Date: 2015-06-17
Type of information: Presentation of results at a congress
phase: 1
Announcement: presentation of resultsat the 19th International Congress of Parkinson's Disease and Movement Disorders
Company: Prothena (Ireland) Roche (Switzerland)
Product: PRX002
Action
mechanism: monoclonal antibody. PRX002 is a monoclonal antibody targeting αα-synuclein, a major component of pathological inclusions that characterize several neurodegenerative disorders, including Parkinson\'s disease, dementia with Lewy bodies, and multiple system atrophy. PRX002 has been tested in various cellular and animal models of synuclein-related disease. Passive immunization with 9E4, the murine version of PRX002, in multiple transgenic mouse models of Parkinson\'s disease reduced the appearance of synuclein pathology, protected synaptic connections and improved performance by the mice in behavioral testing. PRX002 may slow or reduce the progressive neurodegeneration associated with synuclein misfolding and/or the cell-to-cell transmission of the pathogenic forms of synuclein.
Disease: Parkinson's Disease
Therapeutic area: Neurodegenerative diseases
Country: USA
Trial
details: This Phase 1 randomized, double-blind, placebo-controlled, multiple ascending dose study of PRX002 was initiated based upon safety and tolerability observed to date in the ongoing study in healthy volunteers, and is expected to enroll up to 60 patients with Parkinson\'s disease at multiple centers across the United States. The multiple ascending dose escalation trial is designed to evaluate the safety, tolerability, pharmacokinetics and immunogenicity of PRX002, and will also evaluate multiple clinical and exploratory biomarkers. Patients will be enrolled in escalating dose cohorts of PRX002 or placebo and will be observed for up to 6 months. (NCT02095171 - single ascending dose and NCT02157714 - multiple ascending dose).
Latest
news: * On June 17, 2015, Prothena Corporation, a late-stage clinical biotechnology company focused on the discovery, development and commercialization of novel protein immunotherapy programs, presented clinical results from a Phase 1 single ascending dose study of PRX002, a monoclonal antibody for the potential treatment of Parkinson's disease and other related synucleinopathies. Presented as part of the late breaking session at the 19th International Congress of Parkinson's Disease and Movement Disorders, the data demonstrated that PRX002 was safe and well-tolerated in healthy volunteers, meeting the primary objective of the study. Further, results from this study showed that administration of PRX002 led to a mean reduction of free serum alpha-synuclein levels of up to 96%. These overall results were highly statistically significant (p < 0.00001). Reduction of free serum alpha-synuclein, a protein potentially involved in the onset and progression of Parkinson's disease and the target of PRX002, was shown to be robust, rapid, and dose- and time-dependent after a single dose. The Phase 1 double-blind, placebo-controlled, single ascending dose study enrolled 40 healthy volunteers. All volunteers enrolled were randomized 3:1 into five escalating dose cohorts (0.3 mg/kg, 1 mg/kg, 3 mg/kg, 10 mg/kg or 30 mg/kg) to receive either PRX002 or placebo. No serious adverse events or hypersensitivity reactions were reported. PRX002 demonstrated favorable pharmacokinetic properties, supporting the current dosing frequency in the on-going Phase 1 multiple ascending dose study in patients with Parkinson's disease. Treatment-emergent adverse events in greater than 5% of subjects were vessel puncture site pain, headache, viral infection, nausea, neutropenia, upper respiratory infection and pruritus. All PRX002-related adverse events were mild and no dose limiting toxicities were observed. No anti-drug antibodies were detected. * On March 19, 2015, Prothena announced positive results from a Phase 1 single ascending dose study of PRX002. PRX002 was safe and well-tolerated, meeting the primary objective of the study. Further, results from this study showed that administration of PRX002 leads to mean reduction of free serum alpha-synuclein levels of up to 96%. These overall results were highly statistically significant (p<0.00001). Reduction of free serum alpha-synuclein, a protein potentially involved in the onset and progression of Parkinson's disease and the target of PRX002, was shown to be robust, rapid and dose-dependent after just a single dose. The Phase 1 double-blind, placebo-controlled, single ascending dose study enrolled 40 healthy volunteers. All volunteers enrolled were randomized 3:1 into five escalating dose cohorts (0.3 mg/kg, 1 mg/kg, 3 mg/kg, 10 mg/kg or 30 mg/kg) to receive either PRX002 or placebo. No hypersensitivity reactions or drug-related serious adverse events were reported. PRX002 demonstrated favorable pharmacokinetic properties, supporting the current dosing frequency in the on-going Phase 1 multiple ascending dose study in patients with Parkinson's disease. There were no treatment emergent adverse events (TEAEs) in greater than 10% of subjects. The only TEAEs in greater than 5% of subjects were vessel puncture site pain, headache and viral infection. All PRX002-related adverse events were mild and no dose limiting toxicities were observed. "We are extremely pleased with the results of the Phase 1 single ascending dose study as the mean reduction of free serum alpha-synuclein of up to 96% demonstrates the pharmacodynamic effects of PRX002," commented Gene Kinney, PhD, Chief Scientific Officer and Head of Research and Development at Prothena. "Importantly and for the first time in humans, we demonstrated that this robust, rapid and dose-dependent reduction of free serum alpha-synuclein was safe and well-tolerated. Thus, this approach may translate into a clinically meaningful delay or reversal of disease progression in patients with Parkinson's disease. We look forward to building upon these data with results from the on-going, multiple ascending dose study in patients with Parkinson's disease expected in the first half of 2016, where we will also be measuring levels of PRX002 in the cerebrospinal fluid and assessing additional biochemical, imaging and clinical biomarker endpoints." * On July 31, 2014, Prothena Corporation, a clinical stage biotechnology company focused on the discovery, development and commercialization of novel antibodies for the potential treatment of diseases that involve protein misfolding or cell adhesion, announced that the first patient with Parkinson\'s disease has been successfully dosed in a Phase 1 multiple ascending dose clinical trial of PRX002, a potential disease-modifying treatment for Parkinson\'s disease. This study builds upon an ongoing Phase 1 single ascending dose study initiated in April 2014 designed to evaluate PRX002 in healthy volunteers. As announced in December 2013, Prothena entered into a worldwide collaboration with Roche to develop and commercialize antibodies that target α-synuclein, including PRX002. To date, Prothena has received $45 million of the potential $600 million in total milestones through its collaboration with Roche.
