• Results from an 18-week, open-label Phase Ib trial of investigational Lu AF28996 in people with advanced Parkinson's disease are being presented at MDS 2026
• The trial provided initial safety and tolerability data for Lu AF28996, with most treatment-emergent adverse events reported as mild
• Descriptive changes from baseline in motor fluctuations were observed with Lu AF28996, including increases in Good ON-time and reductions in OFF-time, alongside reductions in dyskinesia severity
• Phase II development of Lu AF28996 is underway, with the first patient randomized in the DARE2 trial¹

H. Lundbeck A/S (Lundbeck) announced results from an open-label Phase Ib trial evaluating Lu AF28996, a novel, investigational, oral prodrug of D1-like/D2-like dopamine receptor agonist, in people with advanced Parkinson's disease experiencing motor symptoms sub-optimally controlled despite optimized non-invasive antiparkinsonian medication. The results are being presented at the International Congress of Parkinson's Disease and Movement Disorders® (MDS) 2026 in Seoul, South Korea.

Parkinson's disease is characterized by the progressive degeneration of dopamine-producing neurons in the brain.² While levodopa remains the cornerstone of symptomatic treatment, many people experience difficult-to-manage motor complications as the disease progresses.^3,4 These include fluctuations between periods of good symptom control ("ON-time") and periods when symptoms return or worsen ("OFF-time"), and treatment-related dyskinesia (involuntary movements) despite optimized treatment.³ For people with advanced Parkinson's disease, many treatment options involve invasive procedures or continuous drug delivery, requiring patients to meet specific eligibility criteria.^4,5 There remains a need for effective, well-tolerated and non-invasive treatment approaches that can provide more consistent motor control.

"Many people with advanced Parkinson's disease continue to experience motor fluctuations and dyskinesia that can significantly affect daily life," said Tarek Samad, Executive Vice President and Head of Research & Development at Lundbeck. "We are encouraged by the Phase Ib results with Lu AF28996, including the improvements observed alongside substantial reductions in levodopa dose. With the DARE2 Phase II trial now underway, we are taking the next step in evaluating its potential in a larger, randomized and controlled study."

Phase Ib results
NCT04291859 comprised Part A once- and twice-daily ascending-dose cohorts and Part B twice-daily cohorts B1–B3. The MDS 2026 presentation and this release report results from Part B. In Part B of the trial, 34 participants received Lu AF28996 twice daily for six weeks.⁶ Eligible participants could continue in an optional extension period of up to 12 additional weeks, and 25 participants elected to enter the extension.

During the trial, most treatment-emergent adverse events were considered mild. No unexpected safety signals were observed, and the safety profile was consistent with a dopaminergic mechanism of action of Lu AF28996. The most common treatment-emergent adverse events were nausea, dizziness, and falls.

At baseline, participants experienced a mean of 9.5 hours of Good ON-time (ON-time without troublesome dyskinesia), 4.7 hours of OFF-time, and 1.8 hours of ON-time with troublesome dyskinesia per day. At Weeks 6 and 18, respectively, Good ON-time increased from baseline by 3.6 and 3.4 hours, OFF-time decreased by 2.3 and 2.0 hours, and ON-time with troublesome dyskinesia decreased by 1.2 and 1.4 hours.

These changes were accompanied by reductions from baseline in dyskinesia severity, as measured by the Unified Dyskinesia Rating Scale (UDysRS) total score, of 8.5 points at Week 6 and 14.5 points at Week 18, from a baseline score of 28.3 points. Reductions in mean daily levodopa dose were observed, with reductions of 53.4% at Week 6 and 29.2% at Week 18.

Among participants with ≥1 hour/day of troublesome dyskinesia at baseline, mean changes from baseline in daily ON-time with troublesome dyskinesia were −2.3 hours per day at Week 6 and −2.8 hours at Week 18.

The trial was exploratory, involved a limited number of participants and did not include a placebo or active comparator. The findings are to be further explored in the larger, randomized and controlled DARE2 trial.

The Phase II DARE2 trial
DARE2 (NCT07514858) is a Phase II randomized, double-blind, parallel-group, placebo-controlled, flexible-dose trial evaluating Lu AF28996 in approximately 150 adults with Parkinson's disease who continue to experience motor fluctuations despite optimized non-invasive symptomatic treatment.¹ The primary endpoint is change from baseline to Week 19 in daily Good ON-time.¹

The first participant in DARE2 has been randomized, and recruitment is underway at selected sites in the United States. Additional sites are planned in the United Kingdom, Spain, Italy, Germany, France, Poland, the Czech Republic, Sweden and Japan. Current site information is available on ClinicalTrials.gov.¹