Eisai Co.’s much-anticipated findings on its experimental Alzheimer’s drug provided tinder for a debate over whether its modest efficacy is worth potential risks that include serious brain bleeding.
Lecanemab, developed with help from Biogen Inc., cleared plaque that clogs patients’ brains and slowed their mental decline by 27% over 18 months. Yet the improvements came at the price of side effects like brain swelling and bleeding in more than one in five people on the medicine, compared to 10% of those who received a placebo.
The findings presented at the Clinical Trials on Alzheimer’s Disease conference in San Francisco may be good enough to propel the therapy into a market that RBC Capital Markets analysts say could eventually reach $10 billion. Lecanemab is the first drug designed to slow Alzheimer’s that has generated unambiguously positive results. While questions remain about how it will be used, the findings should be enough to give patients a therapeutic option for the inexorable disease, doctors and analysts said.
“It takes it out of the untreatable category,” said Stephen Salloway, a study investigator and neurology professor at Warren Alpert Medical School of Brown University, in an interview.
The detailed data generated “palpable physician enthusiasm” at the conference, according to RBC Capital Markets analysts led by Brian Abrahams. Benefits of the drug appeared strong in areas that would likely be important to regulators and doctors, they said in a note.
Biogen rose as much as 5.8% at the New York market open, its biggest intraday gain in six weeks. Eisai’s shares closed up 3.8% on Wednesday in Tokyo.
Two Deaths
Most cases of brain swelling and bleeding weren’t symptomatic, though patients sometimes had headaches, visual disturbances, confusion or worse. Five people given the drug developed large brain hemorrhages, compared to one in the placebo group, according to results published in the New England Journal of Medicine.
The report didn’t include two widely publicized deaths that occurred in the extension portion of the trial, when everyone was offered the drug.
Both patients had other health problems and were taking medications that may have contributed to bleeding in the brain or death, the company said. A 80-year-old man had a heart attack following a brain hemorrhage, while a 65-year-old woman began bleeding after taking the blood thinner tPA after a stroke, said Michael Irizarry, Eisai senior vice president of clinical research.
“It is Eisai’s assessment that the deaths cannot be attributed to lecanemab,” the company said.
In the main, placebo-controlled portion of the trial, no difference in death rates was found between those on the drug and those on a dummy treatment. A patient who received only placebo and had a hemorrhage also died, the company said.
Open Questions
One unanswered question hovering over the San Francisco meeting is why Eisai succeeded when similar drugs produced ambiguous or negative results. Both lecanemab and Roche Holding AG’s gantenerumab target amyloid, an abnormal protein in the brain linked to Alzheimer’s disease. Roche is slated to report detailed findings from two large, failed studies of its drug Wednesday at the conference.
It’s also not clear how widely the medicine should be used. The benefits appear modest and there will be debate about whether they are meaningful to patients, said Lon Schneider, a professor of psychiatry and neuroscience at the University of Southern California Keck School of Medicine.
While both groups continued to worsen during the study, lecanemab was associated with roughly half-a-point less decline on an 18-point rating scale that combines measures of cognition, memory and ability to perform daily activities. While the trial lasted only 18 months, the disease can play out over a decade or more.
The results do provide momentum for the field at large, said researcher Sharon Cohen, medical director and principal investigator at the Toronto Memory Program, at the CTAD meeting.
“It behooves us to continue to push these treatments forward,” she said. “These results really also ask us to focus on a paradigm shift of diagnosing earlier in order to achieve disease slowing and to extend milder stages of disease.”
Regulatory Review
The Alzheimer’s Association called for approval of the medicine, saying it will allow patients more time to live independently and participate in daily life.
“It could mean many months more of recognizing their spouse, children and grandchildren,” the group said in a statement. “Treatments that deliver tangible benefits to those living with mild cognitive impairment due to Alzheimer’s and early Alzheimer’s dementia are as valuable as treatments that extend the lives of those with other terminal diseases.”
The details will be pored over by regulators at the Food and Drug Administration and officials at the US Centers for Medicare and Medicaid Services. Medicare, the US health program for the elderly, all but rejected an earlier Alzheimer’s drug called Aduhelm from the two companies, only covering it for research purposes.
That drug’s accelerated US approval in 2021 was controversial because of conflicting efficacy results from two large trials. Biogen ended most of its marketing efforts after the payment restrictions.
Eisai requested accelerated US clearance based on lecanemab’s ability to lower amyloid, and the FDA is expected to make a decision by early January. If it’s approved, the company plans to rapidly submit the efficacy data from the trial in order to get full clearance. The hope is that a rapid airing of the data, warts and all, will convince Medicare to broadly cover lecanemab.
The agency is likely to grant accelerated approval in January, though initial sales may be slow, said Stephen Barker, an analyst at Jefferies in Tokyo, in a note to clients. If lecanemab’s superiority over placebo continues to grow over time, “prospects for widespread adoption will be given a boost, and patients that start therapy will have more incentive to stay on therapy longer,” he said.
Potential Pricing
The cost hasn’t yet been set for the medication, though an economic assessment conducted by Eisai using earlier stage studies yielded an estimated potential annual value-based price of $9,249 to $35,605.
How widely the drug will be used depends on the reimbursement decision from Medicare, which may take some time, Barker said. Most investors expect a price close to the $28,000 a year that Biogen and Eisai eventually settled on for Aduhelm, he said.
Other hurdles may complicate use of the medicine for at least a few years, including requirements such as scanning patients’ brains to determine their pre-treatment amyloid levels, said Takeshi Iwatsubo, a neuropathologist at the University of Tokyo’s Graduate School of Medicine.
“It’s a unique, complex drug that must be used by specialists,” he said in an interview. “But the number of dementia specialists and PET-scan facilities are limited, and capacity is a huge issue.”
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