Biogen has halted development of gosuranemab, the company’s first anti-tau antibody. The company announced as much in a June 16 release of top-line results of TANGO, a Phase 2 trial that evaluated the immunotherapy in people who had either mild cognitive impairment due to AD, or mild AD dementia. The treatment failed to slow cognitive decline on the clinical dementia rating-sum of boxes (CDR-SB), the trial’s primary efficacy endpoint. It also came up short on all exploratory cognitive measures.
- Phase 2 TANGO trial missed primary endpoint, i.e., slowing of cognitive decline.
- The immunotherapy lowered N-terminal tau fragments in CSF.
- No change in tau accumulation as measured by PET.
The results of the AD trial are the latest in a string of failures for gosuranemab, which also flopped in trials for the primary tauopathy progressive supranuclear palsy (Dec 2019 news). The antibody is trained to tau’s N-terminus, and joins other N-terminal antibodies, including Roche’s semorinemab, in showing no signs of efficacy. The field has since shifted focus to antibodies against tau’s midsection, which houses the aggregation-coaxing microtubule binding domains (Mar 2021 conference news).
TANGO enrolled 654 people who had evidence of amyloid accumulation. The participants, who ranged from 50 to 80 years of age, were randomized to receive monthly infusions of placebo or low, medium, or high doses of gosuranemab for 18 months.
The drug was safe and well-tolerated at all doses, but at 18 months had failed on the CDR-SB. None of the treatment groups benefitted on exploratory cognitive measures, either, slipping just as much as the placebo group on the Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS-Cog 13), the Alzheimer Disease Cooperative Study Activity of Daily Living (ADCS-ADL), the Mini-Mental State Examination (MMSE), and the Functional Assessment Questionnaire (FAQ).
Consistent with prior studies, gosuranemab did appear to engage its target, because N-terminal tau fragments dropped in the cerebrospinal fluid of those in the treatment groups. However, the antibody had no effect on tau accumulation as measured by tau-PET scans over 78 weeks.
Biogen terminated the trial, which was previously slated to include a long-term extension. The company also announced that it would discontinue clinical development of gosuranemab.—Jessica Shugart
- Gosuranemab, Biogen’s Anti-Tau Immunotherapy, Does Not Fly for PSP
- N-Terminal Tau Antibodies Fade, Mid-Domain Ones Push to the Fore