New medications show promising results in Alzheimer’s treatment
A new treatment aimed at curbing the debilitating effects of Alzheimer’s disease won approval from the U.S. Food and Drug Administration (FDA) earlier this year. Lecanemab is now the second-ever treatment for the disease to receive approval. The drug will be sold under the brand name Leqembi, and clinical trials showed it is the first treatment of its kind to slow cognitive decline.
The drug is a monoclonal antibody administered to patients intravenously where it then travels to the brain to work on clearing amyloid plaques associated with Alzheimer’s and thought to be the root of its associated dementia and memory loss.
Lecanemab is the product of Massachusetts-based bio-pharmaceutical company Biogen along with Eisai in Tokyo, Japan. Clinical trials show that when taken in early stages of Alzheimer’s disease, it can slow its progression and allow patients to have more independent, productive daily life for a longer period of time.
The FDA authorized lecanemab under its accelerated approval pathway, which is only used for therapies for diseases that have few or no other treatments. That pathway does not require data from phase 3 trials, but researchers conducting those trials now say data found the drug slowed cognitive decline in about 27% of the 1,800 participants over 18 months of treatment. Biogen and Eisai asked for approval using phase 2 data instead which found lecanemab decreased brain plaques in 856 participants but did not assess whether that affected cognitive abilities.
The FDA approval means there are now two drugs available to treat Alzheimer’s, with the first one, aducanumab, getting the fast-track approval as well. A third Alzheimer’s drug, donanemab, was refused FDA accelerated pathway approval in late January due to the limited number of patients in clinical studies who had received at least 12 months of exposure to the drug.
Alzheimer’s affects more than six million adults in the United States, and it’s still unclear how well the new therapies will aid in treating them. The U.S. Centers for Medicare and Medicaid Services (CMS) has so far declined to cover aducanumab under federal insurance plans unless a patient is enrolled in a clinical trial. That would leave the patient responsible for paying the $28,000 cost for a year’s treatment on the drug.
There are lingering questions over efficacy and safety with some of the therapies.
“Lecanemab is similar to the previously approved aducanumab, which has generated a lot of controversies, and the approval for lecanemab is under the shadow of its predecessor,” explains Dr. Cheuk Mun Au, Geriatric Fellow with Washington Health System (WHS). “Although aducanumab had generated some controversies, the original research for lecanemab has so far generated promising results. As the last medication approved for treatment of Alzheimer’s disease was in 2003, approval for lecanemab certainly brings more hope to the patients and their family who are suffering from this incurable condition. We believe this is a positive step in advancement of treatment.”
Some of the safety concerns are related to brain swelling or bleeding, and patients are advised to have multiple MRI brain scans while taking lecanemab.
“The cost of lecanemab for one year of treatment is more than $25,000,” says Au. “Still, we are cautiously optimistic about the medication despite its safety issues and cost barrier.”
The infusions work by releasing antibodies to target a protein linked to causing Alzheimer’s disease.
“Alzheimer’s is long thought to be a result of deposition and accumulation of a protein called amyloid protein in the brain,” says Au. “Amyloid protein forms plaque and damages the brain cells and nerve tissues, resulting in memory loss. Lecanemab has been shown to help clear these amyloid plaques in the brain and neurons, which, in turn, helps to preserve brain function and delay the onset of or prevent further cognitive decline.” Imaging studies have shown definitive evidence of reduce amounts of the plaques, but the question still remains whether that provided a benefit in preserving cognitive function.
Both aducanumab and lecanemab are monoclonal antibodies, but their exact mechanism of action is slightly different. “Clinical trials showed that lecanemab is more efficient, compared to aducanumab, in mopping up amyloid plaques,” says Dr. Ishwar Bhattarai, Attending Physician in Geriatric Medicine with Washington Health System. “However, lecanemab only showed modest clinical effects. Aducanumab, on the other hand, showed reduced amyloid plaque burden in imaging studies at the end of their study trial, but this didn’t translate much into clinical outcomes.”
He also cautioned that both drugs come with potential safety concerns. “They both can cause brain bleeds and swelling. The rate of these adverse effects is fairly consistent between the two drugs at about 25%.”
Bhattarai says the phase 3 trials for the third potential Alzheimer’s drug, donanemab, will be worth watching since some findings have shown it removes four times more amyloid plaque than aducanumab in the first six months of treatment.
All of these newly developed therapies are giving physicians reason to offer hope for the future treatment of Alzheimer’s disease.
“These new medications and multiple trials have shown promising initial results for treatment,” says Bhattarai. “We will know more about these medications as further evidence emerges in a larger patient population. It will certainly be a big advancement in treatment for Alzheimer’s disease if these trials continue to show promising results.”