Although about 6.5 million Americans have Alzheimer’s disease, not every drug in development can treat every patient. biogenic (IBIB) investors may learn this lesson the hard way.
Promising results from Alzheimer’s disease drug candidate closely watched by Biogen and Eisai (ESALY) end of September added tens of billions of dollars to their market capitalizations. If investors count the market gains of peers such as Eli Lily (THERE IS) , which have similar drug candidates in development, then the number is significantly higher. Some of these gains may not prove to be sustainable over the long term.
A STAT News report reveals that one patient death occurred in the study led by Eisai. Doctors and regulators are still trying to determine if the death was caused by the experimental therapy, but the report starts an important conversation about the nuances involved in drug development for Alzheimer’s disease.
Can drugs improve the cleaning of waste in the brain?
Healthy brains eliminate cellular waste during sleep. These waste disposal processes become less efficient with age, primarily due to age-related disturbances in sleep quality. This can cause certain areas of the brain to accumulate waste products that form plaques, including those with a protein called beta-amyloid.
Although these plaques are known to accumulate in people with dementia and Alzheimer’s disease, they have not been shown to cause neurodegenerative diseases. They seem to impact communication between neurons, but it’s unclear whether removing the plaques will reverse past damage. Nevertheless, these observations have been the basis for the design of drugs capable of clearing up plaques in the brains of people with dementia and Alzheimer’s disease.
Biogen and Eisai’s anti-plaque drug candidate 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 people with early-stage Alzheimer’s disease who received treatment with lecanemab or a placebo for 18 months.
Anti-plaque drugs are not without risk
The results were promising, but still left room for debate among doctors. Were the results clinically significant? Was the scale used to determine cognitive decline intended to be used in this way? Even critical doctors have said they would prescribe the drug candidate to patients if it gains regulatory approval.
This does not mean that all patients with Alzheimer’s disease would be eligible for treatment. Individuals should have disease at an early stage. Also, people at high risk of brain swelling and brain hemorrhage could be excluded. This is a common side effect among anti-plaque medications.
- Investigators found that 21% of people given lecanemab had brain inflammation or hemorrhage, while only 9% of those given a placebo had the same symptoms.
- A recent study of Eli Lilly’s donanemab found that 27% of people receiving the experimental therapy experienced fluid buildup in the brain.
The STAT News report revealed that a person receiving lecanemab died after suffering a brain hemorrhage. An investigator concluded that the drug candidate was responsible for the death, while Eisai argued that other factors could have contributed.
This highlights a challenge for anti-plaque drugs. For lecanemab and donanemab, most patients who experienced brain inflammation and brain bleeding had no symptoms. Those who did were most likely to report headaches and confusion. This does not necessarily mean that asymptomatic people are not at risk of further complications.
From a clinical perspective, it could be difficult to cost-effectively or effectively monitor individuals for brain inflammation and brain bleeding. These symptoms are usually only confirmed by expensive brain imaging procedures, which cannot realistically be performed on thousands or millions of individuals.
A single death is unlikely to derail regulatory approval. However, this suggests that the patient population eligible for treatment could be much smaller than expected. Physicians and regulators are likely to develop criteria to better determine eligibility and monitor patients receiving anti-plaque drugs, but this could be a slow and evolving process.
For now, investors will be eagerly awaiting the FDA’s approval decision which is expected by January 6, 2023.