Synonyms: gosuranemab, BMS-986168, IPN007
Therapy Type: Immunotherapy (passive) (timeline)
Target Type: Tau (timeline)
Condition(s): Progressive Supranuclear Palsy, Alzheimer's Disease
U.S. FDA Status: Progressive Supranuclear Palsy (Phase 2), Alzheimer's Disease (Phase 2)
Company: Biogen, Bristol-Myers Squibb
This is a humanized IgG4 monoclonal anti-tau antibody. In April 2014, Bristol-Myers Squibb acquired iPierian, a biotechnology company that had developed IPN007, an antibody against extracellular, N-terminally fragmented forms of tau (eTau) that were originally isolated from familial AD patient-derived pluripotent stem cells (company press release). The rationale for this therapeutic approach is that eTau is proposed to be involved in the spread of pathology in tauopathies, and the antibody reportedly neutralizes toxicity of eTau in mouse models of frontotemporal dementia (Nov 2012 news). Secreted forms of tau were reported to cause neuronal hyperactivity, which could, in turn, increase Aβ production, fueling a feed-forward cycle (Bright et al., 2015). In 2017, Biogen licensed this antibody (company press release).
From December 2014 to April 2016, Bristol-Myers Squibb ran a single-center, single ascending-dose study in 64 healthy volunteers in Texas and California. This first human trial assessed safety parameters for up to eight months after administration of a single infusion of BIIB092.
In 2015, both EMA and FDA assigned orphan drug status to this biologic.
In September 2015, a multi-center, multiple ascending-dose phase 1 trial in the U.S. began evaluating BMS-986168 in 48 patients with progressive supranuclear palsy (PSP). Participants received doses of up to 2,100 mg of BIIB092, infused once every four weeks for 12 weeks and were assessed for safety, pharmacology and immunogenicity. The trial was to run until summer 2017, and offer participants an 18-month open-label extension study, which will run until 2019. At 2017 CTAD, BIIB092 was presented as having been safe and well-tolerated in this trial (Dec 2017 conference news). The antibody showed a dose-dependent accumulation in serum and CSF. There was a marked reduction in CSF free eTau, which exceeded 90 percent for all doses. Reductions averaged 90-96 percent after 39 days of treatment, and 91-97 percent after 85 days.
In April 2017, Biogen started PASSPORT, a 52-week, 61-site efficacy study comparing 50 mg/ml BIIB092 to placebo in 396 people with PSP. This trial is to run through November 2019.
In November 2017, Biogen listed a phase 2 trial in Alzheimer’s disease. Starting in May 2018, this trial aims to enroll 528 participants with mild cognitive impairment due to AD or mild AD, who have a positive amyloid PET scan. The trial does not require tau PET at screening. The trial will compare monthly infusions of 3 different doses of BIIB092 to placebo. Primary outcomes are a range of safety parameters including 12-lead EEG; secondary outcomes include change from baseline on the CDR-SB and whether participants develop anti-BIIB092 antibodies. The trial will run through 2020.
For all clinical trials, see clinicaltrials.gov.
Clinical Trial Timeline
- Phase 2
- Study completed / Planned end date
- Planned end date unavailable
- Study aborted
Last Updated: 11 May 2018
- Bright J, Hussain S, Dang V, Wright S, Cooper B, Byun T, Ramos C, Singh A, Parry G, Stagliano N, Griswold-Prenner I. Human secreted tau increases amyloid-beta production. Neurobiol Aging. 2015 Feb;36(2):693-709. Epub 2014 Sep 16 PubMed.
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