A new experimental Alzheimer’s drug called donanemab is generating major excitement as a potential breakthrough in treating the disease. In a large-scale clinical trial sponsored by pharmaceutical company Eli Lilly, the antibody-based medicine was shown to slow the decline in memory, thinking, and reasoning skills that are the hallmarks of Alzheimer’s.
While not a cure, donanemab offers new hope for patients in the early stages of the disease by clearing away harmful protein deposits called amyloid plaques that build up in the brain. This provides important confirmation that removing these plaques can change the course of Alzheimer’s if treatment is started early enough.
The 1,736-person trial found the drug slowed the pace of cognitive decline by around 30% on average after 18 months of monthly infusions. This bought precious extra time for patients to hold on to everyday abilities like engaging in conversation, pursuing hobbies, and answering the phone. The benefits were even more pronounced at around 40% for patients with early-stage disease who researchers determined would be more likely to respond to treatment.
However, donanemab is not without risks. About a third of patients experienced swelling of the brain, medically known as amyloid-related imaging abnormalities or ARIA, which in a small number of cases proved fatal. This means careful monitoring for side effects will be essential if the drug is approved for wider clinical use.
Researchers caution more work is still needed to understand donanemab’s effects over the long term. The benefits were modest for some patients in the trial and it’s unclear if they will continue over an extended period. Other drug candidates have failed in late-stage testing despite early promise.
But overall, experts hail these results as a major milestone after decades of disappointment in the quest to find an effective Alzheimer’s treatment. Patient advocacy groups are now urging health systems to urgently prepare for increased demand if donanemab and similar drugs in development are approved in coming years. In the UK, the national health service has already begun assessing donanemab to determine its potential for inclusion.
This work represents hope that science is finally turning the tide against the Alzheimer’s epidemic through advanced drugs that target the underlying disease process. Each new therapy that can slow progression brings us one step closer to the goal of making dementia treatable and saving minds.
Background on Alzheimer’s Disease
Alzheimer’s disease is the most common cause of dementia, affecting over 50 million people worldwide. It is a progressive brain disorder that destroys memory, thinking skills, and the ability to carry out basic daily activities.
In Alzheimer’s, abnormal levels of amyloid beta protein clump together to form plaques that collect between neurons and disrupt cell function. This leads to inflammation and eventual neuron death. As more neurons die, the brain shrinks dramatically.
Genetics, lifestyle factors like exercise, cognitive activity, and diet may influence a person’s risk. Age is the biggest risk factor, with most cases occurring after age 65. Some rare, inherited forms can strike as early as age 30.
Early symptoms include forgetfulness, losing track of time, getting lost in familiar places, and difficulty finding words. As Alzheimer’s advances, memory gaps grow more severe and significant impairment of daily living skills emerges. In late disease, people lose ability to communicate, fail to recognize loved ones, and become bed-bound.
Alzheimer’s typically progresses slowly over 7 to 10 years. Currently only about 200,000 people in the U.S. are estimated to be in the early stages of Alzheimer’s dementia where new drugs like donanemab are believed to be most effective.
Developing effective treatments has proven extremely challenging over the past 20 years. Out of over 400 drug candidates, virtually all have failed in clinical trials. The last Alzheimer’s drug was approved in 2003.
But researchers say donanemab and similar drugs now in development represent a turning point. They offer confirmation that clearing amyloid plaques early on may change the course of the disease. Ongoing work focuses on identifying candidates sooner and starting treatment as early as possible.
Details on the Donanemab Clinical Trial
The Phase 2 clinical trial of donanemab published in July 2022 was known as TRAILBLAZER-ALZ. It involved 1,736 volunteers ages 50 to 85 with early symptomatic Alzheimer’s across 222 sites in North America, Europe, Asia and Australia.
Participants were randomly assigned to receive either donanemab or a placebo via intravenous infusion every 4 weeks for 76 weeks. Donanemab works by binding to aggregated amyloid plaque and triggering the body’s immune system to clear it away.
The primary goal was to measure how donanemab affected cognition and function compared to placebo over 18 months based on two rating scales. Secondary goals included assessing donanemab’s impact on amyloid plaque levels in the brain compared to placebo.
In the donanemab group, 68% met the threshold for substantial plaque reduction after treatment. More plaque clearance was associated with greater slowing of clinical decline. Total plaque clearance was achieved in 25% of the treatment group after just 6 months.
Overall, donanemab slowed 32% of cognitve and functional decline compared to placebo. The effects were greatest in patients with early Alzheimer’s and less brain amyloid – about a 45% reduction in decline based on imaging and clinical factors.
Safety issues included ARIA brain swelling in 37% of the donanemab group. Symptomatic ARIA was seen in 13% of treated patients. There were two deaths judged to be from ARIA.
Next Steps for Donanemab
Based on these positive results, Eli Lilly plans to file for FDA approval for donanemab in early 2023 under the accelerated pathway for drugs that address serious conditions. The data will also form the basis for submissions to regulatory agencies in Europe, Japan and elsewhere.
If approved, experts say questions will center on which group of Alzheimer’s patients should receive the drug. Younger patients with milder disease and less amyloid buildup are likely to derive the most benefit based on this data. Appropriate patient selection and monitoring will be key.
In the UK, the NHS has begun evaluation to determine donanemab’s potential placement in its national treatment guidelines. Cost-effectiveness for the health system will be assessed. The price when launched is estimated at around $27,000 per year.
Alzheimer’s experts hope donanemab’s impact will continue to increase over longer treatment periods beyond this 18-month trial. Combination therapy with other anti-amyloid drugs like lecanemab may also offer synergistic effects. Ongoing research aims to expand initial promising findings.
While incremental, these results offer real encouragement that science is now advancing after years of setbacks. Donanemab provides hope that Alzheimer’s can eventually shift from an untreatable to a manageable condition, especially when caught early enough. Each new therapy takes us closer to that goal.
