Drugmaker Eli Lilly announced on Wednesday that a clinical trial of an experimental Alzheimer’s drug has shown it can slow the progression of the dreaded disease and give patients more time when they can still live independently, performing tasks like preparing meals, going to the store, and driving a car.
Lilly announced its results, from a trial involving 1,736 patients, in a press release, as required by the Securities and Exchange Commission. A peer-reviewed article will follow.
The drug, donanemab, is not a cure, but along with two other drugs recently approved by the Food and Drug Administration, it could be a turning point in the long and frustrating quest to find a cure for Alzheimer’s disease.
“These all point in the same direction,” said Dr. Ronald Petersen, director of the Alzheimer’s Disease Research Center at Mayo Clinic. He added that the results of donanemab were “modest” but “significant”.
Dr. Petersen has done paid consulting work for pharmaceutical companies, including Lilly. He was not involved in the design or execution of any of the recent trials.
Dr. Samuel Gandy, professor of Alzheimer’s disease research at Mount Sinai, was more moderate.
“Families and researchers are stuck with what we know now, which is that two drugs have statistically significant but only modest clinical benefit,” he said, echoing Dr. Petersen’s assessment. He consulted and received research support from pharmaceutical companies, but did not participate in the Lilly trial.
Dr Petersen said patients and their families should be made aware of a serious side effect of donanemab – a risk of brain swelling that can lead to death. Three patients in the Lilly trial have died.
A similar percentage of deaths from the same side effect followed in the clinical trial of Leqembi, an FDA-approved Alzheimer’s drug from the company Eisai. A third drug, Aduhelm, has also been approved by the FDA, but is rarely used due to concerns about its efficacy and high price. Brain swelling has been reported in its clinical trial and deaths have been reported in patients taking Aduhelm after its approval.
The results come after decades of failed attempts, desperation, discouragement and billions of dollars spent. Most of the big pharmaceutical companies have simply given up on Alzheimer’s drugs.
After these failures, some researchers decided that a main hypothesis about the disease – that it is caused by hard Brillo-like plaques in the brain made up of amyloid protein – was incorrect. But the successes of new drugs, which attack amyloid, reinforce the hypothesis.
Taking the meds is not like taking an antibiotic and seeing the fever go away. To measure the effectiveness of the new drug, Lilly researchers instead looked at the likelihood of patients progressing through the Alzheimer’s disease categories from mild cognitive impairment to mild dementia, or mild dementia to moderate. These are significant changes that have a profound effect on patients and their families.
The company reported that two to three out of 10 patients taking donanemab progressed over the next 18 months compared to the expected three to four patients who did so while taking a placebo.
They also studied the likelihood of a patient’s disease remaining absolutely stable over a period of time.
“One of the common things we always hear from Alzheimer’s patients who are very early in the disease is, ‘If I could just stay at this level, I could get through this’ “, said Dr. Daniel Skovronsky, medical and scientific director. at Eli Lilly and Company.
With the new drug, 47% of patients remained stable over the following year, compared with 29% who took the placebo.
In the Lilly trial, 24% of patients had the side effect of brain swelling and bleeding, and 6% had symptoms such as dizziness, headache or fainting. This is double the rate seen with Leqembi, the Eisai drug.
But, Dr. Skovronsky said, it’s difficult to compare data across trials because the studies had different patient populations — Leqembi’s patients had less severe Alzheimer’s disease — and different designs. MRI scans were performed on different schedules and the way the scans are read may vary.
Deaths from brain swelling and bleeding are rare, but these drugs “are not right for everyone,” Dr. Petersen said.
“They don’t make you better but they slow down the disease,” he said.
Dr Petersen added that what is really needed is a drug that stops the disease before symptoms appear.
With that goal in mind, Eisai and Lilly are testing their drugs in new studies on people who have high amounts of amyloid in their brains but who don’t yet show symptoms of Alzheimer’s disease.
Advocacy groups applauded the data from the Lilly trial.
George Vradenburg, president and co-founder of UsAgainstAlzheimer’s called the donanemab results “exciting news.” Lilly, along with other companies, gives the group general funding, but not for a specific project.
In a press release, he said: “Talk to anyone with early-stage Alzheimer’s disease and they will tell you that living independently and having a better quality of life for a longer period of time are among the most important things to her.”