The full clinical trial results for the Alzheimer's therapy donanemab were released on Monday, sparking both hope and caution among experts. Donanemab is an antibody that binds to a protein in the brain called amyloid, which is believed to be connected to Alzheimer's disease. The trial, which involved over 1700 participants, found that after 18 months, those who received the treatment had less progression of their dementia symptoms compared to those who received a placebo. The symptom scores for the treated group were approximately 30% lower than the placebo group overall.
While this may seem like positive news, some doctors are urging caution. Concerns have been raised about the relatively small benefits of the drug, potential fatal side effects, and the practical challenges of providing brain scans to all potential beneficiaries. Additionally, doctors question whether the degree of slowed deterioration would be noticeable to people with Alzheimer's or their families.
One analysis, conducted in collaboration with the drug's manufacturer, Eli Lilly, suggested that a treatment would need to produce at least a 1-point difference on a symptom rating scale to have a noticeable effect. The donanemab trial only showed a 0.7-point difference between the treatment and placebo groups. However, Eli Lilly has argued that the 2019 analysis focused on individual differences, not the overall effects on groups of people.
One group that did see a potentially greater benefit from the treatment was those in the earliest stages of dementia, classified as having mild cognitive impairment. An analysis of the trial results presented at a conference showed a 60% difference between the treatment and placebo groups in this subgroup. However, this analysis has not yet been published in a peer-reviewed paper, making it difficult to interpret.
Another concern raised is the capacity of health systems to handle the requirements of the treatment. Before treatment can begin, patients need a PET scan to reveal amyloid levels in the brain, and the treatment itself must be administered via infusion at a clinic once a month. Regular brain scans are also necessary to monitor for dangerous side effects.
Speaking of side effects, brain swelling was observed in 24% of those who received the treatment compared to 2% in the placebo group. This can be a result of antibodies binding to amyloid in the walls of the brain's blood vessels.
The availability of donanemab will depend on regulatory decisions in different countries. In the US, a decision by the Food and Drug Administration is expected by the end of the year. However, in countries with cost-conscious health systems like the UK, cost-effectiveness assessments will also need to be conducted before the drug can be used within national healthcare services.
Given the relatively small benefits and the potential high costs associated with providing brain scans and infusions, the future of donanemab remains uncertain.