CDER encourages more early-stage therapies
By Patrick E. Clarke Office of Communications, CDER
Every 68 seconds someone gets Alzheimer’s disease, the progressive disorder that damages then destroys brain cells. Since Alzheimer’s can start 10-15 years before it becomes full-blown, treatment during its early stages remains one hope to stem the disease’s course.
“It has been hard to develop drugs that slow the disease – it may be too late once a person is displaying classic symptoms of dementia,” said Dr. Nicholas Kozauer, clinical team lead, Division of Neurology Products, CDER. “We are very open to the prospect of intervening prior to the onset of the more advanced stages of the disease.”
FDA is responding to the needs of all patients with Alzheimer’s disease but there’s a special emphasis on those in the early stages. CDER recently issued a draft guidance, Developing Drugs for Early Stage Alzheimer’s to help sponsors develop Alzheimer’s drugs that treat the disease before there is a severe decline in mental abilities.
The sixth leading cause of death in the United States, “Alzheimer’s is a terrible disease which currently lacks anything beyond medications that have modest symptomatic effects,” said Kozauer.
Currently, there are two types of medications approved by FDA — cholinesterase inhibitors, (Aricept, Exelon, Razadyne, Cognex) and memantine (Namenda) — to treat the cognitive symptoms such as memory loss, confusion, and problems with thinking and reasoning of early Alzheimer's disease.
Science of Alzheimer’s
The criteria for diagnosis of Alzheimer’s disease for clinical trial enrollment were established in 1984. Since then, the ability to use more advanced testing has enabled the field to progress. “And our understanding of biology has improved,” said Kozauer. Research shows that the underlying changes in patients with Alzheimer’s may begin many years before clinical symptoms emerge.
In the body, signals that form memories and thoughts move through an individual nerve cell as a tiny electrical charge. These nerve cells connect to one another at synapses. When a charge reaches a synapse, it may trigger the release of tiny bursts of chemicals called neurotransmitters. The neurotransmitters travel across the synapse, carrying signals to other cells. Scientists have identified dozens of neurotransmitters.
According to the Alzheimer’s Association, the disease disrupts both the way electrical charges travel within cells and the activity of neurotransmitters. Eventually, Alzheimer's disease leads to nerve cell death and tissue loss throughout the brain.
Patients with early stage Alzheimer’s disease display clear symptoms:
- Forgetfulness of recent events
- Impaired ability to perform challenging mental arithmetic — for example, counting backward from 100 by 7s
- Greater difficulty performing complex tasks, such as planning dinner for guests, paying bills or managing finances
- Forgetfulness about one's own personal history
- Becoming moody or withdrawn, especially in socially or mentally challenging situations
As the disease advances, the brain shrinks dramatically, affecting nearly all its functions.
CDER’s guidance was developed to correspond with current research about Alzheimer’s. “We are trying to meet the new science,” said Kozauer. Specifically, the guidance addresses FDA’s current thinking regarding the selection of patients with early Alzheimer’s disease or patients who are determined to be at risk of developing the disease for enrollment into clinical trials.
FDA has the ability to grant drug developers accelerated approval of drugs shown to be reasonably likely to be effective against early-stage Alzheimer’s disease; this provides a fast track for the approval or testing of medications for truly life-threatening diseases.
Kozauer emphasized that the drug being tested must not only show a positive effect in early-stage Alzheimer’s disease patients, but “any positive effect of the drug must also persist, and prove to benefit how a patient functions, as the person continues to takes the drug,” said Kozauer. “Although the approval process is accelerated with these therapies, we are not loosening the FDA standards.”
“With this guidance, we’re offering regulatory flexibility that can help to facilitate the approval of more effective medications that will benefit patients with early Alzheimer’s disease.”