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Gosuranemab Fails to Show Efficacy in Phase 2 Progressive Supranuclear Palsy Trial

clinical trial fails

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.

Different doses of the therapy were found safe in a previous Phase 1 study (NCT02658916) in progressive supranuclear palsy patients.

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.

The post Gosuranemab Fails to Show Efficacy in Phase 2 Progressive Supranuclear Palsy Trial appeared first on Parkinson’s News Today.

Biogen Presents Data on Potential Therapies for Parkinson’s and Progressive Supranuclear Palsy

Biogen

Biogen has presented data of its research programs evaluating potential treatments for Parkinson’s disease and progressive supranuclear palsy, an atypical parkinsonian disorder (APD).

The data were presented at the International Congress of Parkinson’s Disease and Movement Disorders (MDS), held Oct. 5-9, in Hong Kong, China.

Parkinson’s disease and progressive supranuclear palsy have overlapping symptoms, such as slowed movements and gait difficulty, which hinders accurate diagnosis. However, while the hallmark of Parkinson’s disease is the toxic accumulation of alpha-synuclein proteins, progressive supranuclear palsy is characterized by the build-up of tau proteins.

BIIB054, developed by Biogen as a potential therapy for Parkinson’s disease, is an antibody that binds to clumps of alpha-synuclein, preventing it from spreading.

A recent Phase 1 pilot study (NCT02459886) in healthy participants and participants with early Parkinson’s disease showed that a range of single doses of BIIB054 have favourable safety, tolerability, and pharmacokinetics profiles, supporting its further clinical development.

Pharmacokinetics refers to the compound’s absorption, bioavailability, distribution, metabolism, and excretion in the body.

This led to the design of a Phase 2 study (NCT03318523) called SPARKS, to evaluate the safety, pharmacokinetics, and potential effectiveness of three doses of BIIB054 in Parkinson’s patients. The study was presented in a scientific poster titled “Design and Status of the BIIB054 SPARK Trial.”

This multicenter, randomized, double-blind, placebo-controlled study is currently recruiting patients with early, untreated Parkinson’s at 90 international sites. The first patient was enrolled in January 2018, and enrollment is expected to continue through the end of the year.

In North America, the study is being developed in cooperation with the Parkinson Study Group.

Participants with will be randomized to receive monthly either one of three doses of BIIB054 (250 mg, 1,250 mg, or 3,500 mg) or a placebo, directly into the blood, for two years.

The primary objective is to evaluate BIIB054’s safety, while secondary goals include the assessment of BIIB054’s effects in dopamine-producing nerve cells — the most affected cells in Parkinson’s disease — and in clinical symptom burden.

Interim data of the ongoing Phase 1 clinical study (NCT02658916) evaluating the safety of three doses (150, 700 or 2100 mg) of BIIB092 — Biogen’s experimental therapy for the treatment of diseases with toxic aggregates of tau protein — in patients with progressive supranuclear palsy also were presented.

The poster, “Open-label extension (OLE) of a multiple ascending dose (MAD) study of BIIB092 in participants with PSP: Safety analysis,” showed that all three doses of BIIB092 were safe and well-tolerated.

Treatment-related side effects occurred in 11 (23%) patients — with no apparent association with dose —  and eight patients had 10 serious side effects, which researchers considered to be non-related to BIIB092 treatment.

This data supports further studies on the safety and effectiveness of BIIB092 in people with progressive supranuclear palsy.

Biogen also presented specific data of the ongoing five-year observational study called Parkinson’s Progression Markers Initiative (PPMI) study (NCT01141023). The poster was titled “Effect of PD medication on disease progression as measured by rate of change in MDS_UPDRS and DaT SBR in PPMI study.”

Because during clinical trials for new Parkinson’s therapies it is common for patients to start to take approved symptomatic Parkinson’s medications, researchers evaluated the effects of those treatments in disease progression. This knowledge may help to improve Parkinson’s clinical trials’ design.

Among the 423 participants who entered the study, up to 55% of them started Parkinson’s medications —  dopamine agonists, levodopa, or MAO-B inhibitors — by one year after entering, and up to 78% of them by three years after enrollment.

The results showed that patients had a higher rate of disease progression — assessed through MDS-UPDRS, the most widely used scale to assess Parkinson’s progression — before starting medication than after starting it. Also, patients who started levodopa had slightly more severe disease at study entry (before starting medication) than those who started other Parkinson’s medications.

“The data … are a testament to Biogen’s commitment to its goal of delivering innovative therapies for people living with complex, neurodegenerative conditions like PSP [progressive supranuclear palsy] and PD [Parkinson’s disease],” Kate Dawson, MD, vice president of Biogen’s late-stage clinical development, in a press release.

“We look forward to advancing the clinical development programs to help better understand these challenging conditions,” she added.

Five additional posters related to Parkinson’s disease and progressive supranuclear palsy were presented by Biogen during the congress.

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