The drug manufacturer Eli Lilly announced on Wednesday that a clinical trial of an experimental Alzheimer’s drug showed it can slow progress of the feared disease and allow patients to have more time when they can still live independently, performing tasks like cooking meals, going to the store and driving a car.
Lilly announced its results, from a trial involving 1,736 patients, in a news release, as required by the Securities and Exchange Commission. A peer-reviewed paper will follow.
The drug, donanemab, is not a cure, but along with two other drugs recently approved by the Food and Drug Administration, it may be a turning point in the long and frustrating quest to find an Alzheimer’s treatment.
“These all point in the same direction,” said Dr. Ronald Petersen, the director of the Alzheimer’s Disease Research Center at the Mayo Clinic. He added that the donanemab results were “modest” but “meaningful.”
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, a professor of Alzheimer’s disease research at Mount Sinai, was more subdued.
“Families and researchers are stuck with what we know now, which is that two drugs have a statistically meaningful but only modest clinical benefit,” he said, echoing Dr. Petersen’s assessment. He has consulted and received research support from pharmaceutical companies but was not involved in the Lilly trial.
Dr. Petersen said that patients and their families must be counseled about a dire side effect of donanemab — a risk of brain swelling that can result in death. Three patients in the Lilly trial died.
A similar percentage of deaths from the same side effect followed in the clinical trial of Leqembi, an F.D.A.-approved Alzheimer’s drug from the company Eisai. A third drug, Aduhelm, was also approved by the F.D.A., but is rarely used because of concerns about its effectiveness and its high price. Brain swelling was reported in its clinical trial and deaths were reported in patients taking Aduhelm after it was approved.
The results come after decades of failed attempts, despair, discouragement and billions of dollars spent. Most big pharmaceutical companies simply gave up on Alzheimer’s drugs.
After those failures, some researchers decided that a leading hypothesis about the disease — that it is driven by hard, Brillo-like plaques in the brain made of amyloid protein — was incorrect. But the successes of the new drugs, which attack amyloid, bolster the hypothesis.
Taking the drugs is not like taking an antibiotic and seeing a fever go away. To measure the new drug’s effectiveness, the Lilly researchers instead looked at how likely patients were to progress through the categories of Alzheimer’s disease, going from mild cognitive impairment to mild dementia, or from mild to moderate dementia. 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 as compared to the expected three to four patients who did while taking a placebo.
They also studied how likely it was that a patient’s disease would remain absolutely stable over a period of time.
“One of the common things we always hear from patients who have Alzheimer’s but are very early in the disease is, ‘If I could just stay at this level I could get by,’” said Dr. Daniel Skovronsky, chief medical and scientific officer at Eli Lilly and Company.
With the new drug, 47 percent of patients stayed stable over the subsequent year compared with 29 percent who took the placebo.
In the Lilly trial, 24 percent of patients had the side effect of brain swelling and bleeding, and 6 percent had symptoms like dizziness, headache or fainting. That is twice the rate observed with Leqembi, the Eisai drug.
But, Dr. Skovronsky said, it is difficult to compare data across trials because the studies had different patient populations — the Leqembi patients had less severe Alzheimer’s — and different designs. The M.R.I. scans were done on different schedules, and the way the scans are read can vary.
Deaths from brain swelling and bleeding are rare, but still these drugs “are not for everyone,” Dr. Petersen said.
“They do not make you better but they slow the disease,” he said.
Dr. Petersen added that what is really needed is a drug that stops the disease before symptoms arise.
With that goal in mind, Eisai and Lilly are testing their drugs in new studies of people who have large amounts of amyloid in their brains but no symptoms yet of Alzheimer’s.
Advocacy groups applauded the data in the Lilly trial.
George Vradenburg, chairman 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 any specific project.
In a news release, he said, “Talk to anyone with early-stage Alzheimer’s and they will tell you that living independently and having a higher quality of life for a longer period of time are among the most important things to them.”
Source: New York Times
