Promising results from a trial of an experimental drug for Alzheimer’s made by Biogen and its Japanese partner Eisai are reviving hopes that an effective treatment for the devastating condition that’s long baffled the medical world may finally be at hand.
In what some researchers are calling the biggest advance ever in treating Alzheimer’s, the companies reported late Tuesday that the drug, called lecanemab, appeared to slow the progress of the debilitating illness more significantly than any of its predecessors.
The results come a year after the commercial failure of the two companies’ first Alzheimer’s medicine cast a pall over Cambridge-based Biogen’s future and sowed further doubt over a leading theory of the disease. Now, with the prospect of approval for lecanemab coming in as soon as a few months, the two companies have a second shot at a multibillion-dollar drug.
In a clinical trial of nearly 1,800 people with mild cognitive impairment or mild dementia, lecanemab was able to slow the decline in their conditions by 27 percent, compared with a placebo.
“This is really the first conclusive proof that there’s a way to change the course of the disease,” said Dr. Randall J. Bateman, a neurologist at Washington University School of Medicine in St. Louis. “This is going to have more impact on more patients than almost any other discovery I can think of.”
Importantly, like other available treatments, lecanemab does not cure, reverse, or even halt the memory-robbing disease. However, it adds important new information to the long-running debate within the medical world about the cause of Alzheimer’s and how best to treat it. A large body of research points to a sticky protein called amyloid that accumulates in the brain as a primary suspect. But until the lecanemab results, other drugs that targeted this accumulation either failed to remove the amyloid or to convincingly slow progression of the disease.
“I was absolutely thrilled,” Dr. Dennis Selkoe, codirector of the Center for Neurologic Diseases at Brigham and Women’s Hospital. “Having worked in the Alzheimer’s field for 40-plus years, I recognized this right away as the real thing.”
But Selkoe also acknowledged that removing amyloid is not enough to stop the disease, especially if there are already noticeable symptoms. He and other researchers envision a future when amyloid-lowering drugs are but one of a regimen of treatments to combat the condition. The results of advanced clinical studies of two more amyloid-reducing therapies are expected later this year from Roche, and early next year from Eli Lilly and Co.
“Lecanemab clearly reduces amyloid on the brain scans, there’s no question about that,” said Dr. Brian Silver, interim chair of the department of neurology at UMass Memorial Medical Center. “But it’s clear from this study that simply targeting amyloid is not going to be enough.”
Alzheimer’s is estimated to afflict more than 6 million people in the United States. An effective medicine for the disease would likely become a multibillion-dollar seller. That very opportunity eluded Biogen once before, as its first Alzheimer’s therapy, Aduhelm, was approved by the Food and Drug Administration in 2021, but was rejected by many doctors, hospitals, and insurers over concerns about its effectiveness,, safety, and initial price tag of $56,000 a year.
Analysts estimate lecanemab could generate sales of $8 billion a year, with Biogen splitting the profits with Eisai. Still, some experts caution that its effects are modest: on an 18-point scale of cognitive decline, lecanemab slowed the progression by just 0.45 points.
“This is not a home run yet, but it’s a solid double,” said Dr. Reisa Sperling, director of the Center for Alzheimer Research and Treatment at Brigham and Women’s Hospital. She was hoping the trial results would be “very clear, not controversial, and not requiring lots of explanation.”
By that metric, lecanemab is, so far, passing with flying colors, especially compared with Aduhelm. The earlier Biogen medicine modestly slowed cognitive decline by 22 percent in one study, but didn’t have a significant effect in a second study. When the FDA granted it an accelerated approval based solely on its ability to lower amyloid accumulation, many hospitals, including Mass General Brigham, declined to offer it to patients. Ultimately, Aduhelm barely generated any sales, forcing Biogen to resort to layoffs and other cost cutting.
Despite the fiasco, Biogen and Eisai are also asking the FDA for an accelerated approval of lecanemab, which could come as soon as January. They also plan to submit the therapy for a full approval by the end of March. The FDA could take the rest of 2023 to make its decision, but the lengthier approval process might be crucial for convincing insurers to pay for the drug.
Dr. Richard Dupee, chief of geriatrics at Tufts Medical Center, expects the FDA will grant approval, although he cautions against being “too optimistic,” since the drug will likely carry a high price relative to its marginal benefit. “I’ve cared for so many Alzheimer’s patients over the years, and I understand the agony that families go through,” he said. “So anything that might help to slow this thing down makes sense.”
Hugh Courtney, 59, a Concord resident who was part of the lecanemab study, was happy to hear about the positive results. Courtney is an accomplished economist and former dean of the D’Amore-McKim School of Business at Northeastern University, where he continued to teach until retiring in 2021 when symptoms of the disease made working too difficult.
For 18 months, Courtney went to McLean Hospital every two weeks for a 72-minute infusion, but doesn’t know if he got the drug or a placebo. However, since August he has been getting lecanemab for free as part of an extended phase. He said it’s hard to know if the drug is working.
“There isn’t any obvious change,” Courtney said. “But anyone who thinks this will just turn the switch to make everything perfect is not being realistic.”
Experts say it is possible for tests to indicate that the drug is slowing the disease, but not necessarily at a rate that’s obvious to patients and their families. “I’m extremely confident in the statistical significance, but the thing that will always be debated, as it should, is the clinical meaningfulness,” said Dr. Christopher H. van Dyck, director of the Alzheimer’s Disease Research Unit at Yale School of Medicine.
Slowing cognitive decline in the early stages of the disease might allow people to perform daily activities — such as driving a car, helping with finances, and using appliances — a few months longer, he added. “So I think every bit of slowing decline is important.”
Dr. Stephen Salloway, who oversees neurology and the Memory and Aging Program at Butler Hospital in Providence, one of the lecanemab trial sites, was particularly pleased that lecanemab appeared safer than Aduhelm. Both drugs can cause irregularities on MRI scans that might indicate brain swelling or tiny hemorrhages.
For Aduhelm, Salloway previously reported that signs of brain swelling were present in about 35 percent of recipients in trials. In the lecanemab study, doctors detected signs of swelling in less than 13 percent of drug recipients. Although that was encouraging, Salloway cautioned that “serious cases” can still occur. Signs of tiny hemorrhages were detected in 17 percent of people who got lecanemab, compared with 19 percent of people who received Aduhelm.
Betsy McAlister Groves, 73, a retired clinical social worker who lives in Cambridge, was encouraged by the positive results. Groves was diagnosed with early-stage Alzhiemer’s disease soon after Aduhelm’s approval. But reports of potentially severe side effects left her worried about taking that drug. To her, lecanemab “seems more promising and less risky.”
“It’s not a cure, but from this vantage point, anything that is marching in that direction would be helpful,” she said. “And I would be more than willing to take the drug.”
The lecanemab study provided a much-needed win for Biogen, which has suffered financial losses, instituted large layoffs, and announced the departure of its chief executive following Aduhelm’s failed rollout. Biogen’s stock shot up 40 percent on Wednesday, and Eisai’s rose 60 percent, although neither company’s value is near the highs following Aduhelm’s approval.
Lecanemab’s approval could send Biogen into a hiring spree to rebuild the Alzheimer’s sales division that it dismantled after insurance companies and Medicare refused to pay for Aduhelm.
If lecanemab is approved, Salloway hopes that Biogen and Eisai will charge less for it than Aduhelm’s list price. “I hope they’ll propose a price that’s reasonable,” he said.
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