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The FDA has approved the use of the drug donanemab for early Alzheimer’s treatment. Sarah Silbiger/Getty Images
  • A panel of independent advisors to the FDA previously endorsed the experimental drug donanemab (Kisunla) for the treatment of Alzheimer’s, saying the benefits outweigh the risks.
  • Eli Lilly & Company, the maker of anti-amyloid Alzheimer’s treatments, was expecting donanemab to be approved by the FDA earlier this year, but an FDA panel was convened to evaluate the safety and efficacy of donanemab.
  • As of July 2, the FDA has approved donanemab for adults with early symptomatic Alzheimer’s disease, mild cognitive impairment, and mild dementia.
  • Expert reactions to the treatment’s approval have been mixed so far.

The Food and Drug Administration (FDA) on Tuesday, July 2 approved the use of donanemab (Kisunla), the Alzheimer’s drug that had its approval blocked last year.

The drug, administered as a once-monthly injection for intravenous (IV) infusion, will become a treatment option for adults with early symptomatic Alzheimer’s disease, including people with mild cognitive impairment (MCI) and mild dementia with confirmed amyloid plaques.

Commenting on the news, Joanne Pike, DrPH, Alzheimer’s Association president and CEO said:

“This is real progress. Today’s approval allows people more options and greater opportunity to have more time. Having multiple treatment options is the kind of advancement we’ve all been waiting for — all of us who have been touched, even blindsided, by this difficult and devastating disease.”

The news comes a few weeks after a panel of external advisors to the FDA endorsed the approval of the drug on June 10 and ultimately decided that the drug’s benefits outweighed the risks that have been documented, which can include swelling and bleeding in the brain.

In a trial last year, donanemab showed “significantly slowed clinical progression” in early Alzheimer’s patients but also produced brain swelling and other adverse effects.

So, what does this decision mean for Alzheimer’s patients? Here’s what experts think.

Donanemab is one of three monoclonal antibody treatments for Alzheimer’s that includes aducanumab (Aduhelm) and lecanemab (Leqembi). All three drugs work by clearing the amyloid plaques that are characteristic of Alzheimer’s, but there was scarce evidence in early trials that clearing the plaques slowed cognitive decline.

Dementia affects more than 55 million people worldwide, and up to 70% of those people have Alzheimer’s disease, characterized by the buildup of two proteins, amyloid and tau.

Both aducanumab and lecanemab were given accelerated approval by the U.S. Food and Drug Administration (FDA) following promising trial results.

Howard Fillit, MD, co-founder and chief science officer of the Alzheimer’s Drug Discovery Foundation (ADDF), told Medical News Today that while an FDA advisory committee is not unusual for a new drug, what was unique about the case of donanemab was that since the results on efficacy and safety were so similar to Leqembi, it wasn’t expected that a committee would be established.

“I think, as they got into the due diligence on the drug, they realized there were a few things about it that they wanted to have an advisory committee on: basically three things,” Fillit said.

“There was some added benefit on efficacy, but some increase in the safety signal. There was a very unique, limited dosing schedule regimen that donanemab had, which has a lot of implications for clinical care. And there was the tau imaging, which was used for entry into the trial, but they wanted to know whether or not the tau imaging would be on the label and be required for clinical use in the real world,” he explained.

Meanwhile, Clifford Segil, DO, a neurologist at Providence Saint John’s Health Center in Santa Monica, CA, told Medical News Today that he will not suggest donanemab for his patients, citing the experimental drug’s risks.

“I believe patients with cerebral edema and brain bleeds will develop vascular dementia in the long run,” Segil said.

“Pharmaceutical companies are having issues convincing neurologists to adapt these medications into our practice that they are shifting to direct-to consumer-marketing with a goal of trying to get more patients to try these medications,” Segil continued.

“It breaks my heart to tell my patients there is an FDA approved medication for memory loss whose risks I believe outweigh its benefits. As these medications’ use does increase, and no noticeable cognitive improvement is noted, it will be removed from the marketplace similar to the first anti-amyloid medication which has already been voluntarily withdrawn. I remain extremely concerned these medications will cause patient deaths and await post-marketing surveillance to keep tabs on the adverse effects from this family of medications,” he explained.

“There is no data [that] it makes patients with Alzheimer’s dementia have any significant improvement in their cognitive complaints,” he added.

Currently available treatments for Alzheimer’s can help manage symptoms but not change the course of the disease. In an international phase 3 trial, compared to placebo, donanemab slowed cognitive decline by 35% in people with low/medium levels of tau.

In a combined population that included people with low/medium levels of tau as well as people with high levels of tau, donanemab slowed cognitive decline by about 22%.

The risks of amyloid-related imaging abnormalities (ARIAs) can produce brain swelling or bleeding. There were also some concerns with the population of the study, in which more than 91% of the participants were white.

Fillit said expectations were in line with the FDA to ultimately approve donanemab, citing the trial data and the safety measures in place to monitor the risks of ARIA.

“[I]t’s important to look at this milestone in the larger treatment landscape for Alzheimer’s, which will entail a combination therapy and precision medicine approach,” Fillit said in a statement on June 10.

“[D]onanemab will expand the first class of disease-modifying drugs, serving as the building blocks for future generations of drugs. Anti-amyloids are not a silver bullet, but they offer opportunities for patients to modify the course of the disease while the field works toward developing more novel therapies that target the underlying biology.”
— Dr. Howard Fillit

“All drugs have a risk,” Fillit said, citing the Swiss 16th-century chemist Paracelsus quote about the only difference between a drug and a poison being a dose.

“First of all, on entry into the trial, we don’t want people on anticoagulants because of the possibility of these ARIA edema and hemorrhage findings on MRI that can occur. And we want to know that person’s APO lipoprotein E genotype because people that are carrying the APOE ε4 gene are at more risk for developing some of the ARIA side effects as well,” he continued.

“So in getting into the trial, we have a bleeding disorder or anticoagulants would probably not be recommended for the drug. And people that are certainly homozygote e4 would require careful monitoring if they went on the drug,” he added.

Fillit said that careful monitoring would be required in the early stages of treatment, with MRIs in the first three to five months while potentially looking for ARIA or other signs that the drug should be halted.

“If they do occur, basically, the drug is withheld for a period of time and then reinstituted on the transfusion and stopped for a period of time,” Fillit said.

“But in the APOE ε4 people, if they’re homozygote and they have two APOE ε4’s and they develop bleeding or hemorrhage in the brain, the ARIA side effects or edema, then they may just be stopped and not put back on, depending on the severity of those findings on MRI.”

However, Segil said he believes the risks are too high for him to recommend donanemab or similar drugs.

“As a clinical neurologist who treats and diagnoses patients with dementia, I do not believe drugs like donanemab are effective treatments for patients with Alzheimer’s dementia,” Segil said.