Biogen is firing up a registrational programme for its tau-focused Alzheimer’s disease therapy, diranersen, despite the drug missing its primary endpoint in a mid-stage study.
During the ongoing Phase II CELIA trial (NCT05399888), which is exploring the efficacy and safety of the first-in-class antisense oligonucleotide (ASO) in patients with mild cognitive impairment from Alzheimer’s disease, diranersen failed to prompt a significant dose response for change in patient Clinical Dementia Rating–Sum of Boxes (CDR-SB) scores after 76 weeks.
However, Citi analysts noted that this endpoint miss “does not invalidate” the programme, while analysts from William Blair did not deem meeting the primary endpoint as a “requisite for advancing development”.
According to a pre-specified analysis of cognitive endpoints, all doses of the anti-tau evaluated did slow clinical decline – an impact that Biogen claims was particularly prevalent in patients taking the lowest 60mg dose given every 24 weeks.
Positron emission tomography (PET) scans also revealed that diranersen reduced the prevalence of tau in the cerebrospinal fluid and diminished tau pathology, with these impacts maintained across the dosing period.
Diranersen’s safety and tolerability in this Phase II trial mirrored the drug’s profile in the Phase Ib study. While the incidence of adverse events (AEs) was comparable across all the dose cohorts, there was a higher prevalence of serious AEs in the highest dose studied.
Though Biogen is yet to share specific data on the Phase II results, the company says it will present findings at the 2026 Alzheimer’s Association International Conference (AAIC).
In response to the preliminary data, William Blair analysts noted they are “cautiously optimistic to see that slowing of cognitive decline was observed across all studied doses and in the lowest dose where benefit was highest.”
Targeting tau in Alzheimer’s
Biogen acquired diranersen, otherwise known as BIIB080, through an exclusive license deal with the drug’s creator and co-developer, Ionis Pharmaceuticals, back in 2019. Ionis designed diranersen to diminish the production and abnormal intra- and extracellular accumulation of tau, a protein that facilitates the movement of nutrients along axons in a healthy brain.
According to Biogen, tau accumulation is a “hallmark” of Alzheimer’s disease that’s intimately linked with cognitive decline and neurodegeneration – meaning preventing accumulation in the brain could hold the potential to slow cognitive decline in patients.
In a statement, Biogen’s executive VP and head of development, Priya Singhal, touted the therapy’s potential, noting that the pharma believes diranersen has achieved “an unprecedented and compelling confluence of efficacy and biomarker results”.
However, some are cautious on the commercial potential of a tau-based approach for this purpose, as William Blair analysts note that anti-amyloid therapies have “largely underperformed commercial expectations with similar profiles, albeit with significant risk that may be avoided” with anti-tau therapies".
While Philippa Salter, managing neurology analyst at GlobalData, said the results were “disappointing”, she did point out that Biogen’s confidence in the biomarker data around tau pathology and the slowing of cognitive decline is a silver lining.
“It is crucial that a larger Phase III study shows positive, clinically meaningful results to provide confidence in the benefit of targeting tau. Biogen must also prove they have learned from their experience developing Aduhelm (aducanumab), which flopped on launch following approval from biomarker data only,” Salter added.
Now, the field is looking ahead to the AAIC 2026 readout, which will help paint a clearer picture of diranersen’s potential efficacy and safety in early Alzheimer’s disease.
