The mysteries of Alzheimer’s disease are unfolding — not as quickly as patients, physicians and researchers would hope, but at a pace that sets the stage for more robust progress in years to come.
As neuroscience companies take cues from advanced tools in imaging and for biomarkers, they’re learning from the shortcomings of the past. Even commercial failures like Biogen and Eisai’s Aduhelm have helped researchers understand the many complexities of the disease.
Overall, amyloid-beta blockers like the two medications approved in recent years — Eisai and Biogen’s Leqembi and Eli Lilly’s Kisunla — have moved the Alzheimer’s field forward, but not without a shaky balance between benefit and risk that scientists are trying to improve, said Dr. Toby Ferguson, chief medical officer at Voyager Therapeutics, which has an tau-targeting antibody in the early-stage clinic and two gene therapies in the preclinical pipeline.
“The broad point here is that these are effective therapies, but there’s still room to climb — there’s clearly a need for more therapies,” Ferguson said. “Often when you start to see innovations in neurologic disease, the first round of therapies are effective, but not fully effective.”
For Ferguson, who spent more than half a decade at Biogen leading in neuromuscular drug development, the current progress being made in Alzheimer’s hearkens back to the early days of muscular sclerosis. After Biogen’s start with MS interferon treatments like Avonex and Plegridy in the 1990s, which Ferguson said were “modestly effective,” the company was able to advance new products with a better risk-benefit portfolio, such as the blockbuster Tecfidera and its successors — “treatments that can fully suppress disease activity,” he said.
“To transform the disease, you need multiple companies working on multiple targets.”
Dr. Toby Ferguson
Chief medical officer, Voyager Therapeutics
Compared to the progressive evolution of MS drugs, Alzheimer’s therapies are still in the early stages as researchers learn how patients respond in a broader context.
“It opens the door, because what it gives you is a set of tools, and the tools in Alzheimer’s are in a much better state compared to even a few years ago,” Ferguson said, pointing to imaging techniques and more highly tuned biomarkers, as well as a better understanding of the patient population’s needs. “You put these together and you have a tool set which, as a drug developer, allows us to at least know if our drug is having a biologic effect, and hopefully, eventually, a clinical effect.”
Going forward, it will also be critical for the industry to take on diverse targets as a means of capitalizing on multiple paths at once, Ferguson said.
“To transform the disease, you need multiple companies working on multiple targets,” Ferguson said.
And several companies — including Voyager — are aiming at tau as the next target to make an impact on the disease.
The rise of tau
Targeting tau tangles as opposed to amyloid plaques has long been the less prominent approach to Alzheimer’s, but it’s consistently gained steam. While amyloid plaques are an early indicator of the disease, tau potentially holds the key to a deeper connection with cognitive decline.
At Voyager, the clinical work for the antibody VY7523 is still in its infancy but showing promise. Yesterday, the company reported safety and tolerability among healthy patients in a dosing study, as well as secondary endpoints that point to possible efficacy. A second dosing study is ongoing and powered to more clearly reveal how well the antibody clears tau tangles in the brain. That study is set to read out by the end of 2026.
And while an antibody holds a great deal of potential in preventing the spread of proteins like tau in the brain, what if a gene therapy could help prevent the creation of that protein in the first place? That’s where Voyager’s earlier-stage candidate VY1706, an siRNA gene silencing therapy, comes in.
The one-time injection to prevent the onset or worsening of Alzheimer’s could be a big step in the treatment paradigm, said Ferguson. The therapy has shown promise in preclinical studies, said Todd Carter, Voyager’s chief scientific officer. While the company recently announced it would cut an ALS gene therapy program originally slated to read out this year, a move that caused shareholders to panic, the Voyager team has high hopes for VY1706, which employs the same plasmid delivery tech.
As for the future of Alzheimer’s disease, there isn’t just one approach that holds all of the cards as a winning treatment — revealing the secrets of the complicated disease will require multiple shots on goal from multiple companies, Ferguson said.
“One company cannot do all of Alzheimer’s, full stop,” Ferguson said. “You’ll need people to take risks on new targets and different areas of biology, and the winners will be determined by the good experiments.”
