Although an estimated 6.5 million Americans suffer from Alzheimer's disease, not every drug in development can treat every patient. Biogen (BIIB) investors might learn that lesson the hard way.
Promising results from a closely-watched Alzheimer's drug candidate from Biogen and Eisai (ESALY) in late September added tens of billions of dollars to their market caps. If investors count the market gains from peers such as Eli Lily (LLY), who have similar drug candidates in development, then the number is significantly larger. Some of those gains may not prove durable in the long run.
A report from STAT News reveals that a patient death occurred in the Eisai-led study. Doctors and regulators are still trying to determine if the death was caused by the experimental therapy, but the report begins an important conversation about the nuances involved in Alzheimer's drug development.
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Can Drugs Improve Waste Cleanup in the Brain?
Healthy brains clear cellular wastes during sleep. These waste-removal processes become less efficient as we age, primarily because of age-related disruptions to sleep quality. That can cause certain regions of the brain to accumulate wastes that form plaques, including those comprising a protein called beta amyloid.
Although these plaques are known to accumulate in individuals with dementia and Alzheimer's disease, it hasn't been shown that they cause neurodegenerative diseases. They appear to impact communication between neurons, but it isn't known if removing the plaques will reverse past damage. Nonetheless, these observations were the impetus to design drugs capable of clearing plaques in the brains of individuals with dementia and Alzheimer's.
The plaque-clearing drug candidate from Biogen and Eisai is a monoclonal antibody called lecanemab. In a late-stage clinical trial, the experimental therapy was found to slow cognitive decline by 27% compared to placebo. The results were calculated from 1,800 individuals with early-stage Alzheimer's who received treatment with lecanemab or placebo for 18 months.
Plaque-Clearing Drugs Are Not Risk Free
The results were promising, but still left room for debate among doctors. Were the results clinically meaningful? Was the scale used to determine cognitive decline intended to be used in this way? Even critical doctors said they would prescribe the drug candidate to patients should it earn regulatory approval.
That doesn't mean every patient with Alzheimer's would be eligible for treatment. Individuals would need to have early-stage disease. Additionally, those at high risk for brain swelling and brain bleeding might be excluded. It's a common side effect among plaque-clearing drugs.
- Investigators found that 21% of individuals receiving lecanemab experienced brain inflammation or brain bleeding, whereas only 9% of those receiving placebo experienced the same symptoms.
- A recent study of donanemab from Eli Lilly found 27% of individuals receiving the experimental therapy experienced fluid build up in the brain.
The STAT News report revealed that an individual receiving lecanemab died after experiencing bleeding in the brain. An investigator concluded the drug candidate was responsible for the death, while Eisai argued other factors could have contributed.
This highlights one challenge for plaque-clearing drugs. For both lecanemab and donanemab, most patients who experienced brain inflammation and brain bleeding didn't have symptoms. Those that did were most likely to report headaches and confusion. That doesn't necessarily mean asymptomatic individuals are not at risk of further complications.
From a clinical perspective, it could be difficult to cost effectively or efficiently monitor individuals for brain inflammation and brain bleeding. These symptoms are typically only confirmed by expensive brain imaging procedures, which cannot be realistically performed across thousands or millions of individuals.
A single death is unlikely to derail regulatory approval. However, it does suggest the patient population eligible for treatment could be much smaller than expected. Doctors and regulators are likely to develop criteria for better determining eligibility and monitoring patients receiving plaque-clearing drugs, but it could be a slow and evolving process.
For now, investors will be eagerly awaiting the FDA approval decision that's scheduled to occur by Jan. 6, 2023.
