Patients in Lundbeck’s 18-week Phase Ib trial of Lu AF28996 started with roughly 4.7 hours of daily OFF-time and gained back more than two of them. At week six, Good ON-time rose by 3.6 hours from a baseline of 9.5 hours, and that gain held at 3.4 hours through week 18, the full extent of the optional extension period. The numbers come from an open-label, uncontrolled cohort of 34 participants, so they carry real interpretive limits, but Lundbeck is presenting them at MDS 2026 in Seoul as the foundation for a Phase II program that has already enrolled its first patient.
The dyskinesia picture is the detail worth watching closely. Among participants who entered the trial with at least one hour per day of troublesome dyskinesia, ON-time with those involuntary movements fell by 2.3 hours at week six and 2.8 hours at week 18. The Unified Dyskinesia Rating Scale total score dropped 14.5 points by week 18 from a baseline of 28.3, a shift that would be clinically meaningful if it survives placebo-controlled testing. Levodopa dose also fell, by 53.4% at week six, though it partially rebounded to a 29.2% reduction at week 18, suggesting some dose titration was happening across the extension period. Lu AF28996 is an oral prodrug that activates both D1-like and D2-like dopamine receptors, a different receptor profile from AbbVie’s recently approved JUVMO (tavapadon), which is selective for D1/D5. Whether dual-receptor engagement translates into a practical advantage for patients who still need levodopa on board is a question DARE2 will need to answer.
That trial, NCT07514858, is a randomized, double-blind, placebo-controlled study targeting approximately 150 adults with Parkinson’s disease and persistent motor fluctuations on optimized non-invasive treatment. The primary endpoint is change from baseline to week 19 in daily Good ON-time, the same metric the Phase Ib data tracked. Sites are active in the United States, with additional countries including the UK, Germany, Japan, and several others planned. The bar for what constitutes a meaningful advance in this space is already set: subcutaneous apomorphine infusion is approved for motor fluctuations in advanced Parkinson’s disease, and patients with the most severe symptoms often end up on device-aided therapies.
The most common adverse events in the Phase Ib cohort were nausea, dizziness, and falls, consistent with dopaminergic activity, and most were rated mild. The Phase II readout will determine whether the motor benefits and that tolerability profile hold when measured against a placebo, and whether the levodopa dose reduction stabilizes rather than partially reverting.
Lu AF28996: the facts in one place
- Also written: Lu-AF28996
- Sponsor: H. Lundbeck A/S
- Mechanism: dual dopamine D1-like and D2-like receptor agonist; oral prodrug
- Indication studied: advanced Parkinson’s disease
- Phase: Phase II (DARE2 trial ongoing); Phase Ib completed
- Enrollment: 34 (Phase Ib completed); 150 (Phase II expected)
- Primary endpoint: Good ON-time without troublesome dyskinesia
- Headline result: 18-week open-label Phase Ib in 34 participants: clinically meaningful improvements in Good ON-time and OFF-time; patients gained more than two hours from baseline of approximately 4.7 hours daily OFF-time by week six; reductions in troublesome dyskinesia and levodopa dose; generally well-tolerated
- Registry identifier: NCT04291859
- Current status: Investigational; not approved by any regulatory authority; Phase II trial (DARE2) ongoing as of October 6, 2026
- Phase Ib trial registered: NCT04291859
- Phase Ib data presented at AD/PD 2026: March 16, 2026
- Phase Ib data and Phase II initiation announced: October 6, 2026
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
