The Food and Drug Administration (FDA) 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.
Called Kisunla by drugmaker Eli Lilly, the approval of donanemab follows years of setbacks and delays in getting the experimental Alzheimer’s treatment to market, despite Promising results from clinical trials.
Eli Lilly says the drug will be available within weeks of approval.
“Kisunla has demonstrated highly 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,” said Anne White, president of Eli Lilly’s neuroscience business, in a press release.
Last year, the FDA had already rejected Eli Lilly’s request for accelerated approval, citing concerns about its long-term safety data. After submitting more data to the FDA, Eli Lilly said it expected the agency to decide whether to approve its drug by the end of March.
That decision was delayed after the FDA asked an advisory committee to review questions about the drug’s safety and how effectiveness was measured in trials. The committee ultimately voted unanimously last month that the drug’s benefits outweigh its risks for patients with early-stage Alzheimer’s disease.
How does donanemab work?
Donanemab is in a class of Alzheimer’s disease 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 the brain and clearing them.
Patients in Eli Lilly’s clinical trials received intravenous infusions of donanemab over about a half-hour, every four weeks. Depending on the results of brain scans measuring amyloid levels in the brain, patients were able to stop taking the drug after just six months.
In his trialsAccording to the company, nearly half of patients were able to significantly clear amyloid about a year after taking the drug. Patients did not see “amyloid plaque rebound” in the year after treatment ended.
Eli Lily
The only other Alzheimer’s treatment on the market that works similarly is lecanemab, marketed as Leqembi by drugmakers Eisai and Biogen. An earlier drug called aducanumab (marketed under the name Aduhelm) from Biogen was discontinued in January.
Beyond efficacy, Eli Lilly also discussed a handful of other reasons why patients might choose its drug over lecanemab.
Donanemab infusions are shorter and less frequent. Trial participants were also able to stop using the drug after amyloid plaques cleared, “which may result in reduced treatment costs and fewer infusions,” a company spokesperson said.
How much will the treatment cost?
Eli Lilly said the drug’s introductory price would be $32,000 for 12 months of treatment, but the actual cost will depend on how long patients take the drug. Some patients in clinical trials were able to stop taking it after six months, based on brain scan results, 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 don’t 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 the same way as lecanemab (Leqembi), with patients paying 20% coinsurance once they have reached their deductible. These patients will need to obtain the drug from doctors participating in a study collecting 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 said in a statement: “The ability to complete treatment after a limited duration of therapy, as well as 30-minute infusions once a month, could result in lower out-of-pocket treatment costs and fewer infusions compared to other amyloid-targeted therapies.”
How effective was the treatment for Alzheimer’s symptoms?
Eli Lilly measured donanemab’s effectiveness primarily using assessment scales designed to measure cognitive and functional decline caused by dementia symptoms in patients with early-stage Alzheimer’s disease.
Compared with patients who received only a placebo, Eli Lilly said those who received the drug saw their decline slow by up to 22% at 76 weeks after starting donanemab infusions.
“Importantly, the magnitude of the impact on these clinical endpoints is consistent with, and in many respects exceeds, prior approvals for demonstration of clinical benefit and efficacy,” the company said of the findings in a briefing document provided to the FDA panel.
The company says this has the effect of extending the time it takes for patients to progress to the next stage of Alzheimer’s disease.
What are the side effects of donanemab?
The labels of all anti-amyloid treatments approved to date by the FDA for Alzheimer’s disease already include a boxed warning about “amyloid-related imaging abnormalities” that can appear on MRI scans.
Although these abnormalities usually do not cause any symptoms, they have been associated with rare but serious problems in some patients, such as brain function problems and seizures.
These abnormalities were seen in about a quarter of participants in Eli Lilly’s clinical trials of donanemab. At least five deaths have been reported in patients receiving donanemab who had these abnormalities, mostly due to brain hemorrhages.
Eli Lilly says its trials of donanemab tested the drug in patients who were harder to treat than other treatments studied at the same time. That means the trial included older participants as well as people who carry a gene called APOE ε4 that can increase the risk of Alzheimer’s disease as well as those abnormalities.
Nearly one in ten participants taking donanemab also had an infusion reaction, compared with 0.5% of participants taking placebo. The most common symptoms were chills, skin flushing, 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.