FDA advisers support Eli Lilly's experimental Alzheimer's medication donanemab.
Every year, one in three elderly Americans sadly passes away due to Alzheimer's disease or some other type of dementia, as stated by the Alzheimer's Association. This disease is even more deadly than both prostate and breast cancer combined.
Donanemab is a promising treatment option that helps in removing amyloid plaque formations in the brain, which are a major sign of Alzheimer's disease. These plaque formations are harmful deposits that develop in the brain, causing negative effects on brain functioning. The removal of these plaques appears to slow down the brain changes typical of Alzheimer's.
The drug functions by bonding with the amyloid plaques and catching the attention of the immune system, thus aiding in their removal.
While there's no existing cure for Alzheimer's and there's no drug available to prevent the onset of the disease, Donanemab and Leqembi, another existing drug created by Eisai and Biogen, have shown promise in slowing down the progression of the disease during its early stages.
Lilly informed the FDA's Peripheral and Central Nervous System Drugs Advisory Committee that the late-stage clinical studies demonstrated "significant results" for patients who received Donanemab, as they had a 37% lower chance of disease progression over a period of 1.5 years compared to patients taking a placebo.
The occurrence of severe adverse events was "comparatively minimal," with only 2% of patients experiencing them, and they were the same in all trial groups. The mortality rate was slightly higher in patients receiving Donanemab, being 2.0% compared to 1.7% in the placebo arm of the trial.
However, three patients died due to ARIA, or amyloid-related imaging abnormalities, a form of microhemorrhage.
In clinical trials for Leqembi, which is already available, some patients experienced ARIA, but at a much lower rate than observed in the Donanemab trials. Additionally, Leqembi has also been implicated in patient deaths.
Since most Donanemab patients showing ARIA symptoms did so within the initial six weeks of the study, Lilly added another MRI to the trial in order to check for the issue before providing the second dose. If a patient had asymptomatic ARIA, treatment would be postponed to allow it to resolve without escalating into a more serious or symptomatic condition.
The FDA committee discussed two crucial questions and touched upon three significant topics based on the late-stage clinical trial findings.
The committee voted unanimously for the questions if the data indicated that the drug is an effective treatment for Alzheimer's disease and if the benefits of the drug exceeded the risks in the study population.
The FDA will consider the committee's feedback before making their decision on whether to approve the drug.
Dr. Dean Follmann, the assistant director for Biostatistics at the National Institute of Allergy and Infectious Diseases, and Dr. Kathleen Poston, the director of Stanford Movement Disorders Center, both voted 'yes' because the evidence was "powerful" and "consistent" across different groups.
Sarah Dolan, the acting consumer representative on the committee and a consultant with the Critical Path Institute in Tucson, Arizona, also voted yes and expressed satisfaction with the findings.
The trials encompassed only patients with low-medium tau levels, a protein that can become problematic and contribute to Alzheimer's. To address this, Lilly eliminated patients with no or extremely low tau levels due to the trial's limited duration. These patients were also excluded for high tau levels.
The committee had reservations about applying the results to patients with different tau levels because of the lack of adequate data. Additionally, the FDA expressed concerns about the requirement of a tau PET test before receiving the drug, since it's not widely accessible, making it difficult for some individuals to access it.
The FDA also raised questions about some aspects of ongoing research and factors relating to the possible administration of the drug.
After conducting additional research, Lilly proposed that patients may be allowed to discontinue the drug if they exhibit significant progress. The committee suggested that this would necessitate clear criteria for stopping or renewing the treatment if symptoms reoccurred. The committee also highlighted that there was minimal diversity among the trial participants, with most being Caucasian. They indicated that future studies should aim to include a more diverse population to gain understanding on how the drug operates in various racial demographics.
Previously, the FDA announced this meeting with surprise, as many experts anticipated the drug's approval from the FDA in the previous year.
Dr. Reisa Sperling, a professor of neurology at Harvard Medical School, stated to the committee prior to the voting that the absence of treatments for Alzheimer's exposes the United States to a concerning health threat.
"We're excelling at extending people's lives, but if we don't find a solution for this disease, we could create a health crisis," Sperling stated.
Simultaneously, Lilly mentioned they are researching additional treatments for Alzheimer's.
"Realizing the pressure this disease places on society, we consider it our duty to bring forth a well-defined disease-halting therapy to patients," remarked Dr. David Hyman, Chief Medical Officer at Eli Lilly and Company to the panel.
Lilly sees donanemab as "a vital but ultimately incremental" step in the treatment of Alzheimer's disease. Long term, Hyman added that Lilly aims to create a medication that would treat the disease before any symptoms appear, and they are advancing in the development of this medication.
"People deserve more, and we continue to explore additional approaches to tackle this disease," Hyman concluded.
Following the meeting, Lilly voiced satisfaction with the committee's favorable decision.
"We appreciate the committee's consensus recognition of donanemab's favorable advantage-risk balance," stated Mark Mintun, Lilly's Group Vice President of Neuroscience Research and Development in a press statement. "We're eager to deliver this treatment option."
The Alzheimer's Association championed for the committee's approval of donanemab, lauded the panel's unanimous decision in favor of the drug.
"A future with more approved Alzheimer's treatments is a great stride forward for those suitable for these medications," commented Dr. Joanne Pike, President and CEO of the Alzheimer's Association. "Drug progress is arriving."
USAgainstAlzheimer's, a national non-profit that testified in support of the drug during the public comment period in the meeting, emphasized the urgency and "enormous unmet need" for Alzheimer's treatments.
"If allowed by the FDA, donanemab would become the second medicine on the market to improve the quality of life for people in the early stages of Alzheimer's for an extended period while providing physicians and patients with a new option for their treatment strategies," said George Vradenburg, Chair and Co-founder. "We're thankful for the committee's endorsement of this promising therapy."
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The FDA's consideration of Donanemab's approval hinges on whether the drug's benefits outweigh its risks, as stated during the FDA committee meeting.In the clinical trials for Donanemab, some patients experienced ARIA, or amyloid-related imaging abnormalities, which resulted in three patient deaths.
