Currently, there are five Alzheimer’s drugs approved by the U.S. Food and Drug Administration (FDA) that treat the symptoms of Alzheimer’s disease — temporarily helping memory and thinking problems — with a sixth drug available globally. However, these medications do not treat the underlying causes of the disease or slow its progression.
Many drugs in development aim to interrupt the disease process itself by impacting one or more of the brain changes associated with Alzheimer’s. These changes offer potential targets for new drugs to slow or stop the progress of the disease. Researchers believe successful treatment will eventually involve a combination of medications aimed at several targets, similar to current treatments for many cancers and AIDS.
The following are examples of promising targets for next-generation drug therapies under investigation in current research studies:
Current drugs in research that targets beta-amyloid: CAD106 and CNP520
Two anti-amyloid compounds – CAD106, an active immunotherapy, and CNP520 – are being studied to determine if they can prevent or delay the emergence of symptoms of Alzheimer’s among higher-risk cognitively healthy older adults who have two copies of the e4 type of the APOE gene, one from each parent. The two studies, known as the Alzheimer’s Prevention Initiative (API) Generation Study 1 and Generation Study 2, will determine whether the drugs can combat the accumulation of the protein fragment beta-amyloid into the amyloid plaques that are a hallmark of Alzheimer’s. Plaques form between nerve cells (neurons) in the brain and interfere the with neuron-to-neuron communication that enables the brain to store new information. The studies are expected to conclude in 2025.
One of the enzymes that clips APP, BACE makes it possible for beta-amyloid to form. Therapies that interrupt this process may reduce the amount of beta-amyloid in the brain and ultimately intervene in the development of Alzheimer’s disease.
Current drug in research that targets beta-secretase: JNJ-54861911.
JNJ-54861911 inhibits the ability of the beta-secretase enzyme to make beta-amyloid. It is currently in a Phase 3 study to determine if it slows cognitive decline in people who do not have Alzheimer’s symptoms but have elevated levels of beta-amyloid in the brain. The study is expected to be completed in 2024. JNJ-54861911 is administered in pill form. (Drug is still in research; not available to the public.)
Current drug in research that targets tau protein: AADvac1
AADvac1 is a vaccine that stimulates the body’s immune system to attack an abnormal form of tau protein that destabilizes the structure of neurons. If successful, it has the potential to help stop the progression of Alzheimer’s disease. A Phase 2 clinical trial, called ADAMANT, enrolled 208 volunteers living with mild Alzheimer’s disease began in March 2016 and was completed in June 2019. Initial results were announced in September 2019 and showed that 98.2% of participants who were given the vaccine generated antibodies to the tau protein. The results also showed no difference in adverse events between the treatment and control groups, meaning that the treatment was well tolerated. The change in several biomarkers for Alzheimer’s disease showed trends that suggest AADvac1 may slow the progression of the disease. The slowing of the progression was also supported by positive changes in several cognitive endpoints. Based on the results, the vaccine will continue to be studied in the next level of clinical trials. (Drug is still in research; not available to the public.)
Current drug in research that targets inflammation: Sargramostim
Approved by the FDA for bone marrow stimulation in people with leukemia, Sargramostim stimulates the innate immune system. It is being tested in Alzheimer’s because it may stimulate immune processes that could protect neurons in the brain from toxic proteins. A Phase 2 study of Sargramostim is underway. It is expected to be completed in May 2020. (Drug is still in research; not available to the public.)
Current drug in research that targets 5-HT2A: Pimavanserin
Pimavanserin is an inverse agonist for the 5-HT2A receptor. This means that pimavanserin mimics the shape of the serotonin “key” and fits into the 5-HT2A “lock.” However, pimavanserin has the opposite effect of serotonin: it reduces communication between neurons. This may have the effect of reducing the symptoms of dementia-related psychosis. A Phase 3 clinical trial of pimavanserin, called the HARMONY study, met the primary endpoint of the study and was stopped at the preplanned interim analysis by significantly reducing risk of relapse of psychosis by 2.8-fold compared with placebo. The company studying the drug plans to meet with the U.S. Food and Drug Administration (FDA) in the first half of 2020 regarding a supplemental new drug application submission. The FDA previously granted Breakthrough Therapy designation for pimavanserin for the treatment of dementia-related psychosis. Currently, no drug is specifically approved for this indication. (Drug is still in research; not available to the public.)