A drug to slow Alzheimer’s is finally available. How are patients faring?

Over the last three years, a new class of Alzheimer's drug has set off a roller coaster of hope and disappointment. Illustration / Dadu Shin, The New York Times

Over the past three years, a new class of Alzheimer’s drug, the first to treat a root cause of the disease, has set off a roller coaster of hope and disappointment. But while these so-called anti-amyloid antibodies had a rough start, many patients and their doctors are feeling more optimistic now that one of the medications is finally being used more widely.

Lecanemab (brand name Leqembi; pronounced le-KEM-bee) was given full approval by the US Food and Drug Administration in July 2023 and is currently the only one of its class available to Alzheimer’s patients, outside clinical trials. The drug has been shown to slow the progression of the disease, but its benefits are fairly modest. It is also a burdensome therapy and has a high risk of troubling side effects.

With lecanemab having been approved for nearly a year — and with a similar drug, donanemab, recommended for approval by an FDA advisory committee at a meeting on Monday — The New York Times checked in with experts at three major medical centres about who’s receiving lecanemab and how they’re responding.

Who’s being prescribed lecanemab?

There are strict requirements for patients to be eligible for lecanemab; by one estimate, fewer than 20 per cent met the qualifications for the medication. Neurologists at the Mayo Clinic, Massachusetts General Hospital and the University of California, San Francisco, all described a similar review process when deciding which patients are good candidates.

First, the patient must be diagnosed with mild cognitive impairment or mild dementia, the earliest two stages of Alzheimer’s disease. Second, because lecanemab works by removing the amyloid plaques that are a hallmark of the disease, patients undergo a PET scan or a lumbar puncture to make sure plaques are actually present in the brain. Third, the patient needs an MRI to screen for signs of other brain diseases.

“We want to make sure that they don’t have another explanation for their cognitive problems,” said Dr Ronald Petersen, director of the Mayo Clinic Alzheimer’s Disease Research Center.

Brain scans from a patient in the clinical trials of donanemab show amyloid plaque being removed from the patient's brain. Image / Eli Lilly via The New York Times

Hospitals also require genetic testing for the APOE4 gene variant, because having two copies of it substantially raises the risk of severe side effects, most notably brain swelling and bleeding. Some medical centres automatically exclude patients with two copies of the gene; others allow it but will counsel the patient about the increased risks. Another reason not to give patients the drug is if they’re taking a blood thinner, which also raises the risk for serious brain bleeds.

Even if a patient meets all these criteria, doctors still may not prescribe lecanemab. The person may have other health issues or live far from a hospital with MRI, which is necessary to evaluate patients if they suddenly start experiencing severe side effects.

In each case, a panel of neurologists, radiologists, psychiatrists, geriatricians and other experts vote about whether they think the patient qualifies.

“It really is a multidisciplinary approach,” said Dr Gil Rabinovici, a professor of neurology at UCSF. “We think very carefully about every patient and make decisions ideally by consensus about who is eligible.” Since UCSF started administering lecanemab last fall, the hospital has treated a few dozen patients with it, with roughly 60 per cent of people who met the screening criteria ultimately being approved by the panel.

What does treatment entail, and what are the medication’s risks?

Eligible patients and their families have many things to weigh as well.

On a practical level, lecanemab can be time-consuming and expensive. Patients have to come in for infusions every two weeks, plus regular MRI scans to monitor for side effects. And while the drug is 80 per cent covered by Medicare, the treatment and the many doctor visits it requires can still add up to US$6600 (about NZ$10,770) annually in out-of-pocket expenses, according to one estimate.

“For them to travel, take one day off every two weeks” is a lot for patients and their family members, said Dr Liliana Ramirez Gomez, clinical director of the Memory Disorders Division at Massachusetts General Hospital.

People also need to consider the risks. The primary concern with lecanemab is a condition known as ARIA, for amyloid-related imaging abnormalities, which can cause brain swelling or bleeding. During one clinical trial, these side effects occurred in between 5 per cent and 39 per cent of patients, depending on the person’s APOE4 status, though it often showed no symptoms. Of more than 1600 patients who received a dose of lecanemab, four deaths were possibly connected to the medication.

There have been cases of ARIA at all three medical centres, but so far, none has been severe. “I don’t think the manifestation of the side effects have been as worrisome as some might have anticipated,” Petersen said.

What are the benefits, and how are initial patients responding?

Along with these risks and burdens, the potential benefit from taking lecanemab is, on average, a 27 per cent slowing of the disease. The drug won’t improve people’s memory, but it delays the progression of Alzheimer’s by about five months.

It helps people stay “at their current early phase for longer”, Rabinovici said. “It’s delaying the time when they need help with basic activities of daily living.”

Most of Rabinovici’s patients taking lecanemab have only been on it for a few months, so he said they’re still in “wait and see mode” to evaluate the benefits.

Despite their concerns, the experts said many of their patients — and their doctors — were enthusiastic about the medication.

“Alzheimer’s disease is a devastating condition for the patients, for their families, so people are actually very excited, eager to receive this treatment,” Ramirez Gomez said. “On the physician side, I think there is a sense of optimism, too, to a certain extent.”

That’s how Helene and her husband, Joseph, feel. When Helene was diagnosed with mild cognitive impairment due to early onset Alzheimer’s disease at 61, she and Joseph immediately starting looking for potential treatments and clinical trials. (Both asked to use middle names to protect their privacy.)

After completing all the required tests, they learned that Helene was a good candidate for lecanemab and decided to pursue treatment. While they have faced several hurdles — fighting to get Joseph’s insurance to cover it, travelling 90 minutes round-trip to the infusion centre, a bad reaction after the first dose — the process has been worth it. Helene hasn’t had any problems with brain swelling or bleeding, and she hasn’t progressed to the next stage of the disease.

“You have to take a leap of faith that the science is there,” Joseph said. “There’s risks, but we feel we’re managing those risks reasonably well.”

“From a selfish perspective,” he added, “I just want her longer.”

This article originally appeared in The New York Times.

Written by: Dana G. Smith

Illustration by: Dadu Shin

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