An Eli Lilly and Company pharmaceutical manufacturing facility is pictured at 50 ImClone Drive on March 50, 2021 in Branchburg, New Jersey.
Fresh Mike | Reuters
The Alzheimer’s treatment Donanemab, which is manufactured by Eli Lillisignificantly slowed the progression of the mind-numbing disease, according to clinical trial data released by the company on Wednesday.
Patients who received the monthly antibody infusion during an 18-month study showed a 35% slower decline in memory, thinking and their ability to perform daily activities compared to patients who did not receive the treatment, according to Eli’s data Lilly showed.
According to the study results, patients taking donanemab were 39% less likely to progress to the next stage of their disease during the study.
But the benefits of treatment must be weighed against the risk of brain swelling and bleeding, which in rare cases can be serious and even fatal. Three study participants died from these side effects.
According to the company, Lilly plans to apply for Donanemab approval from the Food and Drug Administration later this quarter. The study looked at people in the early stages of Alzheimer’s disease who had a confirmed presence of brain plaques associated with the disease.
dr Daniel Skovronsky, Lilly’s Chief Scientific and Medical Officer, said donanemab has shown the highest efficacy of any Alzheimer’s treatment in a clinical trial. The company is working to get donanemab approved and on the market as soon 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 go through this early stage of Alzheimer’s disease and become more advanced and don’t benefit from treatment,” he said in an interview with CNBC. “It’s a very pressing sense of urgency.”
Lilly previously applied for accelerated approval of donanemab.
The FDA denied that application in January and asked the company for more data on patients who had 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 taking it after six months because the treatment quickly cleared plaque.
Almost half of the patients — 47% — who received donanemab showed no disease progression a year after starting treatment, compared with 29% who did not receive the antibody, according to data released Wednesday.
More than half of the patients stopped treatment in the first year and 72% stopped at 18 months due to brain plaque removal.
In a separate measurement, patients who received donanemab showed a 40% less decline in their ability to perform daily activities after 18 months. This means they are better able to manage their finances, drive, pursue hobbies, and have conversations than those who did not receive treatment.
“This is the strongest Phase 3 data yet for an Alzheimer’s treatment. It further underscores the tipping point we are at in the field of Alzheimer’s disease,” said Maria Carrillo, chief scientific officer of the Alzheimer’s Association, in a Explanation.
Brain plaque reduction
Donanemab targets brain plaques associated with Alzheimer’s disease. According to Lilly, the treatment significantly reduced plaque just six months after treatment. Many patients saw reductions so significant that they tested negative for the presence of plaque on their PET scans, according to the company.
Donanemab cleared plaque after six months in 34% of patients who had intermediate levels of a protein called tau, which can become toxic and kill neurons. At 12 months, donanemab cleared plaque in 71% of patients with the same tau levels.
“It should be clear that drugs that remove plaque, especially if you can remove plaque completely and quickly, can result in very significant clinical benefits for the patient,” Skovronsky said in an interview.
“The earlier in the disease process you do this, 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 an extent that the treatment eliminated measurable evidence of it. Banner Alzheimer’s Institute had two physicians who were principal investigators in the donanemab study.
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Brain swelling and risk of bleeding
Donanemab can cause brain swelling and bleeding in patients, which in some cases can be serious and even fatal. According to Lilly, three study participants died from these side effects.
This type of side effect has been seen with other Alzheimer’s antibody treatments like Eisai’s and Biogen’s Leqembi, which received accelerated FDA approval in January.
Reiman said he’s encouraged by the potential clinical benefits for patients, but it’s important to be clear about the risks.
“We also need to be aware that there are side effects, including an unusual but potentially catastrophic risk,” Reiman said. “And we must continue to do our best to understand what that risk is for individual patients, to educate patients and caregivers, and to do what we can to mitigate that risk,” he said.
About 24% of patients receiving donanemab showed brain swelling on MRI, but only 6% showed actual symptoms. Around 31% of patients had small bleedings in the brain, called microbleeds, compared with 13.6% of patients who did not receive the treatment.
Lilly said most cases of brain swelling and bleeding are mild to moderate and patients stabilize with the right care, but cautioned that serious and life-threatening events can occur. According to Lilly, about 1.6% of cases of swelling and bleeding were serious.
Skovronsky said every patient needs to have a conversation with their doctor, who will weigh the potential benefits of donanemab against the possible risks.
“On a population basis, in our view, the benefits outweigh the risks,” Skovronsky said.
“The FDA is the US steward for this,” he said of the risk-benefit analysis that will determine whether donanemab receives approval.