Chicago. The first breakthrough in 30 years of Alzheimer’s research is boosting clinical trials of “cocktail” treatments that target the two distinctive proteins associated with the mind-disturbing disease, according to interviews with researchers and pharmaceutical executives.
Drugmakers Eisai Co Ltd and Biogen reported in September that their lecanemab therapy could slow disease progression by 27 percent over 18 months compared with a placebo.
The finding validates the theory that removing the amyloid protein that forms clumps in the brains of Alzheimer’s patients could slow or stop the disease and has strengthened support from some scientists for simultaneously targeting another notorious protein: tau.
Eisai and Biogen are scheduled to present the full data from their lecanemab study Tuesday at the Alzheimer’s Disease Clinical Trials conference in San Francisco. In addition, the US Food and Drug Administration is expected to make a decision in early January on the companies’ request for expedited approval.
If approved on an expedited basis, the companies said they would immediately seek full regulatory approval in the United States, which could help secure Medicare coverage.
“I think lecanemab has reinvigorated the idea that you can now do a combination of amyloid (and) tau,” Dr. Reisa Sperling, a neurologist and Alzheimer’s researcher at Harvard Medical School, said in an interview.
Tau accumulates naturally in a memory center in the brain called the medial temporal lobe as people age. A growing body of research suggests that the rise in amyloid in Alzheimer’s patients acts as an accelerator, triggering an explosive spread of tau that forms toxic tangles inside brain cells, eventually killing them.
“We’ve been trying to do combination testing for years,” Sperling said. Nearly a decade ago, Alzheimer’s experts met in Washington to discuss the trial of combination therapies. At the time, “nobody wanted to listen,” he recalled.
Now, however, Sperling and other researchers from the Alzheimer’s Clinical Trials Consortium (ACTC), a research network backed by the National Institute on Aging, say drugmakers are increasingly interested in participating in a study. to test anti-tau drugs alone and in combination with anti-amyloid drugs, such as lecanemab.
“We’ve talked to a number of companies about collaborating with us on our proposed platform, which can test multiple drugs, and everyone is interested,” said Paul Aisen, MD, director of the Alzheimer’s Therapeutics Research Institute at Keck School of Medicine. from the University of Southern California, and leader, along with Sperling, of the ACTC.
The scientists said they expect an answer on funding by the end of the year. The NIH says it’s not talking about the grants under review. More than 6 million Americans have Alzheimer’s, costing the US economy nearly $6 billion a year in out-of-pocket costs and unpaid expenses from caregivers, according to congressional documents. By 2050, Alzheimer’s cases are expected to double to 12.7 million, bringing the total annual cost to nearly $1 trillion, according to the documents.
Last year, the FDA granted Biogen and Eisai’s aducanumab conditional approval even though it failed in one of its two late-stage trials. The approval was based on the drug’s ability to clear amyloid from the brain.
Biogen initially priced the drug at $56,000 a year, but the US Centers for Medicare & Medicaid Services said it needed more convincing evidence and that Medicare would only cover the drug for use in clinical trials.
Lecanemab’s success is based on years of research into the causes of Alzheimer’s, as well as advances in measuring amyloid deposits using brain scans and spinal fluids. Trials of anti-tau drugs will build on those advances, using brain scans, spinal fluids, and blood tests to better assess the stage of the disease, when to intervene, and whether the drug is hitting its target. This would allow companies to test drugs even before symptoms appear.
Nearly a dozen drugmakers, including Roche, Merck & Co, Johnson & Johnson, and Eli Lilly and Co, are working on tau-targeted therapies. At least 16 treatments are being tested in clinical trials, with results expected in the next three years, according to a Reuters review of the registry of clinicaltrials.gov.
Merck is testing its MK-2214 therapy, aimed at knocking out tau in patients at very early stages of the disease, in several small trials.
“Understanding of the disease is getting much, much better,” said Jason Uslaner, head of neuroscience discovery at Merck. The drugmaker has been largely absent from the Alzheimer’s scene after the high-profile failure of its drug verubecestat five years ago.
So far, only a few trials combine an amyloid-lowering therapy with a tau-targeting drug in a “cocktail” approach, similar to those used against cancer and HIV.
The combinations could enhance the benefit of reducing amyloid alone in people who have symptoms, the researchers told Reuters. And if used early in the disease, it is hoped that they can prevent dementia altogether.
“It is possible that both are needed – the removal of the amyloid that drives the biological cascade – and the cleanup of the tau that is already spreading from one cell to another,” said Dr. Adam Boxer, a tau expert at the Memory Center. and Aging from the University of California San Francisco (UCSF).
But several antibody therapies from Lilly, Biogen and AbbVie designed to slow the rate of tau buildup failed miserably last year. One Roche drug, semorinemab, showed limited efficacy.
“It took 20 to 30 years before we found a drug that actually targets the right form of amyloid to make a difference,” Boxer said. “It’s still early.”
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