FDA approves new Alzheimer's treatment, donanemab from Eli Lilly
The Food and Drug Administration approved a new Alzheimer's treatment called donanemab on Tuesday, clearing the way for the third addition to a new class of drugs aimed at slowing the brain's decline in patients facing the early stages of the disease.
Branded as Kisunla by drugmaker Eli Lilly, donanemab's approval follows years of setbacks and delays in getting the experimental Alzheimer's treatment to market, despite promising clinical trial results.
Eli Lilly says the drug will be available within weeks following the approval.
"Kisunla demonstrated very meaningful results for people with early symptomatic Alzheimer's disease, who urgently need effective treatment options. We know these medicines have the greatest potential benefit when people are treated earlier in their disease, and we are working hard in partnership with others to improve detection and diagnosis," Anne White, president of Eli Lilly's neuroscience arm, said in a news release.
The FDA previously rebuffed Eli Lilly's request for accelerated approval last year, citing concerns about its long-term safety data. After Eli Lilly submitted more data to the FDA, the company said it expected the agency would decide on approval by the end of March.
That decision was delayed after the FDA scheduled an advisory committee to wrestle with questions over the drug's safety issues 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 combat 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 donanemab infusions for around half an hour, every four weeks. Depending on brain scans measuring amyloid levels in the brain, patients were able to stop taking the drug after as early as six months.
In its trials, the company says almost half of patients were able to meaningfully clear out amyloid after around a year after taking the drug. Patients saw no "rebound of amyloid plaque" in the year after treatment wrapped up.
The only other Alzheimer's treatment that works in a similar way on the market is lecanemab, branded 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 handful of other reasons that patients might choose their drug instead of lecanemab.
Donanemab infusions are shorter and less frequent. Trial participants were also able to stop using the drug after amyloid plaque was removed, "which can result in lower treatment costs and fewer infusions," a company spokesperson said.
How much will the treatment cost?
Eli Lilly says it will launch 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 the 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 per year when it launched sales of Leqembi.
But most patients also do not pay the full list price for prescription drugs. For patients with Medicare Part B, the Centers for Medicare and Medicaid Services said donanemab will be covered in the same way it covers lecanemab (Leqembi), with patients paying a 20% coinsurance after they meet their deductible. These patients will need to get the drug from doctors enrolled in a study gathering data tracking 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 limited-duration course of therapy, along with 30-minute infusions once per month, could 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 donanemab's effectiveness primarily through rating scales designed to measure the cognitive and functional decline caused by dementia symptoms in patients with early stages of Alzhiemer's.
Compared with patients who received only a placebo, Eli Lilly said those who got the drug saw their decline slow by up to 22% at 76 weeks after first starting the donanemab infusions.
"Importantly, the magnitude of impact on these clinical endpoints meets, and in several respects exceeds prior approvals for demonstration of clinical benefit and effectiveness," the company said of the results in a briefing document given to the FDA panel.
The company says this translated to effectively prolonging how long it took until patients stepped down into the next stage of Alzheimer's disease.
What are the side effects of donanemab?
The labels for all of the anti-amyloid treatments greenlighted by the FDA 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 result in no symptoms, they have been linked to rare but serious issues in some patients like brain function issues and seizures.
These abnormalities were seen in around a quarter of participants in Eli Lilly's trials of donanemab. At least five deaths were reported in donanemab recipients in patients with these kinds of abnormalities, mostly from hemorrhages in the brain.
Eli Lilly says their trials of donanemab tested the drug in harder to treat patients than other treatments studied around 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.
Close to 1 in 10 trial participants who took donanemab also experienced a reaction to the infusion, compared to 0.5% of placebo participants. The most common symptoms included chills, skin reddening, nausea, shortness of breath, headache and chest pain.
Approximately 3% of donanemab-treated participants developed hypersensitivity to the infusion, including 0.3% who had a severe allergic reaction.