Just three decades ago, in 1993 the U.S. Food & Drug Administration (FDA) approved tacrine—brand name Cognex— as the first treatment for symptoms associated with Alzheimer’s Disease. Over the course of the next decade, just four additional drugs were approved. Despite significant efforts in the research community since then, the number of people in the United States living with Alzheimer’s Disease has skyrocketed to more than 6.7 million.
The explosive growth of the aging population in the United States has only added fuel to the fire, and today roughly one in nine Americans over the age of 65 is living with Alzheimer’s. Against what may seem like insurmountable odds, researchers have now entered what is being hailed as the “era of Alzheimer’s treatment” with major breakthroughs and successful trials occurring on a regular basis. So encouraging are the results of new treatments and research that researchers like myself may be well on the way to both understanding the full progression of the disease, and not only treating, but reversing it.
What is the era of Alzheimer’s treatment and what does it mean for patients?
In the three decades following the release of tacrine, Alzheimer’s researchers tested vaccines and other preventive methods against the disease, discovered the Pittsburgh compound for potential disease monitoring and early detection, began standardizing biomarkers, openly shared clinical trial data to increase the potential for success in the development of therapeutics, and within the past six years, saw multiple historic increases in support funding for research from both private and public entities. And it was the combination of efforts and support in the past thirty years that led to where we are now.
Just two years ago, the FDA approved aducanumab, a breakthrough treatment for Alzheimer’s Disease that was shown in clinical trials to slow the progression of the disease, increasing and extending quality of life for patients with early or mild Alzheimer’s Disease. In 2023, lecanemab became the second Alzheimer’s treatment approved by the FDA for the same purpose, though as of yet, it has shown no signs of disease reversal or significant improvement after 18 months of treatment. There are also multiple additional drugs currently undergoing clinical trials with mixed results. Donanemab, which recently reported initial results from Phase III clinical trials, showed far less clinical decline and decline in the ability to engage in daily activities than any other treatment that has gone through Phase III trials as of yet. However, this effectivity is coming at a cost as donanemab has more side effects, ranging from diarrhea and nausea to urinary tract infections and cerebral microhemmorage. For patients currently living with Alzheimer’s, these drugs offer some hope as they slow the decline of cognitive function in patients with early Alzheimer’s, something that wasn’t a truly viable option until now.
Why has it taken so long to get to the era of Alzheimer’s treatment?
Therapeutics— whether for the treatment of oily skin and acne or the treatment of life-threatening diseases— undergo a rigorous research and development process that currently takes years to successfully navigate. The FDA approval process in the United States typically takes 10 to 12 years from initial development to market. That’s because drugs go through multiple pre-clinical and clinical trial phases in order to ensure not only that they work as intended but also to ensure that the treatments are safe for patients.
Collecting meaningful and accurate data was also difficult in the past as trials require the voluntary commitment of hundreds, if not thousands of individuals. More recently, the FDA has offered accelerated approval for treatments that fill unmet needs for serious illnesses, like Alzheimer’s. This allows patients earlier access to drugs but still holds developers responsible for collecting confirmatory data.
What is the future of Alzheimer’s Disease research and treatment?
Although aducanumab, lecanemab, and donanemab are proving that the deteriorating effects of Alzheimer’s can be slowed, there is still work to be done, and that work is in the reversal of Alzheimer’s. My own company, TrueBinding, is currently researching TB006, a new treatment that has shown a trend of disease reversal in moderate to severe cases. During its one-month phase 2a trial, which concluded in November 2022, patients receiving TB006 demonstrated great improvements in both cognition and functioning, but we recognized that because Alzheimer’s in a chronic disease, a one-month trial may not be enough to prove that the treatment can help everyone long term.
TB006 is now several months into an Open Label Extension (OLE) study, and after three months of treatment trial participants, including those with severe Alzheimer’s Disease, have shown disease reversal or stabilization. What’s more, these results are occurring without significant adverse events, or side effects. TB006 is currently scheduled to begin a phase 2b clinical trial soon, and that research may yield yet additional critical data for not only understanding Alzheimer’s Disease but also on the potential to completely, and perhaps even permanently, reverse its deteriorating effects. This means that while the market is already heavily invested in slowing the progression of the disease, we’re also already working on hopefully curing it.
Decades of research built a deep and unique understanding of Alzheimer’s Disease and how it works. Incredibly, researchers have taken that understanding, research, and data and translated it into multiple breakthrough treatments that are permanently changing not only the current landscape for patients, but their future as well. It may only be years yet before the era of Alzheimer’s treatment becomes the era of curing, or erasing, it.
Dr. Dongxu Sun
Dr. Dongxu Sun is CEO of TrueBinding.