Updates on Remternetug for Alzheimer Disease
Experts share more on research developments of remternetug for Alzheimer disease.
Matan Dabora, MD, and Kevin Biglan, MD, discussed the investigational monoclonal antibody remternetug and its clinical program, TRAILRUNNER-ALZ-3, for early Alzheimer disease.1
Dabora explained that remternetug targets the pyroglutamate modification of deposited amyloid plaques, promoting their clearance through microglial-mediated phagocytosis.2,3 Consistent with the amyloid-tau-neurodegeneration hypothesis of Alzheimer disease pathogenesis, the drug is designed to interrupt the pathological cascade preceding neurodegeneration by eliminating amyloid burden at its earliest stages. A key differentiator from currently approved amyloid-targeting therapies is its subcutaneous route of administration, which eliminates the need for infusion center visits and avoids infusion-related reactions. Dabora noted that remternetug also demonstrated an absence of immunogenicity, with no anti-drug antibodies observed, supporting its favorable tolerability profile.
Biglan described the LAKI study, which enrolled cognitively unimpaired individuals or those with mild cognitive impairment who have evidence of amyloid pathology confirmed by plasma biomarker. The trial was designed with primary care providers in mind, relying on blood-based diagnostics and standard cognitive assessments to streamline eligibility determination and reduce referral delays. Both speakers emphasized the clinical rationale for early intervention, with Biglan noting that "identifying individuals who are at highest risk for developing symptoms of Alzheimer disease—before they have significant or have no symptoms—allows us to delay or prevent the onset of those symptoms, which has a huge impact on individual quality of life."
Dabora reinforced this position, stating that "when you treat patients that have a higher cognition state at background, or that have minimal cognition impairment, we can delay or slow the disease in a greater way compared to patients who are more far down the road." The LAKI study employs a hybrid design with decentralized elements and centralized outcome raters to minimize site variability and reduce participant burden. A parallel arm within the Dominantly Inherited Alzheimer Network study is also evaluating remternetug in autosomal dominant Alzheimer disease.
Dr Dabora is associate vice president for Alzheimer’s disease clinical development at Eli Lilly.
Dr Biglan is associate vice president at Eli Lilly and adjunct clinical professor of neurology at the University of Rochester.
References
1. A study of remternetug (LY3372993) in early Alzheimer's disease (TRAILRUNNER-ALZ 3). ClinicalTrials.gov. November 20, 2025.
2. Remternetug (LY3372993): a next-generation pyroglutamate-A-Beta monoclonal antibody in Alzheimer's disease. Mind the Gulf.
3. Cummings J, Osse AML, Cammann D, et al.
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