Anti-Tau Agent Gosuranemab Fails to Show Efficacy in Phase 2 Alzheimer Study

Biogen’s investigational antibody against the N-terminus of tau failed to meet any of the efficacy or exploratory end points in individuals with mild cognitive impairment or mild Alzheimer disease.

Biogen has announced that its investigational anti-tau antibody gosuranemab, previously known as BIIB092, has failed to meet the primary efficacy end point in the phase 2 TANGO study (NCT03352557) in patients with mild cognitive impairment (MCI) due to Alzheimer disease (AD) or those with mild AD.1

The primary efficacy end point in the 78-week trial was the change from baseline at the end of the trial on the Clinical Dementia Rating Scale–Sum of Boxes (CDR-SB) in the treatment group compared to the placebo group. Additionally, no beneficial effect was demonstrated on any of the exploratory end points, including 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).

The anti-tau antibody was well-tolerated by the study participants, and safety outcomes were consistent with what has been shown previously in the clinical development of the agent. The overall primary end point of the study was safety.

“While we are disappointed by the results of the phase 2 study of gosuranemab, we know that the path to innovation is not a straight line, and that we always learn from each trial. We are investing in a broad neuroscience pipeline, including other tau approaches for Alzheimer’s disease,” Alfred Sandrock, Jr., MD, PhD, head, Research and Development, Biogen, said in a statment.1 “We extend our deepest gratitude to the participants, site staff and the broader Alzheimer’s disease community who contributed to the TANGO study.”

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Gosuranemab was designed to target against the N-terminus of tau. Data from TANGO displayed that target engagement was shown, as there was a lowering of N-terminal tau in cerebrospinal fluid (CSF) samples, consistent with what has been shown in prior studies. Although, no statistically significant treatment effect was observed on tau-positron emission tomography (PET) scans at week 78 for any of the dose groups assessed.

Overall, TANGO enrolled 654 participants at 97 sites, aged 50 to 80 years who displayed gradual and progressive change in memory function over a period of more than 6 months who also met all of the clinical criteria for MCI due to AD or mild AD. All participants had to have a CDR-SB score of 0.5 for MCI due to AD, or 0.5 or 1 for mild AD; a MMSE score of 22 to 30 (inclusive); a CDR Memory Box score of at least 0.5; and needed to demonstrate amyloid-positivity confirmed by CSF or amyloid-PET. The almost 700 individuals were randomized to receive intravenous low-, medium-, or high-dose gosuranemab or placebo once every 4 weeks.

This news marks the second such failure for Biogen’s anti-tau agent, after the late-2019 news that top-line results from the phase 2 PASSPORT study (NCT03068468) showed gosuranemab failed to meet the primary and secondary end points in patients with progressive supranuclear palsy (PSP), ultimately leading to discontinuation of the trial.2

PASSPORT was a double-blind, placebo-controlled, parallel-group study that included 490 participants randomly assigned to either 50-mg gosuranemab or placebo. Patients were administered treatment intravenously once every 4 weeks for 48 weeks in the double-blind treatment period, followed by dosing once every 4 weeks from weeks 52 to 208. Those included were assessed on change from baseline in the PSP Rating Scale (PSPRS) at week 52, and the investigators additionally measured the frequency of deaths, serious adverse events, adverse events leading to discontinuation, and grade 3 and 4 laboratory abnormalities to assess the safety and tolerability profile.

Gosuranemab’s failure in TANGO also follows a major success for Biogen in AD, after its anti-amyloid agent aducanumab (Aduhlem) was approved for the treatment of AD in early June 2021.3 This was the first approval in the AD space since 2003 and marked a major moment for the role of amyloid in the treatment of AD, with some suggesting that it might open the door for combination approaches with other pathology-targeting agents, such as those targeting tau, like gosuranemab.

REFERENCES
1. Biogen Announces Topline Results From Phase 2 Study of Gosuranemab, an Anti-Tau Antibody, for Alzheimer’s Disease. News release. Biogen. June 16, 2021. Accessed June 17, 2021. https://investors.biogen.com/news-releases/news-release-details/biogen-announces-topline-results-phase-2-study-gosuranemab-anti
2. Biogen reports top-line results from phase 2 study in progressive supranuclear palsy. News release. Biogen. December 13, 2019. Accessed June 17, 2021. https://www.globenewswire.com/news-release/2019/12/13/1960373/0/en/Biogen-Reports-Top-Line-Results-from-Phase-2-Study-in-Progressive-Supranuclear-Palsy.html
3. FDA’s Decision to Approve New Treatment for Alzheimer’s Disease. FDA. June 7, 20121. Accessed June 7, 2021. https://www.fda.gov/drugs/news-events-human-drugs/fdas-decision-approve-new-treatment-alzheimers-disease