Who Should Take Leqembi (lecanemab) for Dementia?

Have you read the headlines about Leqembi? They’ve been hard to miss! The New York Times announced: “New Federal Decisions Make Alzheimer’s Drug Leqembi Widely Accessible.” The Washington Post offered: “For Alzheimer’s patients, a new era of treatment brings hope and risk.” The questions most people want answered are: 1) How effective is this drug? And 2) Who is a candidate to take Leqembi? 3) Will Medicare and insurance companies pay the big bills?

Who Could Benefit from Leqembi?

Almost everyone knows someone who has suffered from dementia. It may have been grandpa, mom or cousin Charlie. If not a family member, then a friend or someone in a friend’s family has had to deal with Alzheimer’s disease (AD).

It is estimated that 6.7 million Americans over 65 are now living with AD. A few years ago, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) estimated that, worldwide, dementia would go from 57 million people in 2019 to 152.8 million in 2050 (Lancet Public Health, Jan. 6, 2022).

To say we are facing a horrifying pandemic would be putting it mildly. AD robs people of their memories, their families, their personalities, their livelihood, their quality of life and their wealth.

AD is horrendous for the victims, but this disease also takes a terrible toll on family and friends. Watching a loved one slip away is a nightmare. We need effective treatments now! Is Leqembi the answer?

A Short History of Lecanemab (Leqembi) and Friends:

Lecanemab is just one of the most recent monoclonal antibodies (MABs) developed to rid the brain of amyloid beta (Aβ) plaque. For decades, researchers have blamed this peptide for causing Alzheimer’s disease. The solution was thought to be anti-amyloid monoclonal antibodies (aka anti-Aβ mabs).

An article in Nature Reviews Drug Discovery (April 5, 2019) describes a long list of failures.  The author provides a:

“Select list of failed phase III trials based on the amyloid hypothesis of Alzheimer disease”:

Aducanumab
Solanezumab
Bapineuzumab
Immunoglobulin
Lanabecestat
Atabecestat
Verubecestat
Semagacestat
Tarenflurbil

The reason all these drugs failed was “lack of efficacy,” “toxicity,” or “toxicity and lack of efficacy.” Billions were spent trying to find an anti-amyloid drug that worked.

The author concludes that:

“Some drug hunters still have hope that anti-amyloids will deliver, either in earlier disease settings or with better-optimized properties…

“Others are increasingly calling for the exploration of alternative treatment strategies. These include tau-modulating drugs, microglia-targeted candidates and infectious disease-related agents.”

If you would like to read about alternate treatment strategies, here is a link to an article I wrote about viral infections and dementia.

There is another analysis of anti-Aβ mabs and Alzheimer’s disease (Frontiers in Aging Neuroscience, April 12, 2022).

It concludes:

“Amyloid hypothesis is considered to be related to the etiology of AD, but nearly all pharmaceutical therapies targeting Aβ have failed in the clinic during the past about 20 years, indicating that the pathogenesis of AD is quite complex and should be multifactorial. Despite many problems regarding immunotherapy for AD and these knowledge gaps in the pathogenesis of AD, the studies have still progressed in developing more anti-Aβ mabs for the treatment of AD.”

An Update on Leqembi Against AD:

The FDA initially gave lecanemab provisional approval in January 2023. The makers, Biogen and Eisai, had utilized the agency’s Accelerated Approval pathway. This is an option that uses a “surrogate endpoint” instead of clear clinical benefit as the criterion for a worthwhile medication.

In this case, Leqembi demonstrated the ability to reduce beta-amyloid plaque in the brains of people with Alzheimer’s disease. This buildup of sticky proteins is thought to contribute to the pathology of dementia.

The FDA announced that it was converting Leqembi from “accelerated” approval to “traditional” approval on July 6, 2023. This means that the drug will be partially paid for by Medicare and possibly many insurance companies. At $26,500 a year, that could be a game changer.

The Benefits of Leqembi:

When a new drug becomes available, it makes sense to look at what is known of the benefits and risks. People with AD and family members of people with AD want to know if Leqembi will reverse the inevitable cognitive decline.

The answer seems to be no. The drug is not a cure for dementia, and it doesn’t help forgetful people turn back the clock to the time when they could drive safely or work productively. We don’t know yet if they will stay out of nursing homes any longer.

The benefits of Leqembi are that it modestly slows cognitive decline from Alzheimer’s disease, so that people on the drug were doing a bit better than those on placebo at the end of the 18-month trial.

A Quick Summary of the Leqembi Data:

You can read about the actual data at this link.  Here is a very quick and dirty overview based on data published in the New England Journal of Medicine, Jan. 5, 2023:

The researchers used an 18-point measurement scale to monitor cognitive decline. It’s called the CDR-SB (Clinical Dementia Rating Sum of Boxes) assessment tool.

Follow this closely please: 0 = no cognitive decline! 18 is really bad Alzheimer’s disease. We’re talking the worst possible cognitive decline. The patients who participated in this clinical trial averaged a CDR-SB score of 3.2 at the start of the study. That means they all had “early Alzheimer’s disease.”

After 18 months, the volunteers getting the placebo had declined from 3.2 to an average of 4.86 out of a possible 18 points. Those on Leqembi declined to 4.41 out of a possible 18 points.

In other words, the test score of the people on placebo got worse by 1.66 points over 18 months. The people getting Leqembi got worse by 1.21 points. The net “benefit” was 0.45 points on an 18-point scale. Keep in mind, everyone declined. There was no overall improvement…just a bit less descent into Alzheimer’s disease. How the patients on lecanemab will do at 2 years or 5 years is not yet known.

The Risks of Leqembi:

There are risks associated with this drug, however. Some people experience brain swelling that shows up on MRI scans. Roughly 13% of those on lecanemab developed this adverse reaction during the clinical trial. Occasionally, such swelling produces headaches, dizziness, confusion, nausea, vision changes or seizures.

Sometimes the swelling may be accompanied by bleeding. We have been told that 17% of those on Leqembi developed this serious adverse reaction.

The black box warning notes that:

“Serious intracerebral hemorrhages, some of which have been fatal, have been observed in patients treated with this class of medications.”

Brain Shrinkage?

Another side effect that worries us has not shown up in news articles about this drug approval. The official prescribing information is also silent on this matter.

A study published in the journal Neurology (March 27, 2023) reports that such medicines may lead to brain shrinkage. Researchers call such shrinkage brain atrophy. It appears to be related to many of the drugs in this anti-amyloid category.

According to the investigators, anti-amyloid therapies may:

“…compromise long-term brain health by accelerating brain atrophy…”

We hope that the FDA and pharmaceutical manufacturers will be following up on this very important concern. Brain shrinkage does not sound like a good long-term outcome, especially for people whose brains are already compromised.

What Comes Next for Leqembi?

Billions of dollars have been spent developing anti-amyloid drugs. Until the approval of Leqembi, however, there was little evidence that this approach would result in the kinds of changes that most families are seeking.

It is estimated that about 1 to 2 million patients could be eligible for Leqembi. Over 5 million will not be candidates because their AD has advanced beyond meaningful help.

This is an IV drug. It will have to be administered as an infusion in a medical facility. Patients will have to undergo brain imaging, a sophisticated blood test or a lumbar puncture of the spine to determine that they have amyloid beta plaque in their brains.

Who Will Pay for Leqembi?

Medicare (thanks to taxpayers) will cover much of the $26,500 annual cost. There could be a big co-pay, though. People without supplemental insurance might have to kick in over $6,000 and that does not include the co-pay for scans and other costs. Depending upon the insurance policy, patients might have to spend several thousand dollars out of pocket. Remember, Medicare is us. We will all be paying for lecanemab infusions.

Final Words:

It remains to be seen what the long-term benefits of this new medication will prove to be. Families want to keep their loved ones out of nursing homes for as long as possible. We hope that Leqembi and other anti-amyloid drugs under development will provide this kind of meaningful clinical outcome. Only time will tell.

What do you think? Is a reduction in decline of 0.45 points on an 18-point scale over 18 months meaningful to you? Do you think this is a good investment by Medicare? Share your thoughts about Leqembi in the comment section below. Please share your own story about Alzheimer’s disease. Do you know someone who has suffered from dementia? What was it like?