Abstract Details

Title Results from a Phase 1b Study of UCB0599, an Orally Available, Brain-penetrant Inhibitor of Alpha-synuclein (ASYN) Misfolding in People Living with Parkinson’s Disease (PD)

Topic Movement Disorders

Presentation(s) Movement Disorders Posters (7:00 AM-5:00 PM)

Poster/Presentation
Number 137

Objective Assess safety and tolerability of UCB0599, a brain-penetrant oral small molecule inhibitor of ASYN misfolding, in people living with PD.

Background ASYN misfolding is one of the best genetically and pre-clinically validated first steps in the cascade leading to dopaminergic neuron loss, the hallmark of PD. UCB0599 is under development to address an urgent need, slowing PD progression; with pre-clinical data showing inhibition of the earliest events in the PD pathological cascade.

Design/Methods Thirty-one people with PD (Hoehn-Yahr stage 1–3, aged 40–80 years) were enrolled and received two discrete doses of UCB0599 (n=21) or placebo (n=10) over four weeks.

Results

In people living with PD (mean age: 64.3 years), with multiple age-related comorbidities, treatment-emergent adverse events (TEAEs) were reported in 81.0% (n=17) and 70.0% (n=7) of the UCB0599 and placebo groups, respectively. The most frequently reported TEAEs were: headache (33.3%), post-lumbar puncture syndrome, decreased glomerular filtration rate, and hypotension (9.5% each) in the UCB0599 groups, and headache, decreased glomerular filtration rate, and syncope (20.0% each) in the placebo group. The majority of TEAEs were mild/moderate in intensity (UCB0599: 61.9%; placebo: 60.0%).

TEAEs of special interest were reported in two participants from one UCB0599 group: unspecified hypersensitivity and urticaria (not serious or severe in intensity). One serious adverse event was reported with placebo (syncope), and two with UCB0599 (kidney injury updated to chronic renal failure after drug washout and non-cardiac chest pain).

No consistent or clinically relevant treatment-related patterns were observed for laboratory, vital sign, or electrocardiogram findings. No UCB0599 dose effect was observed on frequency or intensity of adverse events.

Conclusions UCB0599 was generally well tolerated with no significant safety or tolerability concerns identified in a population of older individuals with PD with age-related comorbidity; supporting further investigation of UCB0599 for the potential to slow PD progression.

Authors/Disclosures
Johan W. Smit, PhD (UCB Biopharma Srl) PRESENTER	Joah Smit has received stock or an ownership interest from UCB Srl. Joah Smit has received personal compensation in the range of $100,000-$499,999 for serving as a director clinical pharmacology with UCB Srl.
	No disclosure on file
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Johannes R. Streffer, MD	Dr. Streffer has received personal compensation for serving as an employee of H. Lundbeck A/S. Dr. Streffer has or had stock in H. Lundbeck A/S.
	No disclosure on file

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Abstract Details