July 2, 2024: FDA approves a new medication for Alzheimer’s disease
On July 2, the U.S. Food and Drug Administration (FDA) approved donanemab which has been developed by Eli Lilly and will be marketed under the name Kisunla™ for the treatment of people living with early symptomatic Alzheimer’s disease, which includes mild cognitive impairment and the mild dementia stage of Alzheimer’s disease, with confirmed amyloid plaques. Amyloid is a protein produced naturally in the body that can clump together to create amyloid plaques characteristic of Alzheimer’s disease. The excessive buildup of amyloid plaques in the brain may lead to memory and thinking issues associated with Alzheimer’s disease.
Donanemab is amyloid plaque-targeting therapy with evidence to support stopping therapy when amyloid plaques are sufficiently lowered and will be available as a once-monthly intravenous (IV) infusion. A late-stage clinical trial with this new compound showed meaningful results for patients who took donanemab, with about 35% lower risk of progression of the disease over a year and a half versus in patients who received a placebo. This amounted to a 4.5 – 7.5 months delay in progression on the clinical scales used to measure decline by the end of the study. Donanemab reduced amyloid plaques on average by 61% at 6 months, 80% at 12 months, and 84% at 18 months compared to the start of the study.
While rare, there were some serious adverse events during the clinical drug trial. Individuals on donanemab in the clinical trial had a slightly higher mortality rate of 1.9%, compared with 1.1% among individuals treated with placebo. Donanemab has been associated with amyloid-related imaging abnormalities (ARIA), a potential side effect with amyloid plaque-targeting therapies. While ARIA can be identified early with a magnetic resonance imaging (MRI) scan and is generally managed by stopping medication, ARIA can potentially cause serious and life-threatening health complications. For this reason, regular MRI monitoring before and during treatment with donanemab is required.
There are now multiple medications that have been FDA-approved for the treatment of individuals with early Alzheimer’s disease. Individuals who are interested in exploring their potential eligibility for donanemab or other treatments that are currently available for Alzheimer’s disease should consult with their healthcare provider.
The Cleveland Alzheimer’s Disease Research Center (CADRC) team is pleased to see ongoing development of therapeutics for this devastating condition. To learn more about the work of the CADRC please reach out via email: contact@clevelandadrc.org or call 1-833-311-2372
January 2023
U.S. FDA Approves Second Anti-Amyloid Medication for Treatment of Alzheimer’s Disease (AD)
On January 6, 2023, the US Food and Drug Administration (FDA) approved the anti-amyloid beta protofibril antibody lecanemab for the treatment of patients with Alzheimer’s disease (AD). Lecanemab will be marketed under the name Leqembi by the pharmaceutical company Eisai. Similar to another related AD drug, aducanumab (marketed as Aduhelm by the pharmaceutical company Biogen), lecanemab was approved using the FDA’s accelerated approval pathway, which fast-tracks new medications that have potential to provide a meaningful therapeutic benefit over existing treatment for a serious or life-threatening illness.
The FDA notes Leqembi an amyloid beta-directed antibody indicated for the treatment of Alzheimer’s disease. Treatment with LEQEMBI should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was initiated in clinical trials. There are no safety or effectiveness data on initiating treatment at earlier or later stages of the disease than were studied. The FDA has approved lecanemab based upon results of the CLARITY AD clinical trial, which showed modest slowing of decline for patients with mild AD.
The clinical trial enrolled nearly 1,800 patients with mild cognitive impairment or mild dementia due to AD in whom amyloid pathology in the brain was confirmed. Clinical trial treatment was either lecanemab or placebo. After 18 months of treatment, lecanemab appeared to slow cognitive decline by 27% compared with placebo.
While having another FDA-approved treatment for AD is very exciting and has potential to change the trajectory of decline for people with early-stage AD dementia, any potential benefits for patients with mild AD need to be balanced with consideration for an increased risk of drug-related complications. In the lecanemab clinical trials, the amyloid-related complications of edema (brain swelling) or microhemorrhages (mini-bleeds in the brain) occurred in about 1 in 5 patients taking lecanemab. This suggests a need for close monitoring for drug-related complications in patients who receive treatment with lecanemab.
It is important to note that clinical situations differ across individuals and patients may have different responses or contra-indications to any medication. Individuals who are interested in exploring whether lecanemab or another medication treatment is appropriate for them are encouraged to speak with their clinicians.
June 2021
On Monday, June 7, 2021, the Food and Drug Administration (FDA) approved aducanumab to treat Alzheimer’s disease under the “Accelerated Approval Program”. This program is designed for earlier approval of treatments for serious conditions without current effective therapies. There was evidence that aducanumab reduced amyloid plaques in the brain, a hallmark of Alzheimer’s disease. The approval comes with a condition that further follow-up studies are required to confirm the benefit on symptoms and day-to-day functioning. Aducanumab is not a cure for Alzheimer’s disease, and it remains unclear whether it helps treat the symptoms of Alzheimer’s disease.
Alzheimer’s disease is the most common cause of dementia, affecting about 6 million Americans and about 30 million people around the world. Aducanumab targets amyloid plaques in the brain that are believed to be an essential component of Alzheimer’s disease. This is the first treatment for Alzheimer’s disease that targets amyloid plaques.
With no drugs on the market to treat amyloid plaques associated with Alzheimer’s disease, the FDA’s decision came after months of study and debate by experts in the field. As scientists and patient advocate communities have examined the issue, one question was whether the drug slowed Alzheimer’s disease progression enough to offer patients benefits, compared with the risk of side effects. This will be a component of the long-term follow up of patients receiving the medication.
In clinical trials, aducanumab, a medication that is given intravenously (IV) on an every 4 week basis, was tested with people in early stage of Alzheimer’s disease who were showing symptoms, such as memory loss, and who tested positive for amyloid plaques in the brain. We await critical information regarding additional recommendations for the clinical use of aducanumab (Aduhelm). It may take several months for use and access processes from pharmacies and payers/insurers to be determined and for aducanumab to be available to patients.
What types of individuals should or should not receive aducanumab?
Aducanumab should only be initiated in patients with mild cognitive impairment or mild dementia stages of the disease, the population in which the treatment was initiated in clinical trials. As with any medical treatment, appropriateness depends on a variety of factors. Aducanumab is not for use in any dementia other than Alzheimer’s disease. Aducanumab is for people with Alzheimer’s disease and will require a prescription and close clinical monitoring by clinicians who are experts in the care of individuals with Alzheimer’s disease. More specific questions about whether a specific individual should or should not receive this treatment need to be addressed with a treating clinician with expertise in Alzheimer’s disease.
Is aducanumab safe?
Like any medication, aducanumab also has side effects. The side effect seen most commonly during the studies was Amyloid-Related Imaging Abnormalities (ARIA): removing of amyloid may cause leakiness of blood vessels and swelling in the brain. Regular brain MRI scans are required during treatment with aducanumab to monitor any changes
How and when can I find out if aducanumab is right for me?
This medication is being administered via intravenous infusion, which is a more intensive and complex process than for any previous Alzheimer’s treatment. Treating clinicians may also require evaluations for the presence of amyloid protein and test for the severity of the symptoms. Managing these unprecedented complexities will delay availability for clinical use, but it is likely to be available in 2021 for some patients.
Patients and their families are encouraged to talk to their health care providers about whether aducanumab is an appropriate treatment option given their own circumstances and clinical symptoms.