Tau therapy cuts brain tau up to 65%

Biogen reported on July 14 that its experimental tau-targeting drug diranersen showed both biomarker reductions and slower clinical decline in a mid-stage Alzheimer’s trial, adding one of the clearest human signals yet for a tau-directed therapy. The data came from the Phase 2 CELIA study in people with early Alzheimer’s disease and were presented at the Alzheimer’s Association International Conference in London. (alz.org) The company said the drug reduced tau measured in cerebrospinal fluid and on brain imaging, while prespecified clinical analyses favored diranersen over placebo across studied doses. (investors.biogen.com) Biogen said it plans to take the drug into Phase 3 testing. ### What exactly did the CELIA trial show? The Phase 2 CELIA study tested diranersen, also known as BIIB080, in people with early Alzheimer’s disease over 18 months. (investors.biogen.com) Biogen described it as a randomized, placebo-controlled, dose-ranging trial of an antisense oligonucleotide designed to lower tau by targeting MAPT messenger RNA. Biogen said the study produced mean reductions of 50% to 65% in cerebrospinal fluid total tau across studied doses. The company also said diranersen reduced brain tau pathology measured by PET imaging, which the Alzheimer’s Association described as the first Phase 2 evidence that a drug treatment can remove toxic tau tangles from the brain in people living with early Alzheimer’s disease. (alz.org) ### Where does the “up to 65%” figure come from? The 50% to 65% figure refers to mean reductions in cerebrospinal fluid total tau, not a blanket cut in every tau measure. Biogen said those reductions were seen across all studied doses in CELIA. (investors.biogen.com) PET imaging was the separate brain-based measure. Biogen and outside investigators said the trial showed reductions in tau pathology on PET as well, but the summaries available publicly in the source material emphasized the existence of robust PET reductions rather than a single headline percentage for PET itself. (alz.org) ### Did patients also do better clinically? The 60 mg dose produced the strongest reported clinical effect in the company’s July 14 presentation. Biogen said that dose slowed decline by 26% on CDR-SB, 42% on ADAS-Cog13 and 50% on MMSE at 18 months. (investors.biogen.com) The Alzheimer’s Association said the trial showed slowing of clinical decline across multiple measures, with the most robust response at the lowest dose studied. Biogen’s earlier topline release in May also said prespecified analyses showed slowing across all studied doses, particularly in participants receiving 60 mg every 24 weeks. ### Was the trial a clean win? (investors.biogen.com) Biogen said on May 14 that CELIA did not meet its primary endpoint assessing dose response. The company nevertheless said the biomarker and efficacy data were strong enough to support registrational development. Professor Cath Mummery of University College London Hospitals said the results provide “some of the clearest evidence” that reducing tau pathology can translate into clinically meaningful benefit. (investors.biogen.com) Priya Singhal, Biogen’s head of development, said the company viewed the data as Phase 2 proof of concept for diranersen’s tau-directed mechanism. (alz.org) ### How should readers interpret this result right now? Diranersen is still experimental and is not approved by the U.S. Food and Drug Administration or other regulators, the Alzheimer’s Association said. The available results are from a Phase 2 study, which is designed to test signal, dose and safety rather than deliver final proof for routine clinical use. (investors.biogen.com) UCLH said the global CELIA study involved 416 people with early Alzheimer’s disease and that the treatment was generally well tolerated, with most adverse events reported as mild or moderate. The hospital also said more than 90% of participants who completed the placebo-controlled phase entered the long-term extension study. (investors.biogen.com) ### What happens next for diranersen? Biogen said after the July 14 presentation that it plans to advance diranersen into confirmatory Phase 3 development. UCLH said additional analyses from CELIA and the ongoing extension study will be presented at future scientific meetings as the program moves forward. (alz.org) The next concrete milestone is Phase 3 trial design and regulatory engagement. The Alzheimer’s Association also said its next Tau Global Conference is scheduled for June 2027 in Tokyo, where tau-focused research will remain a central topic. (alz.org) (investors.biogen.com) (uclh.nhs.uk)