Efforts to find treatments for Alzheimer's disease suffered blows in recent days, but many companies, scientists and investors are still optimistic that they can find a way to treat the memory-robbing disease, which affects roughly 5.5 million Americans.
Axovant Sciences Ltd. on Monday shuttered development for a once-promising Alzheimer's drug, an announcement that came days after Pfizer Inc. said it was giving up on the space entirely.
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"The mood is definitely negative on anything near-term, [but] there continues to be interest in this space," said Mark Ginestro, a principal for health-care and life sciences strategy at KPMG in San Francisco. "It's too big of a market to ignore. People are going to continue to go after it despite the roadblocks."
Roche Holding AG, Biogen Inc., Eli Lilly & Co. and others are still developing therapies. Startups with neuroscience pipelines, like Denali Therapeutics Inc. and Verge Genomics, are attracting funding, and so are early-stage research projects.
During the fiscal year 2017, the National Institutes of Health will have poured an estimated $1.35 billion into Alzheimer's disease, almost triple its investment for fiscal year 2013. And Pfizer said it had plans to establish a corporate venture fund focused on neuroscience projects.
Sales of successful treatments for the disorder could amount to billions of dollars as demand for therapies increase due to an aging population. Analysts had predicted that annual sales for Axovant's drug, known as intepirdine, could have topped $2 billion.
"It's too early to give up," said Paul Aisen, the director of the University of Southern California's Alzheimer's Therapeutic Research Institute in San Diego. "We're actually on the precipice of major advances. I would not discount all the disappointments over the years, but I believe we're in good shape."
The recent failures that have plagued the pharmaceutical industry and brewed much frustration among investors have been the result of a suboptimal approach to drug development, Dr. Aisen said. For years, the industry has focused on dementia, which happens at the latest stages of the disease, when reversing the damage done to the brain is difficult, if not impossible, he said.
Many of the drugs that have failed in large clinical trials have targeted beta amyloid, the sticky plaque in the brains of Alzheimer's patients that many scientists believe is a leading cause of the disease. But attacking these plaques in the brain didn't affect cognition.
Companies and researchers pursuing treatments are still pursuing amyloid in many cases, but they are beginning to focus on treating patients earlier in the disease process, before they show memory deficits or cognitive decline. New neuroimaging technologies, genetics and more sensitive cognitive tests are also helping clinicians to better understand how the disease progresses, and to potentially identify patients who could benefit from treatment before cognitive symptoms appear.
In some cases, patients are identified based on genetic testing that suggests they might be at a higher risk of developing the disease. Others have amyloid plaques, but don't yet have cognitive deficits.
Lilly's amyloid-targeted drug, solanezumab, failed to benefit patients in several large and costly studies in patients with mild to moderate disease. After the failure of one study in late 2016, Lilly said it had spent nearly $1 billion on the experimental drug, and about $3 billion total on Alzheimer's research over the past three decades.
But Lilly continues to test solanezumab in other human studies, including one funded by the U.S. government testing the drug in at-risk patients who don't yet have outward signs of the disease.
Merck & Co. last year stopped a clinical trial of an experimental Alzheimer's drug, verubecestat, because it wasn't helping patients with mild to moderate forms of the disease. The drug, a BACE inhibitor, aimed to prevent an enzyme from producing the sticky amyloid.
Merck said it would continue a separate study of verubecestat in patients at an earlier stage of Alzheimer's known as prodromal. Results from that study are expected in 2019.
"The question is, how early is early enough?" Roger Perlmutter, Merck's head of research and development, said in an interview. "None of this is easy...we recognize this is one of the hardest drug-development areas," he said, adding, "we simply do not believe it is acceptable to stand on the sidelines."
Biogen is currently testing another antibody that goes after amyloid possibly by stimulating microglia, the brain's scavenger cells, to chew up the plaques. In a recent study, higher doses of the drug, known as aducanumab, cleared more plaques, but adverse effects were more common. The drug slowed cognitive decline in patients with early Alzheimer's. Some scientists say that the drug could cause inflammation in the long-term, which would be detrimental to brain health. Results for larger trials are expected in 2020.
Merck and other companies have also focused attacks on a different protein, tau, that forms twisted proteins in the brains of Alzheimer's patients.
That approach suffered disappointment in 2016, when a closely watched trial of a tau-targeted drug developed by TauRx Pharmaceuticals Ltd. failed to improve patients' cognition or daily functioning in a clinical trial.
Even if companies can figure out how to reach patients earlier in the process, success may not be as simple as targeting one protein or another, scientists say. Some believe an interaction between beta amyloid and tau plays a central role in the disease. Others think there are many possible triggers, including some beyond beta amyloid or tau.
Combination therapies targeting several Alzheimer's-related proteins, like amyloid and tau, could be more fruitful. Biogen and Lilly said such multifaceted treatments are likely the future of Alzheimer's therapeutics.
Axovant's drug, intepirdine, inhibited signaling pathways in the brain. Scientists thought that it could help with cognitive decline. Other attempts at developing similar drugs have also failed.
Some companies are looking for treatments in the cutting-edge field of gene therapy, which introduces beneficial genes to the body to help fight disease.
Johnson & Johnson last week announced a collaboration with the University of Pennsylvania aimed at inserting certain genes into harmless viruses that would carry the genes to the cells. The genes would then instruct the cells to secrete beneficial antibodies that would fight Alzheimer's.
Once injected into the body, the viruses ideally would be able to cross the blood-brain barrier, which separates brain tissue from the rest of the body, Eric Schaeffer, senior director of neuroscience innovation at Johnson & Johnson, said in an interview. The research is at an early stage and could be four or five years away from human studies, he said.
Denali Therapeutics, a San Francisco-based biotech company that has multiple Alzheimer's treatments in its pipeline, went public last month. The company has three Alzheimer's drugs in preclinical development targeting tau and other mechanisms, according to its website. Denali also announced last week it is working with Japan's Takeda Pharmaceutical Co. to focus on neurodegenerative diseases like Alzheimer's.
Given the huge unmet need in Alzheimer's, there are incentives to try to make headway in the market, according to Ritu Baral, senior biotech analyst for Cowen. Big pharmaceutical companies tend to be more conservative, she said.
"Small to midcap biotechs are inherently [willing to be] riskier," she said. "Everything is an investment for the future."
--Peter Loftus contributed to this article.
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(END) Dow Jones Newswires
January 08, 2018 19:42 ET (00:42 GMT)