An Eli Lilly and Company pharmaceutical manufacturing plant is pictured at 50 ImClone Drive in Branchburg, New Jersey on March 5, 2021.
Mike Segar | Reuters
Alzheimer’s treatment donanemabwhich is made by Eli Lilysignificantly slowed the progression of the mind-robbing disease, according to clinical trial data the company released Wednesday.
Patients who received the monthly antibody infusion over an 18-month study demonstrated a 35% slower decline in memory, thinking and ability to perform daily activities compared to those who did not. didn’t get the treatment, Eli Lilly’s data showed.
According to the trial results, patients who took donanemab were 39% less likely to progress to the next stage of the disease during the study.
But the benefits of treatment will have to be weighed against the risk of brain swelling and bleeding which can be serious and even fatal in rare cases. Three trial participants died from these side effects.
Lilly is considering applying for Food and drug administration approval of donanemab as early as this quarter, according to the company. The trial studied people in the early stages of Alzheimer’s disease who had a confirmed presence of brain plaque associated with the disease.
Dr. Daniel Skovronsky, scientific and medical director of Lilly, said donanemab demonstrated the highest level of effectiveness of any treatment for Alzheimer’s disease in a clinical trial. The company is working to get donanemab approved and on the market as quickly as possible, he said.
And Skovronsky thinks the FDA feels the same sense of urgency.
“With every passing day, there are patients who go through this early stage of Alzheimer’s disease and become more advanced and they will not benefit from treatment,” he said in an interview with CNBC. “It’s a very pressing sense of urgency.”
Lilly previously requested expedited approval for 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 was not available at the time because many patients were able to stop treatment at six months because the treatment quickly cleared plaque.
Nearly half of patients – 47% – who received donanemab showed no disease progression one year after starting treatment, compared with 29% who did not receive the antibody, according to data released Wednesday. .
More than half of patients completed treatment within the first year and 72% completed treatment within 18 months due to brain plaque removal.
In a separate measure, patients who received donanemab showed a 40% decrease in their ability to carry out daily activities at 18 months. This means they could better manage their finances, drive, pursue hobbies and hold conversations than those who did not receive the treatment.
“This is the strongest phase 3 data to date for an Alzheimer’s disease treatment. It further underscores the inflection point we find ourselves at for the Alzheimer’s disease field,” said Maria. Carrillo, scientific director of the Alzheimer’s Association, in a press release.
Brain plaque reduction
Donanemab targets the brain plaque associated with Alzheimer’s disease. The treatment significantly reduced plaque as early as six months after treatment, according to Lilly. Many patients saw such significant reductions that they tested negative for the presence of plaque on their PET scans, according to the company.
Donanemab cleared 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 plaque in 71% of patients with the same tau levels.
“It should be unequivocal that drugs that remove plaque, especially if you can completely remove plaque and do it quickly, can lead to very significant clinical benefits for the patient,” Skovronsky said in an interview.
“The earlier you do it in the course of the disease, the more you can slow down the disease,” he said.
Dr. Eric Reiman, executive director of the Banner Alzheimer’s Institute, said the results don’t necessarily mean the plaque is completely gone, but donanemab cleared the plaque to such a degree that the treatment eliminated measurable evidence of it. The Banner Alzheimer’s Institute had two physicians who participated in the donanemab trial as principal investigators.
Brain swelling and risk of bleeding
Donanemab can cause brain swelling and bleeding in patients, which in some cases can be serious or even fatal. Three trial participants died from these side effects, according to Lilly.
These types of side effects have been seen in other Alzheimer’s disease antibody treatments such as Eisai and Biogen. Leqembi, which received accelerated FDA approval in January.
Reiman said he’s encouraged by the potential clinical benefit for patients, but it’s important to be clear about the risks.
“We also need to be clear that there are side effects, including a rare but potentially catastrophic risk,” Reiman said. “And we need to continue to do our best to understand what that risk is for individual patients, to educate patients and family caregivers, and to do whatever we can to mitigate that risk,” he said.
About 24% of patients given donanemab showed brain swelling on MRI, but only 6% had actual symptoms. About 31% of patients had small brain bleeds called microhemorrhages, compared with 13.6% in patients who did not receive the treatment.
Lilly said the majority of cases of brain swelling and bleeding were mild to moderate and patients stabilized with the right care, but warned that serious and life-threatening events can occur. About 1.6% of cases of swelling and bleeding were serious, according to Lilly.
Skovronsky said every patient should have a discussion with their doctor that weighs the potential benefits of donanemab against the possible risks.
“On a population basis, our view is that its benefits outweigh the risks,” Skovronsky said.
“The FDA is the steward of this for the United States,” he said of the risk-benefit analysis that will determine whether donanemab wins approval.