Kisunla (Donanemab): Breakthrough or Boondoggle Against Alzheimer’s?

Two years ago we asked the question: Aduhelm for Alzheimer’s: Breatkthrough or Boondoggle? That was when the FDA announced it was approving aducanumab “…for the treatment of Alzheimer’s, a debilitating disease affecting 6.2 million Americans.” Biogen later abandoned Aduhelm to focus on a similar drug, Leqembi.  On July 2, 2024 the FDA announced it “…has approved Kisunla (donanemab-azbt) injection for the treatment of Alzheimer’s disease.” We are asking the same question as before, but two years later. Is the latest anti-amyloid treatment for Alzheimer’s disease (AD) a breakthrough or a boondoggle?

The Headlines Are Making FDA’s Approval of Kisunla Seem Exciting:

The Alzheimer’s Association, (July 2, 2024) announced:

“Alzheimer’s Association Welcomes U.S. FDA Approval of Kisunla (Donanemab)”

Contract Pharma (July 3, 2024) wrote:

“Lilly’s Kisunla Approved to Treat Early Alzheimer’s Disease 

“Trial participants treated with Kisunla had up to a 39% lower risk of progressing to the next clinical stage of disease than those taking placebo”

Seeking Alpha (July 3, 2024) makes the drug sound appealing:

“Eli Lilly Advances Alzheimer’s Solutions With Kisunla Approval”

The Washington Post was a little less exuberant (July 2, 2024):

“FDA approves Eli Lilly Alzheimer’s drug after months of delay 

“The agency determined that the potential of slowing the devastating disease in patients with mild cognitive impairment outweigh the risk of brain bleeds.”

Digging Just Below the Headlines About Kisunla (Pronounced kih-SUHN-lah):

Let’s get one thing straight from the get-go. Donanemab is not a cure for Alzheimer’s disease. No one is suggesting that it is, but over 6 million AD patients and their families are craving something that will reverse their cognitive decline. Kisunla will not do that. What it will do is modestly slow the decline of this form of dementia.

That may sound good to the FDA, the Alzheimer’s Association and to neurologists who have very little to offer AD patients at this time. But before civilians get too excited, here is some inside information.

Let’s start with the positive spin from Lilly (July 2, 2024):

“Kisunla slowed cognitive and functional decline by up to 35% compared to placebo at 18 months in its pivotal Phase 3 study and reduced participants’ risk of progressing to the next clinical stage of disease by up to 39%”

“Once-monthly infusions of 30 minutes reduced amyloid plaques on average by 84% compared to the start of the study” 

Digging Deeper Into the Data on Kisunla:

The Washington Post (July 2, 2024) parrots the Lilly message this way:

“Kisunla slowed the cognitive and functional decline in patients with mild cognitive impairment by 35 percent over 18 months, a clinical trial found. The drug works by clearing a sticky plaque in the brain called amyloid beta, which is associated with the disease.”

Most people would likely be impressed with a number like 35%. We have analyzed the actual data in detail at this post:

How Good Is Donanemab for Alzheimer’s Disease?

If you take the time to read this article, you will discover some fascinating information. I encourage you to take a few minutes to dig into the data at this link.

I know you are busy…so here is the executive summary taken from the TRAILBLASER-ALZ 2 Phase 3 study published in JAMA, Aug. 8, 2023.

The key metrics come from the integrated Alzheimer’s Disease Rating Scale (iADRS). It is a 144 point rating scale. People who score 144 points are perfect. Their brains are brilliant.

People who score 0 are in extremely bad shape. Their brains are not working well and that would be an understatement. The participants in the clinical trial averaged about 106 on the 144 point scale at the start of the study (baseline).

• After 76 weeks the iADRS score in the donanemab group declined 6.02 points
• After 76 weeks the iADRS score in the placebo group declined 9.27 points.
• The difference was 3.25 points after 76 weeks.
• This was a 144 point rating scale!

The FDA characterizes the difference as 2.92 points, which was statistically significant. But was reducing brain slippage by such a small amount over a year and a half really a breakthrough?

The authors of the JAMA study state that a:

“…meaningful within-patient change (MWPC) is a change of 5 points for those with Alzheimer disease with MCI [mild cognitive impairment] and 9 points for those with Alzheimer disease with mild dementia.”

Please draw your own conclusions.

A People’s Pharmacy Perspective on Kisunla

We do not believe that donanemab is a breakthrough against Alzheimer’s disease. It is unlikely to restore memories to people with AD. That means people with significant cognitive decline are not likely to be able to go back to work, balance their checkbook or avoid a nursing home.

You might think that our in-depth analysis of donanemab data would be highly rated by Google. And yet when you do a search for “How Good Is Donanemab for Alzheimer’s Disease?” it does not show up until page 6. In other words, it is virtually invisible to web visitors. Our number crunching is not particularly welcomed by Google’s algorithm. What comes up first if you put Kisunla into a Google search? A sponsored post of course, at kisunla.lilly.com.

The Price of Kisunla:

According to the Washington Post (July 2, 2024):

“The estimated cost for a six-month course of the therapy is $12,522. A full year of treatment is projected to cost $32,000, according to the drugmaker. However, many people probably will not pay the full list price in part since Medicare is expected to cover the treatment for certain patients.”

There will be other costs associated with Kisunla. Brain MRI scans will become necessary to detect amyloid plaque or bleeding in the brain. They will add substantially to the total cost of treatment.

Brain Shrinkage?

We have one other concern about anti-amyloid drugs. Neither the FDA nor drug companies want to talk about this reaction. It has to do with brain atrophy (shrinkage) after prolonged treatment. Here is a link to an article we have written on this topic.

Conflicting Results from Anti-Alzheimer’s Treatments: Brain Shrinkage?

A review published in the journal Neurology (May 16, 2023) analyzed data from 31 clinical trials of anti-amyloid drugs for Alzheimer’s disease.

The authors conclude:

These data reveal the potential for anti-Aβ [amyloid beta] therapies to compromise long-term brain health by materially accelerating brain atrophy and provide new insight into the adverse impact of ARIA [Amyloid-related imaging abnormalities].”

ARIA is a significant concern with all the anti-amyloid monoclonal antibody treatments (MABs). Brain swelling and bleeding (hemorrhages) show up on brain scans. Other side effects of of MABs like donanemab include “infusion-related reactions” which may appear as “flu-like symptoms, nausea, vomiting and changes in blood pressure, and hypersensitivity reactions, including anaphylaxis (severe, life-threatening allergic reaction) and angioedema (swelling).” Other adverse reactions include headache, dizziness and falls.

Final Words:

There will be much written about the latest monoclonal antibody treatment for Alzheimer’s disease. Perhaps Kisunla will eventually turn out to be an important advance against AD. It is also possible that it will be disappointing. In either case, the financial cost will be substantial. Will it break the Medicare bank? Only time will tell.

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