Lundbeck presents Phase Ib data for Lu AF28996 in advanced Parkinson’s disease, as Phase II trial begins

• 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

Valby, Denmark, Tuesday 6 October 2026 – H. Lundbeck A/S (Lundbeck) today 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

Lu AF28996 is not approved by the US Food and Drug Administration (FDA) or any other regulatory agency, and the efficacy and safety of Lu AF28996 have not been established.
 

About Parkinson’s disease
Parkinson’s disease (PD) is a progressive and disabling neurological disease characterized by motor symptoms including slowness of movement, tremor and rigidity, as well as a range of non-motor symptoms.^4,5 There are currently no established treatments that modify the progression of PD, and levodopa remains a cornerstone of symptomatic treatment.^2,4 With long-term levodopa treatment, many people develop motor complications, including periods when symptoms return or worsen (“OFF-time”) and dyskinesia (involuntary movements), which can significantly affect daily functioning and quality of life.^2-5

PD is the second most common neurodegenerative disease after Alzheimer’s disease and the most common movement disorder.^7,8 In 2021, an estimated 11.77 million people worldwide were living with PD, and its prevalence is projected to more than double by 2050.^8,9 As PD progresses, functional independence can decline and reliance on caregivers and healthcare systems can increase, contributing to a substantial personal, societal and economic burden.

About Lu AF28996
Lu AF28996 is an investigational, novel and oral prodrug of a D1-like/D2-like dopamine receptor agonist, with a pharmacologic profile that may enhance dopaminergic striatal signaling in a prolonged manner. It is being investigated for its potential to improve motor fluctuations and levodopa-induced dyskinesia in people with Parkinson’s disease. Concerted activation of D1- and D2-like dopamine receptors may play an important role in motor control.¹⁰

Lu AF28996 is not approved by the US Food and Drug Administration (FDA) or any other regulatory agency, and the efficacy and safety of Lu AF28996 have not been established.
 

About NCT04291859
NCT04291859 was an open-label Phase Ib trial evaluating the safety, tolerability and clinical effects of Lu AF28996 in people with advanced Parkinson’s disease experiencing motor fluctuations, with or without dyskinesia, despite non-invasive antiparkinsonian medication.

Thirty-four participants received Lu AF28996 twice daily for six weeks, followed by an optional extension period of up to 12 weeks. Twenty-five eligible participants elected to enter the extension period.

The trial was exploratory, involved a limited number of participants and did not include a placebo or active comparator. The findings require confirmation in larger, randomized and controlled clinical trials.
 

Contacts

About H. Lundbeck A/S
Lundbeck is a biopharmaceutical company focusing exclusively on brain health. With more than 70 years of experience in neuroscience, we are committed to improving the lives of people with neurological and psychiatric diseases.

Brain disorders affect a large part of the world’s population, and the effects are felt throughout society. With the rapidly improving understanding of the biology of the brain, we hold ourselves accountable for advancing brain health by curiously exploring new opportunities for treatments.

As a focused innovator, we strive for our research and development programs to tackle some of the most complex neurological challenges. We develop transformative medicines targeting people for whom there are few or no treatments available, expanding into neuro-specialty and neuro-rare from our strong legacy within psychiatry and neurology.

We are committed to fighting stigma and we act to improve health equity. We strive to create long term value for our shareholders by making a positive contribution to patients, their families and society as a whole.

Lundbeck has more than 5,000 employees in more than 20 countries and our products are available in more than 80 countries. For additional information, we encourage you to visit our corporate site www.lundbeck.com and connect with us via LinkedIn.

References:

1. https://clinicaltrials.gov/study/NCT07514858?term=nct07514858%20&viewType=Card&rank=1
2. Kalia LV, Lang AE. Parkinson's disease. Lancet 2015;386:896–912
3. Cenci MA. Front Neurol 2014;5:242
4. Stocchi F, et al. Nat Rev Neurol 2024;20:695–707
5. Heim B and Poewe W. J Parkinsons Dis 2025;16(2_suppl):24-37
6. Højer AM, et al. Poster presentation at International Congress of Parkinson’s Disease and Movement Disorders® (MDS) 2026
7. GBD. Global, regional, and national burden of neurological disorders during 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet Neurol 2017;16:877–897
8. Luo Y, et al. Front Aging Neurosci 2025;16:1498756
9. Su D et al. BMJ. 2025;388:e080952
10. Isaacson SH, et al. Clin Park Relat Disord. 2023;9:100212