The FDA has approved several drugs to treat Alzheimer’s, a disease that causes cognitive decline in the elderly. A third approved drug, according to the New York Times, is Kisunla, made by Eli Lilly, which could modestly slow cognitive decline in the initial stages of the disease but also carry safety risks.
According to the FDA, Alzheimer’s disease is an irreversible, progressive brain disorder. Alzheimer’s disease affects more than 6.5 million Americans. The disease slowly destroys the memory and thinking skills of the people who have the disease – eventually resulting in the brain being unable to carry out simple tasks. Alzheimer’s is characterized by brain changes— “including amyloid beta plaques and neurofibrillary, or tau, tangles—that result in loss of neurons and their connections.”
How long is Kisunla used?
The FDA’s approval of the drug, donanemab, (to be sold through the brand name Kisunla), was shown (according to studies) to modestly slow the pace of cognitive decline in early stages of the disease. Kisunla, made by the pharmaceutical company Eli Lily, is similar to another drug, Lequembi, manufactured by Eisai and Biogen, which the FDA approved in 2023. Both drugs are intravenous infusions that “attack a protein involved in Alzheimer’s, and both can slow the unfolding of dementia by several months.”
Leqembi is given every two weeks while Kisunla is given every four weeks. Both Kisunla and Leqembi have significant safety risks.
Eli Lily states that the appeal of Kisunla (to doctors, insurers, and patients) is that patients can stop using Kisunla after the drug “clears the protein, amyloid, which clumps into plaques in the brains of people with Alzheimer’s.” An Eli Lily executive stated that “once you’ve removed the target that you’re going after, you then can stop dosing.” The ability to stop using Kisunla may help reduce the drug’s cost, inconvenience, and side effects.
According to the New York Times article, Eli Lilly stated that 17% of patients who received the drug during the 18-month-long clinical trial were able to discontinue the drug at six months, 47 % within one year, and 69% within 18 months. In addition, the cognitive decline of Kisunla users continued to slow even when patients stopped taking the drug. Eli Lilly is evaluating the long-term cognitive benefits of Kisunla.
Kisunla will list for $32,000 for a course of therapy lasting a year. “Leqembi costs $26,000 per year, but is not stopped after amyloid is cleared.”
Both Kisunla and Leqembi are considered only an incremental step in the search for effective Alzheimer’s treatments. Some experts state that the cognitive decline isn’t noticeable enough.
Alzheimer’s drugs that attack amyloid
Kisunla and Lequembi both attack amyloid, which starts to accumulate in the brain years before symptoms appear. Kisunla and Lequembi were preceded by the drug Aduhelm which was approved in 2021. Aduhelm was “discontinued last year because there was insufficient evidence that it could benefit patients.” This new class of drugs does not stop or reverse memory loss and other cognitive challenges. The drugs, at best, slow down the pace of the loss of cognitive decline.
The effectiveness of Kisunla
The are criticisms of the new anti-amyloid drugs. Dr. Michael Greicius, a neurologist at Stanford University School of Medicine, states the evidence doesn’t support their use and he isn’t prescribing Lequembi and won’t prescribe Kisunla. The doctor argues that
“If the drugs were effective, the data should show that individual patients who had more amyloid removed from their brains experienced slower rates of cognitive decline, just as medications for H.I.V. have shown that the more a drug reduces a patient’s viral load, the better that patient’s health and likelihood of survival.
Dr. Greicius asserts that the necessary data is not supported by the clinical studies.
“Dr. B. Joy Snider, a professor of neurology at Washington University School of Medicine who has been involved in trials of the drugs and previously served as a consultant to both Eisai and Lilly,” says that while slowing of the decline of cognitive function is small, the drug could still have benefits such as “delaying progression from mild forgetfulness to having to be reminded about appointments.”
She states that:
“At least at the group level, clearing of amyloid correlates with slowing of disease progression.” “It’s going to be hard to see these correlations in an individual patient,” because memory and thinking problems can fluctuate and because during testing “you don’t know if you’re getting a good day or bad day.”
The FDA approval decision states that the efficacy of Kisunla was evaluated in a double-blind, placebo-controlled, parallel-group study (Study 1, NCT04437511) in patients with Alzheimer’s disease. The patients in the study had “confirmed presence of amyloid pathology and mild cognitive impairment or mild dementia stage of disease.” The study included 1736 patients.
The FDA found that patients who took Kisunla (as compared to a placebo) showed a “statistically significant reduction in clinical decline” based on several Alzheimer scales and on one dementia scale.
The patients ranged from 59 to 86, with a mean age of 73. 57% were female, “91% were White, 6% were Asian, 4% were Hispanic or Latino, and 2% were Black or African American.”
FDA’s safety analysis of Kisunla
The boxed-warning for Kisunla states that Amyloid-related imaging abnormalities (ARIA) include:
“Temporary swelling in areas of the brain that usually resolves over time and may be accompanied by small spots of bleeding in or on the surface of the brain. ARIA usually does not have symptoms, although serious and life-threatening events rarely can occur.”
The most common side effects of Kisunla were ARIA and headache.
According to the New York Times, “about one-fourth of those on donanemab experienced swelling or bleeding in the brain. While most of the cases were mild or asymptomatic, about two percent were serious, and the side effects were linked to the deaths of three patients.”
The FDA safety analysis reviewed other concerns. The FDA decision and the New York Times story said there are many other questions about the Kisunla, anti-amyloid drugs, and cognitive decline that need to be asked and studied. Many other drugs are in clinical trials for Alzheimer’s, “including drugs attacking important features like tau tangles and neuroinflammation.
The are other concerns such as the cost of tests to determine if a patient has amyloids, the cost of the drugs, and when people should be diagnosed.
The FDA recently approved a new drug, called Kisunla, which is the third in a class of Alzheimer’s drugs. The class of drugs focuses on whether a patient has developed amyloids. The class of drugs does not reverse memory loss or cognitive decline. At best, the drug helps slow the rate of decline of Alzheimer’s disease. Doctors who treat patients with Alzheimer’s disease and dementia should understand which drugs are available, their benefits, their risks, and their effectiveness.
Avoid common FDA mistakes marketing health products
Avoid these common FDA mistakes marketing health products: communicating with FDA without legal counsel, making disease claims, misunderstanding the rules.
Doctors who prescribe medications for Alzheimer’s disease and dementia should contact Cohen Healthcare Law Group, PC to review their legal and healthcare compliance requirements. Our experienced healthcare lawyers advise medical manufacturers, medical businesses, and medical practices about compliance laws and regulations issues.
Contact our healthcare law and FDA attorneys for legal advice relevant to your healthcare venture.