Therapeutics

Gosuranemab

Overview

Name: Gosuranemab
Synonyms: BIIB092, 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

Background

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-terminal fragments 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).

Findings

From December 2014 to April 2016, Bristol-Myers Squibb ran a single-center, single ascending-dose study in 65 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. According to published results, there were no serious or severe adverse events, and all participants completed the treatment  (Qureshi et al., 2018). Infusion caused a dose-dependent increase in blood and CSF BIIB092, and a 67 to 97 percent decrease in CSF unbound eTau after 4 weeks. Doses of 210 mg and higher led to sustained eTau reduction for up to 12 weeks.

In 2015, both EMA and FDA assigned orphan drug status to this biologic.

In September 2015, a multi-center, multiple ascending-dose phase 1b trial in the U.S. began evaluating BIIB092 in 48 patients with progressive supranuclear palsy (PSP). Participants received doses of up to 2,100 mg, infused once every four weeks for 12 weeks, and were assessed for safety, pharmacology and immunogenicity. The trial ran until October, 2016, and offered participants an 18-month open-label extension study, which will run until 2020. 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 29 days of treatment, and 91-97 percent after 85 days. CSF Total tau and phosphorylated tau were unchanged. Results were subsequently published (May 2019 news on Boxer et al., 2019).

In April 2017, Biogen started PASSPORT, a 52-week, 86-site efficacy study comparing 50 mg/ml BIIB092 to placebo in 490 people with PSP. This trial is to run through September, 2019. Primary outcomes include change on the PSP rating scale, which measures movement problems, and safety.

From May 2018 to summer 2019, TANGO, a 105-center global phase 2 trial in Alzheimer’s disease, enrolled 654 participants with mild cognitive impairment due to AD or mild AD, who have a positive amyloid PET scan. The trial did not require tau PET at screening. The trial will compare monthly infusions of 3 different doses of BIIB092 to placebo for roughly 1.5 years, followed by three years of extended dosing. The primary outcome is the number of adverse events; secondary outcomes include change on the CDR-SB after 1.5 years of treatment, and whether participants develop anti-BIIB092 antibodies. The placebo-controlled phase will run through 2021, with the long-term extension expected to end in 2024.

In September, 2018, investigators at the University of California, San Francisco, began a Phase 1b placebo-controlled trial of BIIB092 in four different primary tauopathies: corticobasal degeneration, frontotemporal lobar degeneration with MAPT mutations, traumatic encephalopathy, or non-fluent primary progressive aphasia. This trial will enroll eight participants with each condition, randomized 3:1 to drug:placebo, who will receive six monthly infusions. The primary outcome is safety, secondary outcomes include PK measures, exploratory MRI and CSF biomarkers, and cognitive and functional measures. The study will run through April 2020.

For all clinical trials, see clinicaltrials.gov.

Clinical Trial Timeline

  • Phase 2
  • Study completed / Planned end date
  • Planned end date unavailable
  • Study aborted
Sponsor Clinical Trial 2016 2017 2018 2019 2020 2021 2022 2023 2024 2025 2026 2027 2028 2029
Biogen NCT03352557
N=528

Last Updated: 31 Oct 2019

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References

News Citations

  1. In the Running: Trial Results from CTAD Conference
  2. Anti-Tau Antibody Looks Safe, Hits Target
  3. SfN: Tau Toxicity in the Limelight

Paper Citations

  1. . A randomized, single ascending dose study of intravenous BIIB092 in healthy participants. Alzheimers Dement (N Y). 2018;4:746-755. Epub 2018 Dec 17 PubMed.
  2. . Safety of the tau-directed monoclonal antibody BIIB092 in progressive supranuclear palsy: a randomised, placebo-controlled, multiple ascending dose phase 1b trial. Lancet Neurol. 2019 Jun;18(6):549-558. PubMed.
  3. . Human secreted tau increases amyloid-beta production. Neurobiol Aging. 2015 Feb;36(2):693-709. Epub 2014 Sep 16 PubMed.

External Citations

  1. clinicaltrials.gov
  2. company press release
  3. company press release

Further Reading

Papers

  1. . A new step towards targeting tau. Lancet Neurol. 2019 Jun;18(6):517-518. PubMed.