Biogen’s investigational therapy reduced tau protein levels in patients with Alzheimer’s

Key takeaways:

• Phase 1b trial of BII080 demonstrated dose-dependent and sustained reduction of tau protein in CSF, as well as reduction in aggregate tau pathology.
• Most adverse events were mild or moderate in severity.

Biogen Inc. has reported promising data from a phase 1b trial of BIIB080, an investigational antisense oligonucleotide therapy that reduced soluble tau protein in cerebrospinal fluid in patients with early Alzheimer’s disease.

According to a release from Biogen, the 25-week trial and open-label, long-term extension study evaluated the safety and tolerability of multiple dose levels of BIIB080 in 46 individuals with mild AD. Results showed the novel therapeutic reduced biomarkers of soluble tau in CSF (t-tau and p-tau181) in a dose-dependent and sustained manner, with all groups demonstrating a 60% reduction from baseline CSF tau levels by the end of the extension period.

In addition, BIIB080 reduced aggregated tau pathology, measured via positron emission tomography, in all brain composites, the release stated. Most adverse events were mild or moderate and included headache, back pain and post-lumbar puncture syndrome.

“To date, no tau-targeted investigational drugs have demonstrated an effect on tau PET, and the findings of the phase 1 trial suggest that directly targeting tau synthesis can have a substantial impact on pathologic tau,” Dominic Walsh, PhD, head of Biogen’s neurodegeneration research unit, told Healio in an email. “This is the first time that this magnitude of a reduction in pathologic tau has been observed in patients with Alzheimer’s disease in response to any therapeutic intervention.”

According to Biogen, tau protein can form “tangles” in patients with AD, which accumulate in brain regions responsible for cognition and promote damage and death to brain cells. The company has designed BIIB080 to target microtubule-associated protein tau mRNA and prevent production of tau protein.

“It is well established that the distribution and amount of aggregated tau correlates with the type and severity of symptoms seen in patients with AD and other tauopathies,” Walsh said. “This research, although early stage, is particularly exciting as it represents the first time this magnitude of a tau reduction has been observed in a clinical study. We believe BIIB080 has the potential to be a first-in-class therapy.”

Recruitment for the phase 2 CELIA study of BIIB080 is underway in the U.S., the release stated.