- Patients treated with dunanimab showed a 35% slower decline in memory, thinking and their ability to perform daily activities, according to clinical trial data from its maker, Eli Lilly.
- A monthly infusion of antibodies also significantly reduces brain plaques associated with Alzheimer’s disease.
- Although the results are promising, dunanmap also carries a risk of brain swelling and bleeding that in rare cases can be severe and even fatal.
- Lilly plans to apply for FDA approval of donanemab as soon as this quarter.
Eli Lilly and Company’s pharmaceutical manufacturing plant is pictured at 50 ImClone Drive in Branchburg, New Jersey, March 5, 2021.
Fresh Mike | Reuters
The Alzheimer’s drug Donanemab, designed by Eli Lilly, significantly slowed the progression of the mind-stealing disease, according to clinical trial data released Wednesday by the company.
Eli Lilly data showed that patients who received a monthly infusion of antibodies during an 18-month study showed a 35% slower decline in memory, thinking and their ability to perform daily activities compared to those who did not receive the treatment.
According to the results of the trial, patients who took duanimab were 39% less likely to progress to the next stage of the disease during the study.
However, the benefits of treatment must 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 plans to apply for FDA approval of donanemab as soon as this quarter, according to the company. The trial studied individuals with early-stage Alzheimer’s disease who were confirmed to have brain plaques associated with the disease.
Dunanmap demonstrated the highest level of efficacy of any Alzheimer’s treatment in a clinical trial, said Dr. Daniel Skovronsky, Lilly’s chief scientific and medical officer. He said the company is working to get donanimap approved and brought to market as soon as possible.
And Skovronsky believes the FDA feels the same sense of urgency.
“Every day that goes by, some patients go through this early stage of Alzheimer’s and become more advanced and won’t benefit from treatment,” he said in an interview with CNBC. “This is a very strong sense of urgency.”
Lilly previously applied for expedited approval for donanemab.
The US Food and Drug Administration (FDA) denied that request in January and asked the company to provide 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 doses for six months because the treatment removed plaque so quickly.
Nearly half of the patients — 47% — who received donanimab showed no progression of their disease a 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 in the first year and 72% completed it at 18 months due to cerebral plaque removal.
In a separate measure, patients who received dunanimab showed a 40% lower decrease in their ability to do daily activities at 18 months of age. This means that they can manage finances, drive, pursue hobbies, and carry on conversations better than those who did not receive treatment.
“This is the strongest Phase 3 data for the treatment of Alzheimer’s disease to date. This further underscores the inflection point we are at in the Alzheimer’s field,” Maria Carrillo, chief scientific officer of the Alzheimer’s Society, said in a statement.
Donanemab targets the brain plaque associated with Alzheimer’s disease. According to Lilly, the treatment significantly reduced plaque as early as six months after treatment. Many patients have noticed such significant reductions that they have tested negative for the presence of plaque on PET scans, according to the company.
Donanemab cleared plaque at six months in 34% of patients who had moderate levels of a protein called tau that can become toxic and kill nerve cells. At 12 months, donanimab 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 do it quickly, can lead to very significant clinical benefits for the patient,” Skovronsky said in an interview.
“The earlier you do this in the course of the disease, the more you can slow the disease,” he said.
The results don’t necessarily mean that the plaque is gone completely, but that dunanmap removed plaque to the point that the treatment removed measurable evidence of it, said Dr. Eric Riemann, executive director of the Banner Alzheimer’s Institute. The Banner Alzheimer Institute had two physicians who participated in the donanemab trial as principal investigators.
Donanemab can cause brain swelling and bleeding in patients that can be severe in some cases and even fatal. Three trial participants died from these side effects, according to Lilly.
These kinds of side effects have been seen in other antibody therapies for Alzheimer’s disease such as Eisai’s and Biogen’s Leqembi, which received expedited 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 clear that there are side effects, including risks that are uncommon but potentially catastrophic,” Reimann said. “We need to continue to do everything we can to understand what this risk is for individual patients, to inform patients and their family caregivers, and to do everything we can to mitigate this risk,” he said.
About 24% of patients who received dunanimab showed brain swelling on MRI scans, but only 6% showed true symptoms. About 31% of patients had a small brain bleed called microhemorrhage, compared to 13.6% among patients who did not receive treatment.
The majority of cases of brain swelling and hemorrhage were mild to moderate and the patients’ condition stabilized with appropriate care, Lilly said, but she warned of the potential for serious and life-threatening events. According to Lilly, about 1.6% of cases of swelling and bleeding were serious.
Skovronsky said each patient will need to have a discussion with their doctor weighing the potential benefits of dunanmap against the potential risks.
“On a population basis, we see that its benefits outweigh the risks,” Skovronsky said.
He said of the risk-benefit analysis that will determine whether or not the FDA gets approval.