FDA Action Update, October 2025: Clearance, Acceptance, and Extension

The FDA was busy in October 2025, making a number of decisions on potential new therapeutic agents, including accepting a new drug application, granting a fast track designation, giving a clearance, and extending a review period

With all the treatments that have progressed through the pipeline of clinical development, the NeurologyLive^® team has been hard at work covering all the agency movements to make sure you are up to date on the latest news in neurology. To give you a chance to catch up on any of the headlines you may have missed in August, we’ve compiled all the updates into 1 place. The coverage includes the latest FDA approvals, new designations, submissions, resubmissions, and clinical trial initiations and holds.

FDA Fast Tracks Anti-MTBR-Tau-Targeting Antibody BMS-986446 for Alzheimer Disease

At the beginning of the month, on October 1, 2025, the FDA granted fast track designation to Bristol Myers Squibb’s investigational anti-microtube binding region-tau (anti-MBTR-tau) antibody, BMS-986446, for the treatment of patients with early-stage Alzheimer disease (AD). The drug is currently being studied in a phase 2 trial, dubbed TargetTau-1, which tests efficacy, safety, and tolerability of multiple doses in those with early AD.¹

Anti-MTBR-tau antibodies like BMS-986446 are designed to target the MTBR of tau protein, a critical domain that drives tau aggregation into neurofibrillary tangles in AD. Unlike full-length tau, MTBR fragments are highly aggregation-prone and appear early in disease progression, making them an attractive therapeutic target.

In preclinical models, BMS-986446 had shown an ability to reduce tau uptake and spread, while protecting against behavioral deficits in AD brain tissue. The agent binds to the R1-R3 regions of tau’s microtube-binding domain to block its spread and uptake, while activating microglia via Fc receptor signaling to enhance tau clearance through phagocytosis.

"The FDA’s Fast Track Designation for BMS-986446 underscores the urgent need for innovative therapies for Alzheimer’s disease and recognizes the potential of this investigational anti-MTBR-tau antibody to meaningfully alter the trajectory of disease progression," Laura Gault, senior vice president and head of development, Neuroscience, at BMS, said in a statement.¹

FDA Clears Roche’s Elecsys pTau181 Test for Ruling Out Alzheimer-Related Amyloid Pathology

A couple of weeks later, on October 13, 2025, the FDA cleared Roche’s Elecsys ptau181 test, marking it the first blood-based biomarker test available for use in primary care settings to assist in AD assessment and diagnosis. Through this minimally invasive test, clinicians may better identify patients in early stages of cognitive decline who are unlikely to have AD-related amyloid pathology.²

The Elecsys pTau 181 test, which gained the European CE mark earlier this year, is intended for patients 55 years and older presenting with signs, symptoms, or complaints of cognitive decline. It remains the first and only In Vitro Diagnostic Regulation–certified blood test to help rule out AD-associated amyloid pathology.

"By bringing Alzheimer's blood-based biomarker testing into primary care, we can help patients and their clinicians get answers sooner to support them earlier in their journeys," Brad Moore, president and chief executive officer at Roche Diagnostics, said in a statement.² "This milestone reflects Roche’s leadership in diagnostics and our commitment to expanding access to innovative testing for patients and their clinicians."

FDA Delays Review Deadline for Hunter Syndrome Agent Tividenofusp Alfa

On the same day, on October 13, 2025, the FDA extended Denali Therapeutics' review period for the company’s biologics license application (BLA) for tividenofusp alfa, an investigational therapy for Hunter syndrome, a rare lysosomal storage disorder. The revised PDUFA date for the therapy, which aims to become the first approved treatment for Hunter syndrome, is now set for April 5, 2026.³

The agency’s decision to extend the review period comes after Denali submitted additional pharmacology data in response to a routine information request as part of the FDA’s standard evaluation process. Importantly, the agency did not request any new efficacy, safety, or biomarker data as part of this amendment.

Denali noted that the supplemental pharmacology information does not alter the original benefit-risk assessment or the overall clinical pharmacology conclusions supporting tividenofusp alfa’s application. The BLA submission, accepted in July, was through the accelerated approval pathway and was based on primarily data from a phase 1/2, open-label, single-arm study of 47 patients.

"We appreciate the FDA’s continued collaboration throughout the review process,” Ryan Watts, PhD, chief executive officer at Denali, said in a statement. "We continue to prepare for the potential approval and commercial launch of tividenofusp alfa. We feel the urgency to deliver for the MPS community, and we are committed to working together with regulators, physicians, and advocates to bring this important therapy to individuals and families living with Hunter syndrome."³

FDA Accepts New Drug Application for Tau PET Imaging Agent MK-6240 in Alzheimer Disease

At the end of the month, on October 28, 2025, the FDA accepted Lantheus’ new drug application (NDA) for MK-6240, a PET imaging agent designed to target aggregated tau protein in patients with suspected AD. The FDA has set a Prescription Drug User Fee Act date of August 13, 2026, for the imaging agent, which has received fast track designation and is being used in nearly 100 active clinical trials.⁴

MK-6240, considered a PET imaging tracer, may be used to visualize and quantify tau burden in vivo and help select patients based on tau pathology for targeted trials. In non-AD tau disorders, negative MK-6240 does not exclude tau pathology; rather, it may reflect mismatch between tracer specificity and tau confirmation. As anti-tau therapies continue to emerge in the coming years, the belief is that imaging agents like MK-6240 could serve as biomarkers for target engagement, disease progression, and treatment effect.

The NDA submission is backed by pivotal data from two phase 3 studies, both of which met their coprimary end points of sensitivity and specificity to detect tau neurofibrillary tangles (NFTs). Data from the studies, announced earlier this year, reinforced the potential of MK-6240 as a diagnostic tool for patients with AD.²

"We’re pleased the FDA has accepted our Fast Track application for MK-6240, highlighting the urgent need for innovative Alzheimer’s diagnostic tools and the potential of MK-6240 to meet that need by enabling direct visualization of tau pathology," Brian Markison, CEO at Lantheus, said in a statement.⁴ "With over 100 disease-modifying therapies in development, including about 30 targeting tau and 40 targeting beta amyloid, imaging plays a critical role in diagnosis and treatment selection. If approved, MK-6240 would complement beta-amyloid PET imaging and emerging blood-based diagnostics, helping guide treatment strategies for providers and patients.”

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REFERENCES
1. Bristol Myers Squibb’s Anti-MTBR-Tau-Targeting Antibody, BMS-986446, Granted Fast Track Designation by U.S. FDA for the Treatment of Alzheimer’s Disease. News release. October 1, 2025. Accessed November 7, 2025. https://news.bms.com/news/details/2025/Bristol-Myers-Squibbs-Anti-MTBR-Tau-Targeting-Antibody-BMS-986446-Granted-Fast-Track-Designation-by-U-S--FDA-for-the-Treatment-of-Alzheimers-Disease/default.aspx
2. Roche’s Elecsys® pTau181 becomes the only FDA-cleared blood test for use in primary care to rule out Alzheimer’s-related amyloid pathology. News release. Roche. October 13, 2025. Accessed November 7, 2025. https://diagnostics.roche.com/us/en/news-listing/2025/fda-cleared-ptau181-alzheimers-blood-test.html
3. Denali Therapeutics announces FDA review extension of BLA for tividenofusp alfa for the treatment of MPS II (Hunter syndrome). News release. Denali Therapeutics. October 13, 2025. Accessed November 7, 2025. https://www.globenewswire.com/news-release/2025/10/13/3165786/0/en/Denali-Therapeutics-Announces-FDA-Review-Extension-of-BLA-for-Tividenofusp-Alfa-for-the-Treatment-of-MPS-II-Hunter-Syndrome.html
4. Lantheus announces FDA acceptance of new drug application for MK-6240, a PET imaging agent targeting tau in Alzheimer’s disease. News release. Lantheus. October 28, 2025. AccessedNovember 7, 2025. https://www.globenewswire.com/news-release/2025/10/28/3175415/0/en/Lantheus-Announces-FDA-Acceptance-of-New-Drug-Application-for-MK-6240-a-PET-Imaging-Agent-Targeting-Tau-in-Alzheimer-s-Disease.html