Biogen announced today that its anti-tau passive immunotherapy, gosuranemab, had failed to pass muster in a Phase 2 trial for people with progressive supranuclear palsy. Biogen will continue testing the immunotherapy in the Phase 2 TANGO trial for Alzheimer’s disease, but will halt a basket trial of four other primary tauopathies: corticobasal syndrome, nonfluent variant primary progressive aphasia, frontotemporal dementia caused by tau mutations, and traumatic encephalopathy. This decision was based on differences in disease pathology, according to a company press release. Earlier this year, AbbVie had likewise decided to halt primary tauopathy trials yet continue an AD trial when its anti-tau immunotherapy, ABBV-8E12, failed a futility analysis in a PSP trial (Jul 2019 news).
- PSP trial missed primary and secondary endpoints.
- Phase 2 TANGO trial for AD is continuing.
- Biogen will not test the antibody in other primary tauopathies.
A humanized IgG4, gosuranemab, aka BIIB092, was originally developed by iPierian to neutralize extracellular N-terminal fragments of tau. The company hoped that the antibody would slow the spread of toxic fragments of tau through the brain. In animal models of frontotemporal dementia, the antibody did appear to neutralize tau toxicity (Nov 2012 news). Bristol-Myers Squibb acquired iPierian in 2014 and, in a Phase 1 trial, the antibody appeared safe. After Biogen licensed gosuranemab from BMS, in 2017 it ran a Phase 1b that suggested the antibody all but eliminated N-terminal tau fragments in cerebrospinal fluid. Biogen began recruiting for the Phase 2 trial in 2015.
PASSPORT, a 52-week trial, enrolled 490 patients who received either placebo or a 50 mg/ml intravenous infusion of gosuranemab every four weeks for 48 weeks. Change from baseline in the PSP rating scale at week 52 was the primary endpoint. There was no difference between treatment and placebo arms. The treatment made no dent in secondary endpoints, either, according to the press release. These included the Clinical Global Impression of Change, the Repeatable Battery for the Assessment of Neuropsychological Disease Severity, the PSP Quality of Life Scale, and a version of the Unified Parkinson’s Disease Rating Scale.
The Phase 2 TANGO trial began in May 2018. It is evaluating the antibody in 654 people who are amyloid-positive and have mild cognitive impairment or a diagnosis of mild AD. It is primarily a safety trial, with adverse events and serious adverse events at year 1.5 and up to 4.5 being the primary outcome. Change in the Clinical Dementia Rating-Sum of Boxes at 1.5 years will serve as an efficacy measure. It is expected to run until May 2021.
TauBasket, the primary tauopathy trial, began in September 2018 and was expected to run until April 2020. It, too, was primarily to assess safety, with a slew of biomarkers as secondary outcome measures, including volumetric and functional MRI, CSF total tau, phospho-tau, and neurofilament light chain, and functional and cognitive measures.—Tom Fagan
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