Gosuranemab Fails TANGO Trial; Biogen Stops Development

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by Patricia Inacio PhD |

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Gosuranemab

Gosuranemab, an investigational antibody against the tau protein, failed to meet its primary and exploratory efficacy goals in the TANGO Phase 2 study, its developer, Biogen, has announced.

Now, the TANGO trial has been terminated and Biogen will cease the clinical development of gosuranemab as a potential therapy for Alzheimer’s disease patients, the company said.

“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,” said Alfred Sandrock, Jr., MD, PhD, head of research and development at Biogen.

“We extend our deepest gratitude to the participants, site staff and the broader Alzheimer’s disease community who contributed to the TANGO study,” he added.

While the 1.5-year trial was unsuccessful, it did generate large amounts of data on the tau protein, which will aid in other studies, according to the pharmaceutical company.

“We are investing in a broad neuroscience pipeline, including other tau approaches for Alzheimer’s disease,” Sandrock said.

Gosuranemab, previously known as BIIB092, was designed for diseases characterized by the build-up of toxic clumps (aggregates) of the tau protein. The antibody binds to a specific domain in the tau protein, called the N-terminal, which would reduce the spread of the abnormal form of this molecule within nerve cells, potentially slowing disease progression.

In previous studies, gosuranemab was shown to bind to its target in the cerebrospinal fluid, which is the liquid that surrounds the brain and spinal cord. They, in turn, comprise the central nervous system, or CNS.

An international Phase 2 study (NCT03352557), TANGO had recruited 654 adults, ranging in age from 50 to 80, with mild Alzheimer’s or mild cognitive impairment (MCI) due to the disease. All of the participants had progressive impairment in memory function for more than six months.

Each patient was randomly assigned to receive three intravenous (into-the-vein) doses — a low, medium, or high dose — of either gosuranemab or a placebo, administered once every four weeks, or about once a month.

The study’s primary objective was to evaluate the safety and tolerability of gosuranemab. Its secondary goals, meanwhile, included the efficacy of multiple doses of the investigational therapy in slowing cognitive and functional impairment, as evaluated by changes in the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) scores.

Gosuranemab’s immunogenicity — its capacity to elicit an immune response — after multiple doses also was evaluated.

Topline results from week 78 showed that all three doses of gosuranemab failed to induce changes on CDR-SB scores as compared with the placebo. The results from week 78 — the last week of the study — had been compared with measurements from the trial’s start, or baseline.

Also, no benefits were seen in exploratory efficacy endpoints, 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).

There were no statistically significant changes in tau protein clumps for any dose groups, as observed using positron emission tomography (PET) imaging scans.

Safety data showed that gosuranemab was well-tolerated, and its safety profile was in agreement with previous studies.

Gosuranemab also had failed to show efficacy in the PASSPORT Phase 2 study (NCT03068468) in 2019. That trial involved participants with progressive supranuclear palsy, an atypical form of Parkinson’s disease, which also is characterized by the accumulation of tau aggregates.

Biogen said it plans to present additional results from the TANGO trial, including its data on CSF biomarkers, at future medical meetings.