Testing D1 Receptor Modulator Glovadalen in Phase 2 Trial for Parkinson Disease: Milton Biagioni MD, CMD

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"We were initially very impressed by the safety profile. We have not seen any increase in dopaminergic-type adverse effects. That is a great advantage for new therapies being developed in this population. We had also seen almost double the patient-reported global impression of improvement in the 2 arms compared with placebo, which for us was very remarkable."

Glovadalen (UCB) is an oral dopamine D1 receptor positive allosteric modulator currently being investigated in clinical studies for the treatment of patients living with Parkinson disease (PD) who experience significant daily motor fluctuations. Previous research has suggested that the D1 receptor selectivity and allosteric mechanism of action of glovadalen may minimize receptor overstimulation and off-target signaling, potentially reducing adverse events (AEs) commonly seen with dopaminergic therapies. Findings from a previous phase 1 study of glovadalen (NCT04867642) showed that the agent demonstrated an acceptable safety and tolerability profile, supporting its further development.

Newly presented data from the phase 2 ATLANTIS study (NCT06055985) of glovadalen in showed that the therapy improved OFF time in patients with PD, without any notable worsening of dopamine-related treatment emergent AEs or dyskinesias.¹ Presented by lead author Milton Biagioni MD, CMD, at the 2025 International Congress of Parkinson’s Disease and Movement Disorders (MDS), held October 5-9, in Honolulu, Hawaii, a total of 207 participants were randomized 1:1:1 to receive low-dose glovadalen (n = 70), high-dose glovadalen (n = 67), or placebo (n = 70) as an adjunct to optimized standard-of-care therapy for 10 weeks.

Participants were aged 35 to 85 years with a PD diagnosis for at least 5 years, experienced significant daily motor fluctuations, and received oral levodopa combination therapy with or without oral adjunctive antiparkinsonian therapies. The primary end point was the change from baseline to Day 70 in the average number of hours of OFF time and secondary end points included safety, tolerability and pharmacokinetics. In an interview with NeurologyLive^® at MDS 2025, Biagioni, senior medical director of UCB's Translational Medicine Neuroscience and Gene Therapy, shared the latest findings from ATLANTIS and its potential implications for patients with PD.

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REFERENCES
1. Biagioni M, Nicholl R, Bornemann T, et al. Glovadalen, a D1 Receptor Positive Allosteric Modulator for People With Parkinson’s Who Experience Significant Daily Motor Fluctuations: A Phase II, Double-Blind, Randomized Trial. Presented at: 2025 MDS Congress; October 5-9; Honolulu, Hawaii. LBA-20.