Therapy Type: Immunotherapy (passive) (timeline)
Target Type: alpha-synuclein
Condition(s): Parkinson's Disease
U.S. FDA Status: Parkinson's Disease (Phase 2)
Company: Biogen, Neurimmune
BIIB054 is a human-derived monoclonal antibody directed against α-synuclein. Genetic and pathology evidence implicate this protein in the molecular pathogenesis of Parkinson's disease (PD) and other α-synculeinopathies such as dementia with Lewy bodies (DLB). In 2010, Biogen licensed BIIB054 from Neurimmune (see company press release). No peer-reviewed data are published on this antibody. It was likely generated with the same reverse translational medicine technology from naturally occurring, presumably protective antibodies found in healthy aged donors as were aducanumab and other antibodies in the Biogen-Neurimmune partnership.
At conferences, BIIB045 has been reported to selectively bind aggregated over monomeric α-synuclein, to inhibit α-synuclein spreading in cell-based assays, and to slow pathology and motor symptoms in mice (May 2017, May 2018 conference news).
From July 2015 through 2017, Biogen evaluated single ascending, intravenous doses of BIIB054 in 48 healthy volunteers and 18 people with early Parkinson's, at eight sites in the U.S. Outcomes included safety measures, the MOCA cognition screen, BIIB054 serum levels and pharmacokinetics, as well as presence of anti-BIIB054 antibodies.
At the 2017 AD/PD conference, Biogen reported some data on the healthy volunteer cohort, aged 40 to 65. They had received infusions of 1, 5, 15, 45, 90, or 135 mg/kg, had MRI scans at baseline, day 3, and week 4, and had CSF samples drawn at baseline, 8 hours, 24 hours, and week 3. Participants were followed for 16 weeks after dosing with clinical assessments and electrocardiograms. Doses up to 90 mg/kg were reported to have been well tolerated; in the 135 mg/kg cohort, one participant developed asymptomatic ischemia in the right parietal lobe. Side effects included headache, dizziness, pain or skin rash related to the infusion. BIIB054’s half-life was 28 days, the CSF/serum ratio was 0.2 percent at all doses, and maximum concentration in blood was dose-proportional (see May 2017 conference news).
At the 2018 AAN conference, Biogen presented first results of the same trial's PD cohort. Thirteen men and 5 women, aged 47 to 75, had received a single infusion of either 0, 15, or 45 mg/kg of BIIB054. Nine were not on PD medication, 5 were on levodopa, 2 on rasagiline, 2 on both. The pharmacokinetics of BIIB054 in patients were similar to those in healthy volunteers, with a 33-day serum half-life, a three-fold higher plasma concentration in the high-dose versus low-dose group, and 0.4 and 0.3 percent reaching CSF in the high and low-dose groups, respectively. None of the patients developed anti-BIIB054 antibodies.
According to Biogen, BIIB054 formed plasma complexes with α-synuclein in both cohorts. Both doses formed similar amounts of complex, suggesting saturation of blood synuclein with antibody. BIIB054 is more selective for aggregated than soluble α-synuclein, but at high doses binds soluble protein, according to Biogen. No serious adverse events were reported (see May 2018 conference news).
In December 2017, Biogen started SPARK, a 2-year phase 2 trial in an estimated 311 people with PD. It will compare monthly infusions of 3 doses of BIIB054—250mg, 1250mg, or 3500mg—to placebo in order to evaluate safety, pharmacodynamic effects of the antibody on nigrostriatal dopaminergic nerve terminals, pharmacokinetics and immunogenicity of BIIB054. Primary outcome measures include adverse events, clinical labs, vital signs, neurological exam, as well as EKG and MRI. Secondary measures are I123 SPECT (DaTscan), BIIB054 serum concentration and percent of participants generating anti-BIIB054 serum antibodies. The trial is set to run until summer 2022, at 17 U.S. sites.
For all trials on this antibody, see clinicaltrials.gov.
Last Updated: 11 May 2018
- α-Synuclein Antibodies Enter Phase 2, Sans Biomarker
- New Alzheimer’s and Parkinson’s Immunotherapy Data at AAN
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