Lundbeck has reported results from an open‑label phase 1b trial evaluating Lu AF28996, an investigational 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 treatment. The findings are being presented at MDS 2026 in Seoul.
Parkinson’s disease involves progressive degeneration of dopamine‑producing neurons. Many people develop motor complications over time, including fluctuations between Good ON‑time and OFF‑time, and treatment‑related dyskinesia. Existing options for advanced disease often require invasive procedures or continuous drug delivery, highlighting the need for effective non‑invasive approaches.
Tarek Samad, Executive Vice President and Head of Research & Development at Lundbeck, said: “Many people with advanced Parkinson’s disease continue to experience motor fluctuations and dyskinesia that can significantly affect daily life. 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.”
In part B of the trial, 34 participants received Lu AF28996 twice daily for six weeks, with 25 continuing for an optional 12‑week extension. Most treatment‑emergent adverse events were mild, with no unexpected safety signals. The most common events were nausea, dizziness and fall.
At baseline, participants experienced a mean of 9.5 hours of Good ON‑time, 4.7 hours of OFF‑time and 1.8 hours of ON‑time with troublesome dyskinesia. At Weeks 6 and 18, Good ON‑time increased 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. Dyskinesia severity, measured by UDysRS, improved by 8.5 points at Week 6 and 14.5 points at Week 18. Mean daily levodopa dose fell by 53.4% at Week 6 and 29.2% at Week 18.
Among participants with at least one hour per day of troublesome dyskinesia at baseline, ON‑time with troublesome dyskinesia decreased by 2.3 hours at Week 6 and 2.8 hours at Week 18. The exploratory trial involved a limited number of participants and no placebo or active comparator.
DARE2, a phase 2 randomised, double‑blind, placebo‑controlled trial, is now underway and will evaluate Lu AF28996 in approximately 150 adults. The primary endpoint is change from baseline to Week 19 in daily Good ON‑time. Recruitment has begun in the US, with additional sites planned across Europe and Japan.
Lu AF28996 is not approved by the FDA or any other regulatory agency, and its efficacy and safety have not been established.
