Biogen Successfully Targets Tau in Phase Ib Alzheimer's Study

Pictured: Dominic Walsh, Ph.D., VP Alzheimer's disease and dementia research unit, Biogen/company courtesy

Pictured: Dominic Walsh, Ph.D., VP Alzheimer's Disease and Dementia Research Unit, Biogen/company courtesy

With approvals for Aduhelm (aducanumab) and Leqembi (lecanemab) under its belt, Biogen presented data Wednesday for an Alzheimer’s disease therapy with a different target at the International Conference on Alzheimer’s and Parkinson’s Diseases (AD/PD 2023) in Stockholm, Sweden.

In a Phase Ib study, Biogen’s BIIB080 successfully reduced tau pathology in patients with early-stage AD, measured by PET scan, across all six brain regions analyzed.

“There wasn’t just a halt of progression,” Dominic Walsh, Ph.D., vice president of the Alzheimer's Disease and Dementia Research Unit at Biogen, told BioSpace. “There was a reversal.”

The investigational antisense oligonucleotide (ASO) therapy reduced biomarkers of tau in cerebrospinal fluid (CSF) across all dose groups. Baseline CSF tau levels were reduced by approximately 60% by the end of the long-term extension, Biogen reported.

BIIB080 is an intrathecal injection. It targets the messenger RNA associated with tau, which leads to reduced production of the protein. Participants received different dosing frequency in the Phase Ib study with cohorts at once per month and once per three months. Walsh said he hopes the dosing schedule can move to one dose per six months for patients’ convenience in Phase II.

Reducing the AD pathology related to tau is important because tau is more closely related to clinical and cognitive symptoms than AD’s other well-known biomarker, beta-amyloid, Laura Nisenbaum, executive director of drug development at the Alzheimer’s Drug Discovery Foundation, told BioSpace.

"It’s only when there is an increase in the tau pathology in the brain that you start to see symptoms. That’s why this is so encouraging.”

The location and amount of tau directly relates to symptom presentation and severity, Walsh said. Tau development in the frontal cortex manifests as impairment to executive function. Large tau deposits in the internal cortex and hippocampus result in patients struggling to encode and make new memories.

Biogen’s approved AD drugs, developed in collaboration with Eisai, are monoclonal antibodies that target amyloid. Leqembi received conditional approval from the FDA in January 2022 after reducing clinical decline by 27% in patients with mild cognitive impairment or dementia.

Nisenbaum said amyloid is just one piece of the puzzle. “We know we’re going to need combination therapy, from a precision medicine approach.”  

BIIB080 is currently being developed as a monotherapy, but Walsh said it has potential as a combination therapy with an anti-amyloid drug.

“I think of [beta-amyloid] as being the match that starts the fire, with tau being the actual trees that burn. And once the trees alight, they become self-propagating,” he said.

Eisai is also developing a tau antibody, which is currently in a Phase II/III study for dominantly inherited AD, with Leqembi as the base therapy.

While Walsh did not discuss Eisai’s program directly, he said Biogen has run anti-tau antibody programs in the past. Both have now been stopped, and he said a number of other companies have seen anti-tau antibody programs fail.

Tau is a tricky target because scientists still do not understand what form of tau mediates AD. Walsh said Biogen’s program takes an agnostic view, attempting to turn down all forms of tau.

Biogen is recruiting for a Phase II trial to confirm BIIB080’s safety, tolerability and efficacy in patients with mild and moderate AD. Walsh said the company will target a very similar patient population to its Aduhelm and Leqembi trials, leaning on the past “recipe of success.”

Biogen is targeting a Phase II completion date in December 2026.

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