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Despite drug setback, researchers encourage hope for Alzheimer’s treatment

🕐 4 min read

Alzheimer’s is one of the leading causes of death in the U.S. and the only disease among the top 5 for which there is no treatment. Prospects got even bleaker this week when an Eli Lilly & Co. experimental drug failed.

Still, researchers and investors alike are urging the industry not to give up. And pharmaceutical companies, even those that had pulled out of the search for a treatment in the past, are responding with a renewed commitment – for now.

“This is such a devastating disease, and it’s so important for scientists to continue to push through this,” said Rita Balice-Gordon, the recently arrived head of neuroscience at Sanofi. “I’m committed to beating the drum for doing well-reasoned and well-researched clinical experiments, which will help drive the field collectively forward.”

Alzheimer’s research has already consumed more than $3 billion in spending over 27 years at Lilly alone, and the failure of its solanezumab treatment sent shares tumbling Wednesday. Lilly’s drug, which is targeting the amyloid protein that builds up in patients’ brains, didn’t slow their inexorable mental decline, adding to growing evidence that finding a way to treat the leading cause of dementia in the world may be even more herculean than experts expected.

Sanofi’s Balice-Gordon is under no illusion about the effort to find a treatment, predicting additional failures are coming for a disease that is already littered with setbacks. The Paris-based company is moving gradually, and perhaps seeking a partner, for a compound in early-stage development. Yet her commitment is particularly apt because Sanofi pulled back from Alzheimer’s research a few years ago under former Chief Executive Officer Chris Viehbacher.

Lilly, too, plans to stick with its Alzheimer’s research. The Indianapolis-based company has one of the broadest pipelines in the industry, with a half a dozen Alzheimer’s drugs in development, said incoming CEO David Ricks.

Biogen Inc., Merck & Co. and Roche Holding AG, which all have late-stage – known as phase 3 – trials, offered similar perspectives, saying they remained confident in their clinical programs and stressing that each therapy is designed to attack the condition in different ways.

“We don’t think that it – by itself, one therapeutic – negates the amyloid hypothesis,” said Samantha Budd Haeberlein, head of Alzheimer’s clinical development at Biogen, which has generated promising early results with its drug, aducanumab. “Disappointing, for sure, but for us it doesn’t shake our confidence going forward.”

The jury is still out for the amyloid theory, which argues that the accumulation of the sticky protein in the brains of patients with Alzheimer’s is actually the root cause of the disease.

“It’s absolutely unclear,” said Tony Butler, an analyst at Guggenheim Securities who recommends buying Lilly shares. Vamil Divan, an analyst at Credit Suisse, also urged caution. Lilly’s solanezumab could possibly be used as a combination therapy, or at a different dosage, he said.

“I wouldn’t throw the amyloid hypothesis out on this data,” said the analyst, who rates the shares outperform. “We’re still making incremental progress.”

Studies have shown that removing the amyloid plaques that congregate between the synapses in the brain, the ones used to definitively diagnose Alzheimer’s during an autopsy, isn’t enough to reverse the disease’s mental impairment. Lilly’s latest trial was done in patients with a mild form of the disease. While there was a suggestion that patients getting solanezumab may have done better than those given a placebo, the difference wasn’t meaningful, and Lilly threw in the towel for that patient group.

One hope may be treating patients at an earlier age, before there are any signs or symptoms of disease. Research shows that amyloid plaque begins building decades before there is evidence of mental impairment, and stopping it then may be the best shot at benefit, said Rudy Tanzi, a professor of neurology at Harvard Medical School and director of the genetics and aging research unit at Massachusetts General Hospital.

“It is simply too late to treat amyloid in mild patients,” Tanzi said. “We need to treat pre-symptomatic individuals who are showing greater-than-normal amyloid build-up in their brains,” detected perhaps by imaging tests, he said.

Such an approach would require decades of treatment, an expensive and potentially risky endeavor if the therapy has even mild side effects that could emerge, or increase, over time, said Sam Gandy, associate director of the Mount Sinai Alzheimer’s Disease Research Center in New York.

“You may have to begin at 45 or 55, which would mean decades of exposure to a drug that may or may not be totally safe,” Gandy said. “My concern is it’s so early it will be difficult to target unless you have a drug that’s perfectly safe.”

Much is still unknown. There’s the question of whether the U.S. Food and Drug Administration would ever allow such a study to be conducted in patients without symptoms, who would need treatment for decades before any benefit emerges. And the question remains of how to test patients to find out which are most likely to develop dementia.

“The net is that all of the ongoing phase 3 programs that attempt to slow the progression of Alzheimer’s disease still appear to be very high-risk,” Tim Anderson, an analyst with Sanford C. Bernstein in New York, said in a note to clients. “This is why we continue to build no revenues in our forecasts.”

With assistance from Doni Bloomfield

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