What Louisiana Patients Should Know About Alzheimer's Drugs | Louisiana Department of Health

After decades of failed clinical trials that offered no hope for Alzheimer's patients, a drug has emerged that shows some promise. Known as anti-amyloid antibodies, the drugs come with risks and are thought to only slow the deterioration of patients in the early stages of the disease, but they offer an option in a previously hopeless situation.

Lecanemab, also known by the brand name Rekembi, was approved by the Food and Drug Administration about a year ago. A second drug in its class, donanemab, sold under the brand name Xanla, was approved in July.

A year of field experience and the expectation of more options in the future have the field optimistic. There is still much to learn, the diagnostic process is complex and time-consuming, and many patients who could benefit are unaware of the drug's existence. Dr. Demetrius MaraganoaChair of the Department of Neurology at Tulane University.

“I think there's still a general lack of awareness in the community about what this treatment is and who it's for,” Maraganole said.

Who are good candidates?

Patients are subject to a rigorous vetting process: Because the drug is only approved for mild cognitive impairment or mild dementia, patients must have reached a certain stage of the disease — late enough that cognitive problems are noticeable, but not so late that the disease has progressed beyond the point where the drug can actually be effective.

Both drugs work by removing a protein called amyloid from the brain, which in moderate amounts has positive effects on the brain: It helps the nervous system grow, repairs leaks in the blood-brain barrier and is also a tumor suppressor, he said. Dr. James Rini, a neurologist at Ochsner Health.

But for reasons that are poorly understood, amyloid grows out of control in some people, clogging the brain's waste-clearance systems and building up in plaques that have long been the target of most Alzheimer's drugs.

Scientists once believed that the brain degeneration in Alzheimer's was caused by amyloid itself. Many now believe that amyloid is the first part of a chain of events that leads to degeneration. When damage to the brain is minor, drugs may help slow the degeneration. In many cases, amyloid formation is followed by inflammation and the formation of tau (another protein). At that point, the damage is too great for drugs to fix. Rini likens it to repairing a house after a hurricane.

“If you do repairs to your home before mold or water damage occurs, it can really make a difference,” Rini says, “and if you find out after the fact, it doesn't make any difference because you're already fixing the roof of a home where the infrastructure is crumbling.”

What is the process?

Maraganoa says the initial consultation to diagnose a patient takes about 90 minutes, which also includes cognitive testing. Other causes of cognitive decline, such as vascular dementia due to a stroke, must be ruled out with an MRI. Patients undergo blood tests to determine whether they have Alzheimer's, with 95% accuracy. Finally, they must undergo an amyloid PET scan or spinal fluid test to measure proteins and confirm the disease.

Locally, wait times can be as long as six months, Maraganoa said. Louisiana has only a few neurologists with the expertise to prescribe the drug, and about one in four people with Medicare who need to see a neurologist can get one, he said. The 2020 study was published in the journal NeurologyIt's a problem that will be exacerbated by an ageing population.

“Access to a neurologist is a challenge, both locally and nationally,” says Rini, who says her waiting list for new patients is about three months, but with general practitioners and other health care providers willing to order some of the tests, she can reduce the wait to about two weeks.

“Medicines only really work if they're caught early, so we're trying to respond as best we can,” Rini said. “The longer we wait, the less effective they're likely to be.”

Once deemed eligible, patients will receive an infusion every two weeks for 18 months and will need to undergo regular MRI scans to monitor for side effects.

What are the risks?

This treatment also has its drawbacks: Some patients may have to return twice a month for infusions, depending on where they live.

“Many patients forgo the opportunity to receive treatment because they don't want to travel to an infusion center to receive treatment or they don't have enough support or strength to receive treatment,” Maraganole said.

Cost is another barrier: For people over 65, Medicare pays 80% of the cost of treatment, which comes to about $28,500.

“For some seniors, 20 percent of $28,500 is still a lot of money,” Maraganoa said.

People under the age of 65 may have insurance that covers the cost of their medications, but it is not uncommon for doctors and patients to request coverage multiple times even when insurance covers them. Some hospitals offer financial assistance, and pharmaceutical companies may cover medications that are not covered by insurance.

Once patients start the infusion, the biggest risk is amyloid-related imaging abnormalities called ARIA, which come in two forms: edema, which is a buildup of fluid, and hemorrhage, which is small bleeding in the brain.

Ochsner reports that ARIA edema occurs in about 2 out of 50 patients. In clinical trials, about 12.5 percent of participants had edema, but most of them had no symptoms. In most people, the edema resolves on its own.

Rini said the plaques are like scar tissue, and removing them can cause symptoms similar to those caused by removing scar tissue from a burn on the skin.

“Just imagine what it would be like if you put it on your arm and then took it off,” Rini says. “It might sting a little, it might swell a little, it might bleed a little.”

In the trial, about 17.5 percent of participants experienced ARIA bleeding, a statistic that scares people but is misleading, Rini said: Even in the control group, who didn't receive the drug, 10 percent suffered brain hemorrhages.

Lini said two of his patients (about 4 percent) experienced brain hemorrhages, both of whom had other risk factors that made them more likely to suffer from the condition and continued taking the medication without symptoms.

Rini occasionally sees patients with symptoms that seem like allergic reactions, and typically prescribes anti-allergy medications like Benadryl and steroids. Some patients also develop headaches.

What are the benefits?

The drug has not been proven to improve memory, but it can slow disease progression: In clinical trials, patients who took lecanumab saw their disease progression slow by 27%.

“After 18 months of treatment, you're in the same position as if you hadn't been on treatment for 12 months,” Maraganoa said, “so it's like turning the clock back six months.”

Anecdotally, some patients find that stabilizing their disease improves their functioning: One of Rini's patients, in his late 70s, has reported improvement in his symptoms.

“The family has noticed that my mother is becoming more conscious with each passing day,” Lini said. “Specifically, my daughter contacted us a month ago and said, 'My mother's back.'”

A patient with early-onset Alzheimer's disease in his 50s said friends and family have told him he seems like his old self again.

“We've been very clear about our expectations with this drug: The goal here is not a cure. The goal here is to slow progression,” Rini said, “but we have some patients whose progression has slowed dramatically.”