The Alzheimer’s drug lecanemab wins full FDA approval. It’s a very big deal.
A proven treatment to slow down the progression of Alzheimer’s — a devastating disease that robs individuals of their personality, autonomy, and ultimately life — has long been out of reach.
But within the next year, Alzheimer’s patients could conceivably have access to not just one such treatment, but two.
This new era for Alzheimer’s treatment began this week, when the Food and Drug Administration granted full approval to a new Alzheimer’s drug, lecanemab, which is being sold by its manufacturer Eisai under the brand name Leqembi. Memory clinics are already reporting increasing curiosity among patients about the new treatment, and they expect interest will only grow following the FDA’s final sign-off.
In the next few weeks, new clinical trial results are also expected for another treatment candidate, donanemab, which has had impressive preliminary results.
Just two years ago, the Alzheimer’s community was in turmoil. An earlier drug, called aducanemab and known by the brand name Aduhelm, had reported disappointing clinical trial results, but the FDA, over the objections of its scientific advisers, still decided to grant “accelerated approval” to the drug, which has a lower threshold for approval and is reserved for drugs that address an unmet need. The controversy cast a pall over the medication, Medicare severely limited coverage, and few prescriptions were written for a treatment once hoped to be a breakthrough.
People who work in the field describe a community at war with itself, as some advocacy groups pushed for more access to aducanemab even as many clinicians remained unconvinced.
Lecanemab could offer a fresh start. The clinical data appears more promising. The FDA’s advisers endorsed it last month. The preliminary results from donanemab appear even more impressive, though they need to be confirmed in forthcoming reports.
It is still a fraught moment for providers and patients. The treatments require an extensive patient evaluation before being prescribed, regular infusions in their administration, and careful monitoring over time to catch potentially dangerous side effects — all a challenge for the US health system. Not enough doctors are trained in caring for patients with memory problems. There are not enough infusion centers. Medicare covers some of the scans that could be used to identify patients who may benefit from lecanemab, but not others.
The logistical challenges could be daunting, said Sanjeev Vaishnavi, a clinical neurologist at the Penn Memory Center who is helping to lead its planning efforts. The center sometimes has a months-long waiting list from patients who are seeking more specialized care than their primary care doctor is able to provide. If the demand for lecanemab is high, new patients could end up waiting for years — at which point, they may no longer benefit from the drug.
“I think the concern is, how can we deliver appropriate care to the right individuals in a timely manner?” Vaishnavi said, articulating his fear that patients could end up “stuck in a morass of bureaucracy.”
Nevertheless, he said, “it’s an exciting time.”
Alzheimer’s afflicts at least 6 million Americans. While only a subset may benefit from lecanemab, it holds enormous promise for those patients and their families — and for the many Alzheimer’s patients who will follow in the years to come, as the country’s population ages. This disease is distinct not only for its prevalence but also for the way it works. Over time, it wears away a person’s personality and sense of self. Ultimately, it is 100 percent fatal.
Science has searched for an effective treatment; for decades, potential breakthroughs would show promise and then flame out. The failures led some researchers in recent years to question the entire premise of most Alzheimer’s research, though lecanemab may prove to be a kind of validation of the amyloid hypothesis that has driven drug development.
Jason Karlawish, the co-director at the Penn Memory Center, described his colleagues, patients, and their families as “travelers who finally see they arrived at land after traversing a dangerous ocean.”
“I’d much rather be in this place than where things were two or three years ago,” he told me. “This is what we’ve been waiting for for decades.”
Lecanemab, the new Alzheimer’s drug approved by the FDA, explained
Lecanemab doesn’t cure Alzheimer’s disease. Patients will still decline — but not as quickly. For certain patients who are still in the early stages of the disease, the drug appears to slow down the loss of cognitive function, buying them months — and maybe more — of quality time with their families and loved ones.
This is a breakthrough that has eluded scientists for years. Still, exactly how long patients get will vary, and the longer-term effects remain unknown. A clinical trial of 1,800 patients, the results of which were released last September, found lecanemab slowed cognitive decline by on average of 27 percent over 18 months.
The goal is to slow down the speed of decline from mild cognitive impairment, usually the first recognized stage of Alzheimer’s disease, to dementia, the more advanced loss of cognitive function. Karlawish said he explains lecanemab’s effects to patients like this: 33 percent of the patients on a placebo transitioned to a more advanced stage of the disease during the 18-month study, but 22 percent of the patients on lecanemab did.
In the earlier stages of the disease, patients can still often seem and feel like themselves. In a recent conversation with Karlawish, the husband of a patient with Alzheimer’s had told him that, when describing his wife at her current stage, “Susan is still Susan.” (Susan is an alias.)
“For him, the idea of keeping Susan still Susan is pretty valuable,” Karlawish told me. “But some people will say to me, ‘My wife is not my wife anymore.’ I don’t know how they’d think of slowing down progression.”
That is the first qualifier for lecanemab: It will only help patients who are in that earlier “mild” stage of the disease. For people who have already progressed past that, the pending approval may be bittersweet. Attitudes among families are complex. Alison Lynn, a social worker at Penn who works with caregivers, said she recently spoke to a man who is both a physician and the husband of an Alzheimer’s patient. He said he would not want his wife to be prescribed the drug.
In his words, “both of us are suffering right now. Why would I want the suffering to last longer?” Lynn said. “I don’t think that is an easy thing for him to say.”
But even for patients for whom lecanemab may be appropriate, there are qualifiers. About one in five patients in the clinical trials experienced brain swelling or bleeding. In a few cases, the symptoms were severe and at least three deaths have been associated with it. Still, the FDA’s scientific advisers, who had previously decided the risks of aducanemab were not worth it, reached the opposite conclusion with lecanemab. Alzheimer’s disease is, after all, a terminal illness. Still, doctors will need to explain the risks to patients and watch for side effects.
In part because of that need, lecanemab will not be a simple drug to offer patients — and the demand unlocked by its FDA approval will only further strain health care providers. Full approval, as opposed to the accelerated approval granted to aducanemab, should lead to Medicare covering the drug more readily. But for every patient who walks through the door asking about lecanemab, there will be multiple steps to take before they are prescribed the drug — and another complex process to follow after their treatment begins.
What patients should know about getting prescribed lecanemab
For patients interested in lecanemab, the first step will be screening.
Primary care doctors could be helpful in identifying patients who are too impaired to qualify, Vaishnavi said. But they are generally not in a position to do the kind of intensive testing needed to distinguish normal cognitive aging from the mild cognitive impairment that would make a patient a candidate for lecanemab. Those people will often end up at a clinic like the Penn Memory Center.
After cognitive function tests, patients will need physical scans to make sure there is not another cause of their symptoms or a high risk of brain bleeds, and to identify the biological markers that the drug is designed to target, amyloid plaque. Penn will also administer genetic testing to identify patients who may be less likely to benefit and at higher risk of serious side effects.
For patients who are prescribed lecanemab, they will be back at the clinic regularly. Infusions are given every two weeks (with some leeway) and last for 30 to 60 minutes. For the first few infusions, patients may need to stay longer to monitor for any adverse effects.
They will also need to come in periodically for brain scans to make sure there are no signs of swelling or bleeding, as patients with side effects usually have no outward symptoms. On top of that, there will be some unknown number of unscheduled MRIs for patients who do experience some concerning symptoms on their own. For the patients who have side effects, they may need to pause treatment. Some might never be able to go back on the drug, but others could if further exams reveal their issues have stabilized or reversed.
It will be a logistical nightmare. Administrators will be playing a neverending game of scheduling Tetris. Vaishnavi said infusions can be moved up or back by a week, but that is about the extent of their flexibility. They can only guess how much demand they will see and, for the foreseeable future, they will be fielding most patients who want this drug, as specialized clinics are best outfitted to perform the infusions.
Down the road, the hope is that it will be easier for other clinics to administer lecanemab and, maybe someday, patients could be able to do it at home. But when this drug hits the market this summer, there is likely to be a bottleneck at clinics like Penn, because they are among the few who can appropriately provide it.
Even there, Vaishnavi said they could use more clinicians — doctors, physician assistants, and nurse practitioners — given how much work will go into monitoring for side effects. There will be additional administrative work for them, too, as Medicare will require providers to put their patients in a registry and report on the real-world outcomes they see.
“We don’t have the appropriate health care system for these drugs,” Karlawish said, warning there would be “a lot of bumps in the road.”
This pivotal moment for Alzheimer’s treatment promises both new hope for patients and a reality check for a health care system that continually struggles to make the most of novel medicines for diseases that affect millions of Americans.
“Everyone’s feeling excited by this,” Lynn said. “It’s exciting but fraught.”
Source: Vox.com
