

But it’s difficult to run an Alzheimer’s trial on patients who haven’t been diagnosed with Alzheimer’s yet. Some drugs have been tested on people who were at risk of the disease, but each of those—like Johnson & Johnson’s BACE inhibitor atabecestat, which caused liver enzyme spikes in study participants—has also failed in its turn.

Researchers working on aducanumab had tried to dodge some of the issues other drug trials had had by enrolling patients who were in the very early stages of Alzheimer’s disease. They also believed that the drug was more potent than others in its class, allowing it to do a better job removing amyloid-beta plaques. But their ideas proved wrong, and Biogen is now in a sorry state, having put many of their eggs in this basket.

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For those closest to the failure, including patients, families, and researchers, the failure of aducanumab is a tough pill to swallow, even if it was a low chance of success from the beginning.

“This one hurts,” Dr. Isaacson said. “Alzheimer’s patients just can’t get a break.”

The trial hasn’t been a total loss, as details from the research will be presented at conferences to help inform future studies.

“I don’t think we should lose hope,” Dr. Isaacson said. “We understand that Alzheimer’s is a lifestyle disease and we need to intervene early to stop the progression. So I do think that there’s hope for this approach for prevention. But as for treatment for patients living with the disease now, this one hurts.”

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