The Alzheimer’s treatment donanemab, which is made by Eli Lilly, significantly slowed progression of the mind-robbing disease, according to clinical trial data released Wednesday by the company.
Patients who received the monthly antibody infusion during an 18-month study demonstrated a 35% slower decline in memory, thinking and their ability to perform daily activities compared with those who did not receive the treatment, Eli Lilly’s data showed.
Patients who took donanemab were 39% less likely to progress to the next stage of the disease during the study, according to the trial results.
But the treatment’s benefits will have to be weighed against the risk of brain swelling and bleeding that can be serious and even fatal in rare cases. Three participants in the trial died from these side effects.
Eli Lilly’s stock was up more than 6% in premarket trading Wednesday.
Lilly plans to apply for Food and Drug Administration approval of donanemab as soon as this quarter, according to the company. The trial studied individuals in the early stages of Alzheimer’s who had a confirmed presence of brain plaque associated with the disease.
Dr. Daniel Skovronsky, Lilly’s chief scientific and medical officer, said donanemab demonstrated the highest level of efficacy of any Alzheimer’s treatment in a clinical trial. The company is working to get donanemab approved and on the market as quickly as possible, he said.
And Skovronsky believes the FDA feels the same sense of urgency.
“Every day that goes by, there are some patients who pass through this early stage of Alzheimer’s disease and become more advanced and they won’t benefit from treatment,” he said in an interview with CNBC. “That’s a very pressing sense of urgency.”
Lilly previously applied for expedited approval of donanemab.
The FDA rejected that request in January and asked the company for more data on patients who received the antibody for at least 12 months. Lilly said the data wasn’t available at the time because many patients were able to stop dosing at six months because the treatment cleared plaque quickly.
Nearly half of patients — 47% — who received donanemab showed no disease progression a year after treatment began, compared with 29% who did not receive the antibody, according to the data released Wednesday.
More than half of patients completed the treatment in the first year and 72% completed it in 18 months due to clearance of brain plaque.
In a separate measure, patients who received donanemab showed 40% less decline in their ability to conduct daily activities at 18 months. This means they could better manage finances, drive, pursue hobbies and hold conversations than those who did not receive the treatment.
“These are the strongest phase 3 data for an Alzheimer’s treatment to date. This further underscores the inflection point we are at for the Alzheimer’s field,” said Maria Carrillo, the Alzheimer’s Association chief scientific officer, in a statement.
Brain plaque reduction
Donanemab targets brain plaque associated with Alzheimer’s disease. The treatment significantly reduced the plaque as early as six months after treatment, according to Lilly. Many patients saw such significant reductions that they tested negative for plaque presence on their PET scans, according to the company.
Donanemab cleared the plaque at six months in 34% of patients who had intermediate levels of a protein called tau that can become toxic and kill neurons. At 12 months, donanemab cleared the plaque in 71% of patients with the same tau levels.
“It should be unequivocal that drugs that remove plaque, particularly if you can remove plaque completely and do it quickly, can lead to very significant clinical benefits for patients,” Skovronsky said in an interview.
“The earlier in the disease course you do this, the more you can slow the disease,” he said.
Dr. Eric Reiman, executive director of the Banner Alzheimer’s Institute, said the results do not necessarily mean the plaque is completely gone, but donanemab cleared the plaque to such a degree that the treatment removed measurable evidence of it. The Banner Alzheimer’s Institute had two physicians who participated in the donanemab trial as principal investigators.
Brain swelling and bleeding risk
Donanemab can cause brain swelling and bleeding in patients that in some cases can be severe and even fatal. Three trial participants died from these side effects, according to Lilly.
These types of side effects have been observed in other Alzheimer antibody treatments such as Eisai and Biogen’s Leqembi, which received expedited FDA approval in January.
Reiman said he’s encouraged by the potential clinical benefit to patients but it’s important to be clear about the risks.
“We also need to be clear that there are side effects, including an uncommon but potentially catastrophic risk,” said Reiman. “And we need to continue to do our best to understand what that risk is for individual patients, to inform patients and family caregivers, and do everything we can to mitigate that risk,” he said.
About 24% of patients who received donanemab showed brain swelling on an MRI, but only 6% displayed actual symptoms. About 31% of patients had small brain bleeds called microhemorrhages, compared with 13.6% among patients who didn’t receive the treatment.
Lilly said the majority of the cases of brain swelling and bleeding were mild to moderate and patients stabilized with the right care, but cautioned that serious and life-threatening events can occur. About 1.6% of the swelling and bleeding cases were serious, according to Lilly.
Skovronsky said every patient would need to have a discussion with their doctor that weighs the potential benefits of donanemab with the possible risks.
“On a population basis, our view is its benefits outweigh risks,” Skovronsky said.
“FDA is the steward of that for the U.S.,” he said of the risk-benefit analysis that will determine whether donanemab wins approval.