Gosuranemab failed to meet its primary and key secondary goals in a Phase 2 study evaluating its use in treating progressive supranuclear palsy, an atypical parkinsonian disorder, its developer, Biogen, has announced.
Based on these results, Biogen will cease the clinical development of gosuranemab for this and other neurodegenerative diseases characterized by the buildup of toxic tau protein aggregates, collectively known as tauopathies.
“We are disappointed with the efficacy results of the Phase 2 PASSPORT study,” Alfred Sandrock, executive vice president of Research and Development and chief medical officer at Biogen, said in a press release.
“We remain unwavering in our commitment to advancing therapies that have the potential to address the significant unmet medical needs of people with neurodegenerative diseases,” he added.
Parkinson’s disease and progressive supranuclear palsy have similar disease manifestations, including slow movements and difficulties with gait. However, the hallmark of Parkinson’s is the toxic accumulation of misfolded forms of the alpha-synuclein protein within nerve cells, and tau for progressive supranuclear palsy.
Gosuranemab, previously known as BIIB092, aims to treat diseases where formation of toxic clumps (aggregates) of the tau protein occurs. This antibody is designed to bind to a specific part (N-terminal) of the tau protein, which would reduce the spread of the abnormal form of this molecule within nerve cells, potentially slowing disease progression.
Based on these findings, Biogen opened the placebo-controlled, safety and efficacy Phase 2 study (NCT03068468) of gosuranemab, called PASSPORT, in April 2017.
The study recruited 490 people with progressive supranuclear palsy, who were given 50 mg/ml of gosuranemab intravenously (into the vein) or a placebo once every four weeks for 48 weeks. All participants, including those in the placebo group, were then set to be treated with gosuranemab at 50 mg/ml once a month from week 52 up to week 208.
PASSPORT’s primary goal (endpoint) was to assess the therapy’s efficacy using the progressive supranuclear palsy rating scale (PSPRS), a 100-point scale that helps to measure disease progression.
But topline results from week 52 showed no statistically significant changes in PSP scale.
Key clinical secondary endpoints were also not met, including changes in the Unified Parkinson’s Disease Rating Scale Part II (which assesses motor experiences of daily living), the Clinical Global Impression of Change (measuring symptom severity), the Repeatable Battery for the Assessment of Neuropsychological Disease Severity (evaluating cognition), and the Progressive Supranuclear Palsy Quality of Life scale.
The treatment’s safety profile in the PASSPORT study was similar to that observed in previous studies.
Gosuranemab is continuing to be studied for Alzheimer’s, in the Phase 2 safety and tolerability TANGO trial (NCT03352557) in 654 people with mild Alzheimer’s disease with or without mild cognitive impairment.
Alzheimer’s is marked by the toxic aggregation of a protein called amyloid-beta.