The Food and Drug Administration on Tuesday approved a new Alzheimer’s treatment called donanemab, paving the way for the third addition to a new class of drugs aimed at slowing brain decline in patients facing the early stages of the disease.
Dubbed Kisunla by drugmaker Eli Lilly, the approval of donanemab follows years of hurdles and delays in bringing the experimental Alzheimer’s treatment to market, despite promising clinical trial results.
Eli Lilly says the drug will be available within weeks of approval.
“Kisunla showed very significant results for people with early symptomatic Alzheimer’s disease, who urgently need effective treatment options. We know that these drugs have the greatest potential benefit when people are treated earlier in their disease, and we are we work hard in partnership with others to improve detection and diagnosis,” said Anne White, president of Eli Lilly’s neuroscience arm, in a press release.
The FDA previously rejected Eli Lilly’s request for accelerated approval last year, citing concerns about its long-term safety record. After Eli Lilly submitted more data to the FDA, the company said it expected the agency to decide on approval by the end of March.
That decision was delayed after the FDA appointed an advisory committee to deal with questions about the drug’s safety and how effectiveness was measured in its trials. The panel ultimately voted unanimously last month in favor of the drug’s benefits outweighing its risks for patients in the early stages of Alzheimer’s disease.
How does donanemab work?
Donanemab is part of a class of Alzheimer’s treatments called anti-amyloid monoclonal antibodies, which work to fight the buildup of a protein in the brain called amyloid plaque that has been linked to Alzheimer’s disease.
The antibody in donanemab targets amyloid plaques that have built up in patients by binding to and removing them from the brain.
Patients in Eli Lilly’s trials were given intravenous infusions of donanemab over about half an hour, every four weeks. Depending on brain scans that measure levels of amyloid in the brain, patients were able to stop taking the drug after six months.
IN her evidence, the company says that almost half of the patients were able to significantly clear amyloid after about a year of taking the drug. Patients saw no “relapse of amyloid plaque” in the year after treatment ended.
Eli Lilly
The only other Alzheimer’s treatment that works similarly on the market is lecanemab, named as Leqembi by drugmakers Eisai and Biogen. An earlier drug called aducanumab (marketed as Aduhelm) from Biogen was discontinued in January.
Beyond effectiveness, Eli Lilly has also touted a number of other reasons patients may choose their drug over lecanemab.
Donanemab infusions are shorter and less frequent. Trial participants were also able to stop using the drug after the amyloid plaque was removed, “which may result in lower treatment costs and fewer infusions,” a company spokesman said.
How much will the treatment cost?
Eli Lilly says it will start with a list price that adds up to $32,000 for 12 months of treatment, though the actual cost will depend on how long patients take the drug. Some patients in the clinical trials were able to stop treatment after six months, based on results from brain scans, while others took it for 18 months.
Last year, Eisai defended its list price of $26,500 a year when it launched Leqembi sales.
But most patients also don’t pay full list price for prescription drugs. For Medicare Part B patients, the Centers for Medicare and Medicaid Services said donanemab will be covered the same way it covers lecanemab (Leqembi), with patients paying a co-insurance of 20%. after completing their deduction. These patients will have to receive the drug from doctors enrolled in a study that collects data on its effectiveness.
“CMS is committed to helping people get timely access to treatments and improving care for people with Alzheimer’s disease and their families,” a CMS spokesperson said.
Eli Lilly noted in a statement: “The potential to complete treatment after a course of limited-duration therapy, along with once-monthly 30-minute infusions, may result in lower patient out-of-pocket treatment costs and fewer infusions compared to other amyloid-targeting therapies.”
How effective was the treatment for Alzheimer’s symptoms?
Eli Lilly measured the effectiveness of donanemab primarily through rating scales designed to measure cognitive and functional decline caused by dementia symptoms in patients with early stages of Alzheimer’s.
Compared to patients who received only a placebo, Eli Lilly said those who received the drug saw their decline slow by as much as 22% at 76 weeks after starting donanemab infusions.
“Importantly, the magnitude of the impact on these clinical endpoints meets and in some respects exceeds previous approvals for demonstrating clinical benefit and effectiveness,” the company said of the results in an information document provided to the FDA panel.
The company says this translated into effectively extending how long it took for patients to progress to the next stage of Alzheimer’s disease.
What are the side effects of donanemab?
Labels for all FDA-cleared anti-amyloid treatments to date for Alzheimer’s already carry a boxed warning about “amyloid-related imaging abnormalities” that can show up on MRI scans.
While these abnormalities generally do not result in any symptoms, they have been linked to rare but serious issues in some patients, such as brain function problems and seizures.
These abnormalities were seen in about a quarter of participants in Eli Lilly’s trials of donanemab. At least five deaths were reported in donanemab recipients in patients with these types of abnormalities, mostly from brain hemorrhages.
Eli Lilly says its trials of donanemab tested the drug more difficult for patients to treat than other treatments studied at the same time. That means the trial included older trial participants as well as those with a gene called APOE ε4 that can increase the risk of Alzheimer’s, as well as these abnormalities.
About 1 in 10 trial participants who received donanemab also experienced an infusion reaction, compared with 0.5% of placebo participants. The most common symptoms included chills, skin rash, nausea, shortness of breath, headache and chest pain.
Approximately 3% of participants treated with donanemab developed hypersensitivity to the infusion, including 0.3% who had a severe allergic reaction.