Full Breakdown
Biogen’s Tau-Targeting Alzheimer’s Drug Shows Promise and Puzzles in Phase 2 Trial
7/14/2026, 10:13:08 PM
Core Event
On July 14 2026, Biogen presented results from the mid-stage “CELIA” trial of its antisense oligonucleotide diranersen (also known as BIIB080 or IONIS-MAPTRx) at the Alzheimer’s Association International Conference in London. The 18-month, double-blind study enrolled 416 participants with mild cognitive impairment or early Alzheimer’s disease and evaluated three dosing regimens: 60 mg intrathecally every six months, 115 mg every six months, and 115 mg every three months. The lowest dose produced a 26 % slower decline on the Clinical Dementia Rating-Sum of Boxes (CDR-SB) scale and achieved a 50-65 % reduction in tau protein levels measured in cerebrospinal fluid and PET imaging. No cases of amyloid-related imaging abnormalities (ARIA) were observed; the most common adverse events were mild to moderate lumbar-puncture pain, headache, and a transient confusional state lasting about a week.
Background & Context
Alzheimer’s disease is driven by accumulation of amyloid plaques and neurofibrillary tangles composed of tau protein. Existing FDA-approved therapies—lecanemab (Leqembi) and donanemab (Kisunla)—target amyloid and modestly slow cognitive decline. Prior attempts to lower tau have failed, largely because they relied on antibodies that bind extracellular tau. Diranersen, developed by Ionis Pharmaceuticals and licensed to Biogen in 2019, uses an antisense mechanism to silence the MAPT gene, reducing production of all tau isoforms both inside and outside neurons. The approach mirrors Ionis’s earlier successes with spinal muscular atrophy (Spinraza) and ALS (Qalsody).
Data & Statistics
- Participants: 416 (Phase 2).
- Tau reduction: 50-65 % across all doses (brain imaging and CSF).
- Cognitive outcomes for the 60 mg dose:
- 26 % slowing on CDR-SB (comparable to amyloid drugs).
- 42 % slowing on ADAS-Cog13.
- 50 % slowing on Mini-Mental State Examination (MMSE).
- 30 % slowing on modified iADRS.
- 23 % slowing on ADCOMS.
- No improvement on ADCS-ADL-MCI (daily functioning).
- Side effects: injection-site pain, headache, transient confusion; no ARIA.
- Market reaction: Biogen shares fell ~7 %; Ionis shares down ~2.5 % after data release.
Official Statements & Responses
Biogen’s head of development, Dr. Priya Singhal, said the company will move forward with a pivotal Phase 3 trial slated to begin in 2027, with results anticipated by 2030-31. Maria Carrillo, chief science officer of the Alzheimer’s Association, called the findings “worth pursuing” despite the missed dose-response goal. The Alzheimer’s Association noted that the strongest cognitive signal emerged from the lowest dose, an “opposite” pattern to the trial’s primary objective. Biogen is consulting a broad panel of Alzheimer’s experts as it prepares the next study.
Criticism & Opposition
Investors expressed skepticism over the lack of a clear dose-response relationship and the modest magnitude of benefit. Analyst Jack Allen highlighted a 0.4-point CDR-SB difference as the threshold for a meaningful effect, which the trial did not achieve. Cantor analyst Joshua Schmidt questioned Biogen’s strategic focus, suggesting the company may be “reopening its past can of worms” when other pipeline assets appear more promising.
Conflicting Reports & Gaps
While most sources report a 26 % slowing on CDR-SB, Reuters noted an ambiguous “26 % or 0” figure, indicating uncertainty about statistical significance. Several secondary endpoints reached only nominal significance, and the trial showed no benefit on daily-function measures, leaving the clinical relevance of the cognitive signals unresolved.
Verbatim Quotes
- “This trial, as far as I'm concerned, is proof of principle. If you change tau, you can change the course of the disease, and we haven't had that before,” — Cath Mummery, professor of clinical neurology, University College London
- “it was the opposite,” — Maria Carrillo, chief science officer, Alzheimer’s Association
- “This is really quite promising if it were to hold up” — Jessica Langbaum, Banner Alzheimer’s Institute
- “This is early days,” — Dr. Reisa Sperling, Mass General Brigham
- “This is really the first time anyone has shown tau reduction … leads to cognitive benefit at an effect that looks comparable to amyloid lowering,” — Diana Gallagher, head of Biogen’s development units for Alzheimer’s, dementia, multiple sclerosis and immunology
What’s Next
Biogen plans a single-arm, pivotal Phase 3 trial of diranersen to start in 2027, enrolling a broader early-Alzheimer’s cohort and incorporating longer follow-up through 2030-31. An extension phase of the CELIA study continues, with over 90 % of completers electing to remain on treatment. Parallel efforts, such as the NIH-funded Alzheimer’s Tau Platform at UCSF, will evaluate additional tau-targeting agents and potential combination strategies with amyloid therapies.
