diranersen (BIIB080) / Biogen, Ionis - LARVOL DELTA

Decoding MAPT Exon 10 Mis-Splicing in FTDP-17: From Pathogenic Mechanisms and Experimental Models to Molecular Therapies. (PubMed, Genes (Basel)) - "Additionally, the review highlights recent Phase 2 trial results, including the Diranersen (BIIB080) tau-lowering ASO, the development of MAPT-targeted RNA therapies, new tau-PET and plasma p-tau biomarkers, and innovative strategies to deliver CNS treatments, including non-invasive approaches. By integrating advances in RNA biology, disease modelling and targeted therapies, the review outlines potential future strategies for treating FTDP-17 and other tau-related disorders."

Journal • Review • Alzheimer's Disease • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration • Movement Disorders • Parkinson's Disease • MAPT

LATE BREAKING SYMPOSIUM 1: Additional biomarker and clinical findings from the Phase 2 CELIA study of diranersen in early Alzheimer's disease (CTAD 2026) - No abstract available

Biomarker • Clinical • Late-breaking abstract • P2 data • Alzheimer's Disease • CNS Disorders

Alternative splicing in Alzheimer's disease: event-level evidence, risk-locus biology, and RNA-based therapeutic perspectives. (PubMed, Gene) - "ApoER2 exon 19 correction provides AD-specific preclinical evidence for splice-event modulation, whereas BIIB080/MAPTRx illustrates the feasibility of CNS antisense oligonucleotide delivery and target-engagement monitoring in patients...Overall, AS should not be viewed as a single pathogenic mechanism in AD. Selected splice events may improve AD risk-locus interpretation, molecular stratification, biomarker development, and the design of RNA-based therapeutic strategies."

Journal • Review • Alzheimer's Disease • CNS Disorders • APOE • CD33 • MAPT • TARDBP

From Target Engagement to Translational Disconnect: A Systematic Review and Narrative Synthesis of Direct Tau-Targeted Clinical Trials in Alzheimer's Disease and Primary Tauopathies. (PubMed, Pharmacol Res) - "Tau-targeted therapies highlight a translational gap between biological activity and clinically meaningful benefit across multiple therapeutic mechanisms. Emerging evidence suggests that disease-stage timing, biomarker interpretation, tau heterogeneity, and aging-related factors may contribute to this disconnect. Future strategies will likely require earlier, and more biologically stratified intervention approaches, improved biomarker validation, and combination paradigms addressing the multifactorial complexity of neurodegenerative disease."

Journal • Review • Alzheimer's Disease • CNS Disorders • Movement Disorders • Progressive Supranuclear Palsy

Biogen Presents Phase 2 CELIA Data at AAIC Demonstrating Meaningful Clinical Outcomes and Robust Tau Reduction with Diranersen in Early Alzheimer’s Disease (Biogen Press Release) - "Clinical outcomes: Diranersen demonstrated efficacy across all studied doses at 18 months, with consistent results across multiple prespecified clinical endpoints; the 60 mg dose showed the strongest response with slowing of clinical decline on the cognitive endpoints—42% on ADAS-Cog13 and 50% on MMSE—alongside a 26% slowing on CDR-SB; Biomarker response: Diranersen is the first tau-directed therapy to demonstrate robust reductions in both CSF total tau, with mean reductions of 50–65%, and brain tau pathology, as measured by PET, across all studied doses in a Phase 2 study; Dose response: CDR-SB results favored diranersen versus placebo across all studied doses; higher doses were not associated with greater slowing of decline....Additional analyses and data from CELIA and the ongoing long-term extension study will be presented at future scientific conferences."

Biomarker • P2 data • Alzheimer's Disease

Diranersen: "60mg Q24W demonstrated a promising efficacy profile across multiple endpoints"; Alzheimer's Disease (Biogen) - AAIC 2026: Most AEs were mild or moderate in severity, and did not result in study drug withdrawal"

P2 data • Alzheimer's Disease • CNS Disorders

Biogen to present Phase 2 CELIA data for diranersen at AAIC (Scanx) - "The featured presentation on diranersen will include clinical, biomarker, and safety data from the CELIA study. This 18-month Phase 2 randomized, double-blind, placebo-controlled, dose-ranging study evaluated the efficacy, safety, and tolerability of diranersen in individuals with early Alzheimer’s disease. The study enrolled 416 participants with mild cognitive impairment due to Alzheimer’s disease or mild Alzheimer’s disease dementia, none of whom had previously received anti-amyloid therapy."

P2 data • Alzheimer's Disease

Topline Results from CELIA: A Phase 2 Study to Evaluate the Tau-Targeting ASO Diranersen (BIIB080) in Patients with Early Alzheimer's Disease (AAIC 2026) - No abstract available

Clinical • P2 data • Alzheimer's Disease • CNS Disorders

CELIA: A Study to Learn About the Safety of BIIB080 Injections and Whether They Can Improve Symptoms of Participants With Mild Cognitive Impairment Due to Alzheimer's Disease (AD) or Mild AD Dementia Between 50 to 80 Years of Age (clinicaltrials.gov) - P2 | N=416 | Active, not recruiting | Sponsor: Biogen | Trial completion date: Jan 2029 ➔ Jun 2028

Trial completion date • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia

Ionis partner Biogen announces topline results from Phase 2 CELIA study of diranersen (BIIB080): first study to show reduction in tau pathology and cognitive benefit in patients with early Alzheimer’s disease (Businesswire) - "Data will be presented at the Alzheimer’s Association International Conference (AAIC) 2026 and other upcoming scientific congresses...Pre-specified analyses of cognitive endpoints demonstrated slowing of clinical decline across all studied doses, particularly in participants receiving the lowest dose of diranersen, 60 mg administered every 24 weeks. Diranersen also demonstrated robust reductions in both cerebrospinal fluid (CSF) tau and tau pathology, as measured by positron emission tomography (PET), across all studied doses, with reductions maintained throughout the dosing period. CELIA did not meet its primary endpoint assessing dose response for change from baseline on the Clinical Dementia Rating–Sum of Boxes (CDR-SB) at Week 76...The safety and tolerability profile of diranersen across all studied doses was generally consistent with the Phase 1b study and the known profile of diranersen to date."

P2 data • Alzheimer's Disease

A Study to Determine the Biodistribution, Safety, and Tolerability of a Microdose of Radiolabeled BIIB080 Co-administered With BIIB080 in Healthy Adults (clinicaltrials.gov) - P1 | N=5 | Completed | Sponsor: Biogen | Active, not recruiting ➔ Completed

Trial completion

A Study to Determine the Biodistribution, Safety, and Tolerability of a Microdose of Radiolabeled BIIB080 Co-administered With BIIB080 in Healthy Adults (clinicaltrials.gov) - P1 | N=5 | Active, not recruiting | Sponsor: Biogen | Trial completion date: Jul 2026 ➔ Mar 2026

Trial completion date

Exploratory analyses of clinical outcomes from the BIIB080 phase 1b study in mild Alzheimer's disease. (PubMed, Nat Aging) - P1 | "This favorable trend is supported by reported reductions from baseline in brain neurofibrillary tangles measured with tau positron emission tomography. Trial registration: ClinicalTrials.gov identifier: NCT03186989 ."

Clinical • Clinical data • Journal • P1 data • Alzheimer's Disease • CNS Disorders • MAPT

2026 Anticipated Highlights Include (Businesswire) - "Results from FUSION study of ulefnersen for Fused in Sarcoma (FUS) Amyotrophic Lateral Sclerosis (ALS) (Otsuka)...Multiple Phase 2 data readouts, including IONIS-MAPTRx (BIIB080) in Alzheimer’s disease (AD) (Biogen) and new Phase 3 clinical trial initiations."

Clinical data • New P3 trial • Alzheimer's Disease • Amyotrophic Lateral Sclerosis

Drug Development. (PubMed, Alzheimers Dement) - P1, P2 | "The ongoing Phase 2 CELIA trial will assess the efficacy, safety, and tolerability of BIIB080 compared to placebo in participants with early AD."

Biomarker • Clinical • Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia

Biomarkers. (PubMed, Alzheimers Dement) - P1, P2 | "However, these biomarkers are currently measured in CSF only, and evidence for their use as treatment-response measures is limited. Based on emerging tau biomarker advances and biomarker results from BIIB080, this presentation will provide future directions on the use and importance of tau biomarkers for development of therapies targeting tau."

Biomarker • Journal • Review • Alzheimer's Disease • CNS Disorders • MAPT • p-tau181

Biodistribution of radiolabeled MAPT antisense oligonucleotide BIIB080 following intrathecal administration in healthy adults (CTAD 2025) - No abstract available

Clinical • MAPT

A Study to Determine the Biodistribution, Safety, and Tolerability of a Microdose of Radiolabeled BIIB080 Co-administered With BIIB080 in Healthy Adults (clinicaltrials.gov) - P1 | N=5 | Active, not recruiting | Sponsor: Biogen | Recruiting ➔ Active, not recruiting

Enrollment closed

Innovative Phase 1b/2a Trial to Test Anti-Tau Agent BIIB080 in Corticobasal Syndrome (NeurologyLive) - P1b/2a | N=24 | "At the 2025 Alzheimer’s Association International Conference (AAIC)...investigators shared details on a new phase 1b/2a trial testing the safety and preliminary efficacy of BIIB080 (Biogen/Ionis)...as a potential treatment for corticobasal syndrome (CBS)...The study, a 6-month, randomized, double-blind, placebo-controlled trial, will primarily test the safety/tolerability of BIIB080, an antisense oligonucleotide, in a cohort of 24 patients with a clinical diagnosis of CBS...Overall, plasma p-tau217 was elevated in patients with CBS with positive Aß PET results (mean, 0.57 [SD, 0.43] pg/mL) or FTP PET (mean, 0.75 [SD, 0.30] pg/mL) to concentrations comparable to control individuals with AD (mean, 0.72 [SD, 0.37]), whereas PSP-RS and nfvPPA showed no increase relative to control....Results from CELIA are expected to come in 2026, according to Biogen."

P1/2 data • P2 data • Alzheimer's Disease • CNS Disorders • Dementia

BIIB080: the development of a tau-targeting antisense oligonucleotide in early AD (ASGCT 2025) - "Supported by the Neurologic and Opthalmic Committee"

PET imaging of antisense oligonucleotide distribution in rat and nonhuman primate brains using click chemistry. (PubMed, Sci Transl Med) - "The approach was evaluated in cynomolgus macaques using both the Malat1 test ASO and a candidate therapeutic ASO, BIIB080, targeting the microtubule-associated protein tau (MAPT) gene. PET imaging showed favorable tracer kinetics and specific binding to both ASOs in nonhuman primate (NHP) brain in vivo. These results suggest that the PET imaging tracer [18F]BIO-687 could show the distribution of intrathecally delivered ASOs in the rat and NHP brains."

Journal • Preclinical • MALAT1 • MAPT

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of IONIS-MAPTRx in Patients With Mild Alzheimer's Disease (clinicaltrials.gov) - P1 | N=46 | Completed | Sponsor: Ionis Pharmaceuticals, Inc. | Phase classification: P1/2 ➔ P1

Phase classification • Alzheimer's Disease • CNS Disorders

Biogen’s Investigational Tau-Targeting Therapy BIIB080 Receives FDA Fast Track Designation for the Treatment of Alzheimer’s Disease (GlobeNewswire) - "Biogen Inc...announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to BIIB080, an investigational antisense oligonucleotide (ASO) therapy targeting tau, for the treatment of Alzheimer’s disease.... The Phase 2 CELIA study is now fully enrolled, with a data readout expected in 2026."

Fast track • Alzheimer's Disease

A Study to Determine the Biodistribution, Safety, and Tolerability of a Microdose of Radiolabeled BIIB080 Co-administered With BIIB080 in Healthy Adults (clinicaltrials.gov) - P1 | N=5 | Recruiting | Sponsor: Biogen | Not yet recruiting ➔ Recruiting

Enrollment open

Drug Development. (PubMed, Alzheimers Dement) - "A QSP model was developed to integrate therapies targeting Aβ and tau pathologies in AD. The model can be utilized to explore dosing regimens to support the development of combination therapy."

Journal • Alzheimer's Disease • CNS Disorders • Aβ42 • p-tau181