Lundbeck Advances Lu AF28996 in Parkinson’s Phase II

VALBY, Denmark, October 6, 2026

Phase Ib Study Shows Consistent Motor Improvements

The Phase Ib trial evaluated Lu AF28996, a novel oral prodrug of a D1-like/D2-like dopamine receptor agonist, in people with advanced Parkinson’s disease whose motor symptoms remained sub-optimally controlled despite optimized non-invasive antiparkinsonian medication. In Part B of the study, 34 participants received Lu AF28996 twice daily for six weeks, while 25 participants entered an optional extension period lasting up to an additional 12 weeks. Most treatment-emergent adverse events were considered mild, and no unexpected safety signals were observed. The most commonly reported adverse events included nausea, dizziness, and falls. The exploratory findings showed changes in several measures of daily motor control. At baseline, participants experienced an average of 9.5 hours of Good ON-time, 4.7 hours of OFF-time, and 1.8 hours of ON-time with troublesome dyskinesia each day. By Week 6, Good ON-time increased by 3.6 hours, while OFF-time decreased by 2.3 hours. At Week 18, Good ON-time remained increased by 3.4 hours from baseline, while OFF-time was reduced by 2.0 hours. ON-time with troublesome dyskinesia decreased by 1.2 hours at Week 6 and 1.4 hours at Week 18.

Lu AF28996 Advances Into Randomized Phase II Trial

Additional findings included reductions in dyskinesia severity measured using the Unified Dyskinesia Rating Scale (UDysRS). The total score decreased by 8.5 points at Week 6 and 14.5 points at Week 18 from a baseline score of 28.3. Mean daily levodopa dose also decreased, with reductions of 53.4% at Week 6 and 29.2% at Week 18. Among participants who had at least one hour of troublesome dyskinesia per day at baseline, daily ON-time with troublesome dyskinesia decreased by 2.3 hours at Week 6 and 2.8 hours at Week 18. Lundbeck has now initiated the DARE2 Phase II trial, a randomized, double-blind, parallel-group, placebo-controlled study designed to further evaluate Lu AF28996. The trial plans to enroll approximately 150 adults with Parkinson’s disease who continue to experience motor fluctuations despite optimized non-invasive symptomatic treatment. Its primary endpoint is the change from baseline to Week 19 in daily Good ON-time. The first participant has been randomized, with recruitment underway at selected sites in the United States and additional sites planned across Europe and Japan.

Investigational Therapy Targets Dopamine Signaling

Lu AF28996 is an investigational oral prodrug designed to act on D1-like and D2-like dopamine receptors and potentially enhance dopaminergic signaling in the striatum for a prolonged period. Lundbeck is investigating the therapy for its potential to address motor fluctuations and levodopa-induced dyskinesia in Parkinson’s disease. The company notes that Lu AF28996 is not approved by the FDA or any other regulatory agency, and its safety and efficacy have not yet been established. The Phase Ib findings provide an early clinical signal that will now be evaluated in the larger, controlled DARE2 study. Because the Phase Ib trial was exploratory, involved a limited number of participants, and did not include a placebo or active comparator, the results require confirmation in randomized clinical research. The transition into Phase II therefore represents an important next step in Lundbeck’s development program for advanced Parkinson’s disease and improved management of motor complications.

Source: Lundbeck press release