Landmark approvals in Alzheimer’s disease for Biogen and Eisai’s Leqembi and Eli Lilly’s Kisunla have brought new disease-modifying treatments to patients. And while neither of the amyloid-targeting drugs have garnered as much controversy as their predecessor Aduhelm, it’s unclear if they’ll find blockbuster success.
Leqembi, which was OK’d in 2023, is moving in a positive direction, according to Biogen’s most recent earnings report. Between April and June, sales jumped to about $40 million globally — more than double its first three months on the market.
Yet, scrutiny over Leqembi’s minimal efficacy from regulators, payers and physicians has kindled a debate over whether the treatment is worth the costs and safety risks for patients.
As the market awaits initial sales figures for Kisunla following its July approval, this friction between various stakeholders showcases ongoing turbulence in the Alzheimer’s arena.
Are there other signs of hope for Alzheimer’s patients on the horizon? A snapshot of market developments reveals the progress — and setbacks — for drug developers.
Cobenfy’s next big act?
In late September, Bristol Myers Squibb scored the first FDA nod in several decades for a schizophrenia treatment with a new modality. And the drug’s groundbreaking run may not be over.
BMS is also testing the treatment, now called Cobenfy, in Alzheimer’s, and expects phase 3 data in 2026.
It’s a roundabout journey for Cobenfy, which was originally studied in Alzheimer’s but was scrapped in the ‘90s by Eli Lilly due to side effects. Years later, Cobenfy’s therapeutic potential in neuroscience caught the eye of Andrew Miller, who would go on to combine it with another drug that could reduce off-target downsides and launch Karuna Therapeutics to develop it as a schizophrenia treatment. BMS later bought Karuna for $14 billion.
Cobenfy’s more favorable side effect profile is part of why it’s generated so much buzz, and could have major potential on the Alzheimer’s market.
BMS is specifically testing Cobenfy as a treatment for Alzheimer’s disease psychosis — an indication area that, like schizophrenia, is rife with therapies that trigger difficult side effects. If it ultimately wins approval, some analysts estimate it could rake in more sales from Alzheimer’s than schizophrenia, an area where it’s already pegged to become a blockbuster.
Sage’s latest setback
Sage Therapeutics’ ambitions in neuroscience are being challenged from multiple directions — most recently in Alzheimer’s.
Earlier this week, the company announced its experimental drug called SAGE-718 failed to outperform a placebo in a phase 2 study targeting mild cognitive impairment and mild dementia in Alzheimer’s. Sage is now pulling the plug on further development for the drug, an NMDA receptor positive allosteric modulator, in that indication.
The clinical setback follows a phase 2 flop for SAGE-718 in Parkinson’s, which was announced in April. There’s still a chance Sage could pull off a phase 2 win in Huntington’s disease — but after the latest mid-stage failure, analyst expectations are low.
Overall, Sage has had a rough ride in recent years. Although the company scored a historic nod for its oral postpartum depression treatment Zurzuvae in 2023, news that the FDA rejected its bid to win an expanded approval in major depressive disorder drastically reduced the drug’s sales potential. Sage ultimately cut 40% of its staff.
Academic advances that could fuel better drug R&D
In the academic realm, scientists are continuing a push to better understand the underlying drivers of Alzheimer’s disease.
A study published this week shed more light on the glymphatic pathway, which helps the brain remove excess proteins such as amyloid and tau — key hallmarks of Alzheimer’s. Using MRI imaging, the research showed how cerebral interstitial fluid mixes with other fluids and clears soluble byproducts through perivascular spaces — a process that could be hampered in neurological conditions including brain injury and Alzheimer’s.
The study, which the researchers called the first to show this fluid exchange in humans, builds on a growing body of evidence linking slow waste clearance in the brain to Alzheimer’s.
“This shows that cerebrospinal fluid doesn’t just get into the brain randomly, as you put a sponge in a bucket of water. It goes through these channels,” senior author Dr. Juan Piantino said in an Oregon Health & Science University School of Medicine release.
Because the glymphatic pathway is active during sleep, the researchers stressed relaxation techniques and quality slumber to keep the brain healthy. But the new-found ability to measure glymphatic function could also pave the way to developing glymphatic-targeting drugs.
