Navacaprant

iStock, Makhbubakhon Ismatova These five upcoming data drops could usher in more effective and convenient therapies for Alzheimer’s disease and open up novel pathways of action to treat the memory-robbing illness. A lot has changed in the Alzheimer’s disease space in the last few years. The first-ever disease-modifying drug approved for Alzheimer’s, Biogen and Eisai’s Aduhelm, was discontinued less than two years after its controversial approval . Rising to take its place is Leqembi —the partners’ second anti-amyloid antibody for the disease—which in July 2023 made history as the first Alzheimer’s therapy to win full FDA approval . Eli Lilly’s Kisunla —also an amyloid-targeting antibody—followed a year later. But Alzheimer’s remains a difficult case to crack. There remains a critical unmet need for safe and effective therapies to address Alzheimer’s disease. According to the Alzheimer’s Foundation’s report on the disease, more than 7 million people in the U.S. aged 65 and up have dementia due to Alzheimer’s disease, for an overall prevalence rate of 11%. This figure is likely even higher, given that many patients with Alzheimer’s, especially those with early-stage and mild disease, are often missed by prevalence studies, the foundation states. And as the U.S. population ages in the coming years, the number of people with Alzheimer’s dementia is expected to climb even further. To fill the need, many companies—both those established in the space and those looking to break in—are aiming to push the boundaries in terms of efficacy, patient experience and mode of action. Biogen and Eisai, for example, are proposing a subcutaneous maintenance formulation of Leqembi. The FDA is expected to release a verdict on or before Aug. 31. If approved, Biogen CEO Chris Viehbacher said during the company’s Q4 2024 earnings call that subcutaneous Leqembi would start making an impact on product sales in the back half of this year. The partners are also planning to application for a subcutaneous version for Leqembi induction next year. Here, BioSpace looks at five upcoming data readouts to watch in the Alzheimer’s space. Novo Positions Semaglutide as Alzheimer’s Therapy Two late-stage studies of Novo Nordisk’s best-selling GLP-1 semaglutide, marketed for weight loss as Wegovy, are expected to read out in September, and if results are favorable, it could open up new market opportunities for one of the hottest therapeutic modalities in biopharma. The Danish drugmaker is currently running the Phase III EVOKE and EVOKE Plus trials, studying the potential of semaglutide to reduce cognitive decline and impairment in Alzheimer’s disease. The studies are nearly identical but for different inclusion criteria. EVOKE Plus allowed the participation of patients with significant small vessel involvement, while EVOKE did not. GLP-1 drugs are best known for their metabolic benefits: helping to control blood sugar levels, slowing the movement of food through the stomach and suppressing appetite. But recently, evidence has been mounting that GLP-1s could also have some therapeutic benefit in other disease areas, including Alzheimer’s . In October 2024, for instance, a real-world study in patients with type 2 diabetes linked semaglutide to a 40% to 70% drop in being diagnosed with Alzheimer’s. Similarly, a study published just last week found that semaglutide, as well as Eli Lilly’s GLP-1 tirzepatide (Zepbound for weight loss), is associated with significantly lower risks of dementia and stroke . Novo has also generated promising clinical evidence for GLP-1s in this indication. Phase IIb data released in June last year showed that liraglutide—a predecessor of semaglutide that belongs to the same drug class— can slow the decline of brain function by 18% versus placebo in patients with mild Alzheimer’s disease. Cognitive function was assessed according to a variety of domains, including memory, language and comprehension. On a mechanistic level, it’s not yet clear how GLP-1s would address the underlying pathology of Alzheimer’s, though there is a growing body of evidence linking insulin resistance with the neurodegenerative disorder. Some have even dubbed Alzheimer’s “ type 3 diabetes. ” EVOKE and EVOKE Plus should help to better elucidate this relationship. Eli Lilly Approaches 2026 Readout for Kisunla’s Successor Further out on the readout horizon is a Phase III study of Eli Lilly’s anti-amyloid antibody remternetug, which is expected to return data by March 2026 . The pharma is currently testing remternetug in the late-stage TRAILRUNNER-ALZ 1 trial, which enrolled more than 1,600 patients with early but symptomatic Alzheimer’s disease. The study is assessing both subcutaneous and intravenous formulations of the drug and comparing it against placebo, looking primarily at the clearance of amyloid plaques. Interim Phase I data presented in April 2023 showed that at 85 days, remternetug lowered beta-amyloid plaques in patients with mild-to-moderate dementia due to Alzheimer’s. Remternetug cleared plaques in 18 of 24 patients given three of the drug’s highest doses. As for safety, 10 treated patients in the Phase I study developed amyloid-related imaging abnormalities (ARIA-E) associated with fluid accumulation in the brain. Remternetug is Lilly’s successor to Kisunla. Earlier this month, the regulator signed off on an updated label for Kisunla, allowing a more gradual titration that according to the pharma lowered ARIA-E rates versus its original dosing. Remternetug works by targeting an amyloid-beta precursor, but specifically binding to a certain part that is present only in plaques found in the brain. Aside from TRAILRUNNER-ALZ 1, Lilly is also studying the asset in TRAILRUNNER-ALZ 3 , a Phase III placebo-controlled trial comprising 1,200 patients with early Alzheimer’s disease. The study is currently enrolling participants. BMS Looks To Expand Cobenfy Into Alzheimer’s Psychosis After Schizophrenia Stumble Bristol Myers Squibb is studying its antipsychotic drug Cobenfy as a treatment for psychosis associated with Alzheimer’s disease. The trial has a completion date of July 31 and a readout is expected in the back half of this year . The Phase III study, dubbed ADEPT-2 , compares Cobenfy against placebo in approximately 400 patients with mild to severe Alzheimer’s who have moderate to severe psychosis attributed to the disease. The study’s primary endpoint is the change in hallucinations and delusions, while effects on agitation will be assessed as a secondary outcome. That BMS is testing Cobenfy—which was first approved in September 2024 for schizophrenia—in Alzheimer’s disease should perhaps come as no surprise. After all, the drug has its roots in a molecule called xanomeline, an acetylcholine receptor that Eli Lilly and Novo Nordisk were testing in the mid-1990s as a treatment for Alzheimer’s. It was only in the late 2000s that a biotech called Karuna Therapeutics came onto the scene to combine xanomeline with a muscarinic blocker to minimize side effects, yielding the drug that would eventually become Cobenfy. BMS acquired Karuna for $14 billion in December 2023. The pharma’s Alzheimer’s push follows a Phase III disappointment for Cobenfy, which failed to significantly improve positive and negative symptoms in adults with inadequately controlled schizophrenia. The drug likewise missed key secondary outcomes, including social and personal performance. ProMIS Eyes Early Data for Anti-Amyloid Antibody in 2026 Among the smaller players innovating in the Alzheimer’s space is ProMIS Neurosciences, which is advancing the investigational therapy PMN310. The asset is currently in Phase Ib testing, with interim data expected in the top half of 2026 . PMN310 is a humanized IgG1 monoclonal antibody that works by selectively targeting soluble amyloid-beta oligomers, which according to ProMIS are “the most toxic and pathogenic form” of amyloid-beta. At the same time, the molecule is also designed to avoid amyloid-beta monomers and plaques. Such an approach could help maximize efficacy and safety, according to the biotech’s website . “Only misfolded oligomers are toxic,” ProMIS noted. “Studies indicate that safe and effective antibody therapies for [Alzheimer’s disease] will be those that selectively target and bind only to misfolded oligomers while avoiding any binding to monomers and/or plaque forms of amyloid.” The Phase Ib PRECISE-AD trial started dosing the first patients in February. Phase Ia findings, presented in October 2024, showed that PMN310 was generally well-tolerated in doses reaching up to 40 mg/kg. Results also demonstrated that the antibody was able to cross the blood-brain barrier in healthy volunteers. Pharmacokinetic data pointed to a dose-dependent effect and suggested that even monthly administrations could lead to “adequate” target engagement, as per the company’s release at the time. ProMIS anticipates that PMN310 could be a best-in-class therapy for Alzheimer’s, as per its website . Neumora Targets Year-End Readout for Alzheimer’s Agitation Drug If all goes well, Neumora Therapeutics expects to release Phase Ib data for its investigational drug, NMRA-511, being developed to treat agitation associated with Alzheimer’s disease, by the end of the year . Designed to be orally available, NMRA-511 is a potent blocker of the vasopressin 1a receptor, which according to a company presentation plays a role in regulating the aggression, stress and anxiety responses. NMRA-511 is highly selective for the 1a subtype of vasopressin receptors, setting it apart from other inhibitors in this drug class and potentially giving it what Neumora believes is a “best-in-class” pro this indication. Preclinical data presented in January showed that marmosets treated with NMRA-511 had activity in brain regions that are known to regulate mood and anxiety. The drug also eased anxiety-related behaviors in these primates. Additionally, healthy human volunteers given NMRA-511 likewise demonstrated increased activity in the brain’s frontal region on electroencephalography scans. Neumora launched its Phase Ib signal-seeking trial of NMRA-511 in June 2024, aiming to enroll around 100 participants. The first part of the study was set to focus on healthy elderly adults while the second part would involve patients with agitation associated with dementia in Alzheimer’s disease. A lot is riding on this early-stage study, especially after Neumora’s lead asset navacaprant, a kappa opioid receptor, flopped in a late-stage trial in January, pushing the biotech to suspend two other Phase III studies of the drug. Another of Neumora’s assets, the schizophrenia drug NMRA-266, was placed under clinical hold in 2024 after safety signals in rabbits.