Background

This is a humanized monoclonal antibody targeting α-synuclein originally developed by the Swedish company BioArctic. Genetic and pathology evidence implicate aggregated forms of α-synuclein in the molecular pathogenesis of Parkinson’s disease and other α-synucleinopathies such as dementia with Lewy bodies (DLB). In 2018, AbbVie licensed this and similar antibodies from BioArctic, and until 2022 developed it for the treatment of PD.

BioArctic engineered several antibodies that bind oligomeric/protofibrillar α-synuclein with nanomolar affinity and high selectivity over monomeric protein (Lindström et al, 2014; Kallab et al., 2018). Preclinical work with ABBV-0805 showed protection against α-synuclein toxicity, as well as clearance of pathological aggregates and prolonged survival in α-synuclein transgenic mice (Nordström et al., 2021). In the same mice, early and long-term treatment strongly reduced phosphorylated α-synuclein pathology, and transiently preserved memory behaviors, with no evidence of inflammatory response or toxic effects (Ekmark-Lewén et al., 2023).

ABBV-0805 is one of several α-synuclein antibodies being investigated for PD. Others include TAK-341, LU AF82422, and prasinezumab. Biogen’s cinpanemab was discontinued in 2021.

Findings

In March 2019, AbbVie began a Phase 1 study of ABBV-0805 in healthy volunteers in the United States (press release). Data presented at the September 2021 International Congress of Parkinson’s Disease and Movement Disorders reported pharmacokinetic, safety and tolerability data that warranted continuing into Phase 2, with once-monthly dosing. A second Phase 1 study was conducted. An intravenous and a subcutaneous formulation were evaluated in a total of 98 healthy Caucasian, Japanese, and Han Chinese volunteers. Results, including exploratory target engagement data, were published after peer review (Boström et al., 2024).

In March 2020, AbbVie started what was going to be a multicenter, placebo-controlled Phase 1 study in 32 people with idiopathic, mild to moderate Parkinson’s. It was going to randomize them to three escalating doses of antibody or placebo, delivered by intravenous infusion every 28 days, with a fourth dose being added pending initial results. Primary outcomes were going to be adverse events and antibody pharmacokinetics in blood and cerebrospinal fluid. In July 2020, the company withdrew this trial, citing strategic reasons.

On April 20 2022, BioArctic announced that AbbVie had terminated its collaboration on α-synuclein antibodies, including ABBV-0805 (press release).

In October 2024, BioArctic began a new Phase 2 trial. The placebo-controlled study plans to enroll 24 people with mild to moderate PD in two dose cohorts. Participants will receive multiple intravenous infusions over six months, against endpoints of adverse events, pharmacokinetics, and anti-drug antibodies. The study is running at five locations in Poland and Spain, with completion planned for March 2026.

On March 17, 2025, BioArctic announced that the U.S. FDA gave exidavnemab orphan drug designation for the synucleinopathy multiple systems atrophy (press release).

On May 8, 2025, the company announced that Poland and Spain had approved a protocol amendment to the Phase 2 trial, allowing the inclusion of 12 patients with multiple systems atrophy (press release).

For details on ABBV-0805 trials, see clinicaltrials.gov.