The news Tuesday night that a clinical trial of an experimental Alzheimer’s therapy had succeeded hit like a blast — at last, a rare win in a disease devastating nearly 6 million Americans and countless more caregivers.
The trumpeting from the companies Eisai and Biogen relied on data that showed that people receiving the therapy, lecanemab, saw a slower decline versus those on a placebo. That finding was based on a .45-point difference between the groups on an 18-point scale called the Clinical Dementia Rating sum of boxes, amounting to a 27% reduction in the rate of cognitive decline.
But translating what that statistical gobbledygook could mean for patients living with Alzheimer’s is a different challenge, one that physicians will have to navigate as they weigh whether to prescribe the treatment (presuming it wins regulatory approval) and for which patients.
Doctors who spoke with STAT noted they were at this point relying on company press releases about the trial. The full data have yet to be presented and published.
Still, some did not foresee much meaningful change in patients’ lives.
Victor Henderson, a neurologist at Stanford, said he thought a not-even-half-point difference between patients who received lecanemab and those who got placebo was “probably too small to be noticed by patients and their families.”
While he was waiting for the full data, “I wish I could be more impressed than I am at this point,” said Henderson, who has previously advised the Institute for Clinical and Economic Review, a nonprofit that estimates the value of new medicines.
Others were more heartened. Babak Tousi, a neurogeriatrician at the Cleveland Clinic, said people with early Alzheimer’s might typically decline one to two points on the scale over 18 months, which was the duration of the trial. Staving off half a point of decline could mean “more days of independence compared to more days requiring more assistance,” said Tousi, who was an investigator in the trial and who has consulted for Eisai and Biogen.
The clinical significance of the trial data — as opposed to the statistical significance, which was proven by the study — will continue to be debated among neurologists and geriatricians as lecanemab moves through the regulatory approval process and into doctors’ offices. Insurers could also weigh in, assessing how widely they’re willing to cover the treatment and for which patients based on what kind of perceptible outcomes they think the data point to.
After all, what people want from any Alzheimer’s therapy is not measured by some “sum of boxes” or questionnaire but by the details of an individual life. Would this mean they could keep driving or working? Could they keep taking the dog for a walk without their family worrying about them getting lost? Could they hold on to the knowledge of who those family members are — and who they themselves are — for longer?
The CDR-SB scale used in the trial incorporates six cognitive metrics, including memory, problem solving, and personal care. Higher scores on the 18-point scale indicate more advanced dementia.
Mia Yang, a geriatrician at Wake Forest, noted that the impact of a .45-point difference on the scale depended on where someone was. Someone with a CDR score of 0.5, for example, might have some memory problems but could still keep up with daily activities. Someone with a score of 1, however, might start encountering some functional losses.
A half-point difference wouldn’t mean much for someone with more advanced Alzheimer’s, Yang said.
“I’m cautiously optimistic that it could be potentially meaningful for those folks who are in the mild stage,” Yang said about lecanemab. Indeed, the trial focused on people with early-stage Alzheimer’s.
Judy Heidebrink, a neurologist at the University of Michigan, said she wanted to see how the CDR scores changed over time for the placebo group versus the treatment group. That way, she could explain to patients and their families that the point to which an average participant declined after, say, six months without lecanemab wouldn’t be reached for, say, nine months with treatment. That could be more useful than trying to explain what a 27% reduction in the rate of cognitive decline means for them.
Heidebrink, who has been involved in other trials of lecanemab and has run other Alzheimer’s treatment trials, also said that doctors will need to consider the downsides and hurdles associated with the medication when deciding whether to recommend it for a particular patient. There could be costs that come with getting the therapy, which is given twice a month via infusion. About 1 in 5 patients who received lecanemab in the trial experienced brain swelling or bleeding, though less than 3% of them had symptoms.
“That’s where putting the benefit into context is trickier,” Heidebrink said.
In talking with patients and their families about lecanemab, doctors will also have to communicate that the treatment won’t halt their decline, and it certainly won’t make them better. Rather, the data indicate that lecanemab just slows what will still be irreversible cognitive and functional losses.
Marsel Mesulam, the director of Northwestern’s Center for Cognitive Neurology and Alzheimer’s Disease, said there was nothing doctors wanted more than having a clearly effective Alzheimer’s treatment. But he said he was also leery about what could happen if there’s an expensive drug that comes with serious side effects and has a limited clinical benefit.
If that’s the case with lecanemab, Mesulam said, it could lead doctors to do some “soul searching about whether you would recommend this, or not recommend this.”
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