Previewing Parkinson Disease Pipeline: Emerging Trials to Watch in 2026

In 2025, the NeurologyLive® team closely tracked key developments in Parkinson disease, including important trial readouts, regulatory updates, and expert guidance that directly informs clinical practice. Throughout the year, our focus has remained on delivering data-driven insights that matter to neurologists managing patients in real-world care settings.

Parkinson disease continues to evolve as an area of active investigation, with progress spanning symptomatic therapies, potential disease-modifying strategies, biomarker refinement, and earlier diagnostic approaches. While major headlines often draw immediate attention, many ongoing studies may have an equal or greater impact on long-term treatment decision making.

With a rapidly advancing research pipeline, it is challenging to narrow the field. Here, we highlight several of the most clinically meaningful ongoing Parkinson disease trials likely to influence care as we move into 2026.

1. LUMA Study of BIIB122/DNL151 (Biogen/Denali)

Luma, a phase 2 trial (NCT05348785) that began in 2022, tests the efficacy and safety of BIIB122, an investigational central nervous system-penetrant small molecule inhibitor of leucine-rich repeat kinase 2 (LRRK2), and whether they can slow the worsening of early-stage PD in adults between the ages of 30 and 80. This interventional trial features 650 participants across 113 trial sites and is expected to be completed by March 2026.

In the trial, patients are randomly assigned BIIB122 tablets or placebo, once a day, for a treatment period lasting between 48 and 144 weeks. Following their last dose, patients will also undergo a 2-week safety monitoring period for continued evaluation. Luma, which includes those with Modified Hoehn and Yahr scale stages 1 to 2, uses changes in Movement Disorders Society-Unified Parkinson’s Disease Scale (MDS-UPDRS) Parts II and III combined as the primary outcome over the 144-week period.¹

In June 2023, Biogen and Denali discontinued a portion of the clinical development program for BIIB122 known as the phase 3 LIGHTHOUSE study (NCT05418673), which was initiated in September 2022. The companies noted in the announcement that the decision was made “in consideration of the LIGHTHOUSE study’s complexity including the long timeline with anticipated study completion in 2031.” They added that the modifications were not because of safety or efficacy data from studies of the treatment and that they “remain committed to advancing the development of BIIB122.”²

2. ACTIVATE Trial of BIA 28-6156 (Bial) in GBA-PD

The phase 2 ACTIVATE study (NCT05819359) is a randomized, double-blind, placebo-controlled investigation of BIA 28-6156, a GCase enzyme-targeting therapy, in patients with PD who have a pathogenic variant in the glucocerebrosidase 1 (GBA1) gene (GBA-PD). Expected to conclude midway through 2026, the study uses change in MDS-UPDRS Part II and III score as the primary outcome measure, while looking at other measures such as Patient Global Impression scales, Modified Hoehn and Yahr score, and 39-Item Parkinson’s Disease Questionnaire (PDQ-39) score.³

The trial, expected to include 237 patients, consists of two parts: Part A, a genetic screening phase to identify individuals with PD-associated GBA1 variants, and Part B, the double-blind treatment phase. Eligible participants who meet inclusion criteria after a screening period of up to 5 weeks will be randomized 1:1:1 to receive BIA 28-6156 at either dose or placebo for up to 78 weeks, followed by a 30-day safety follow-up period.

There have been several phase 1 studies assessing the drug in single and multiple doses, ranging from 3 mg to 150 mg. So far, the drug has shown to be well-tolerated, with freqeutnyl reported treatment-emergent adverse events (TEAEs) like headache (BIA-28-6156: 15.2% vs. Placebo: 9.5%), back pain (6.1% vs. 3.2%), somnolence (5.3% vs. 4.8%), fatigue (4.9% vs. 9.5%) and myalgia (3.8% vs. 3.2%). In a previously presented post-hoc analysis of these trials, ranging across 327 patients, 52.0% of treated patients reported at least 1 TEAE, with SOC Nervous System Disorders as the most representative (BIA-28-6156: 23.5% vs. Placebo: 15.9%), followed by General disorders and administration site conditions (16.3% vs. 28.6%), and Musculoskeletal and connective tissue disorders (14.0% vs. 11.1%).⁴

3. Phase 1/2 Trial of Lithium in PD

A small-scale study (NCT06339034) featuring 20 early-stage patients with PD is currently testing the effects of lithium 20 mg/day compared with placebo on MRI and blood-based biomarkers. Expected to complete in the first half of 2026, the interventional trial features patients aged 40 to 80 who had a PD diagnosis for less than 4 years and have been on stable PD medications for at least 30 days without adjustments. In the trial, patients will receive a dietary supplement of lithium or placebo, using change in MRI-derived free water (FW) levels, peripheral blood mononuclear cell nuclear receptor-related 1 protein (Nurr1) mRNA expression, and changes in serum neurofilament light chain as primary outcomes.

Lithium, which was introduced in 1949, is a primary drug commonly used for the treatment of chronic mental illnesses, such as bipolar disorder, but is being studied in PD for its neuroprotective, disease-modifying, and protein-homeostasis effects. Among the reasons for its investigation, lithium is thought to inhibit glycogen synthase kinase-3ß, as well as increase the expression of neurotrophic factors such as BDNF and reduce pro-apoptotic signaling. Furthermore, lithium has been shown to stabilize mitochondrial function, reduce reactive oxygen species, and improve cellular resilience in experiemental models.

4. REGENERATE-PD Trial - AB-1005 (AskBio)

AB-1005 is an in investigational gene therapy for PD based on adeno-associated viral vector serotype 2 (AAV2) containing the human glial cell line-derived neurotrophic factor (GDNF) transgene. The agent, which showed promise in a phase 1 study, is currently being assessed in the phase 2 REGENERATE-PD trial (NCT06285643), an 87-patient cohort study with trial sites in Germany, Poland, the United Kingdom, and the United States. In this randomized, double-blind, surgery-controlled study, investigators will use change in normalized good ON time per Hauser Diary over an 18-month treatment period as the primary outcome.⁵

Currently, there are no FDA-approved therapies for PD that offer the same mechanism and target as AB-1005 does. Prior to REGENERATE-PD, the agent showed success in a previous phase 1b study (NCT04167540) in patients with PD, with results that showed successful putamen coverage and a safe profile over an 18-month period. Despite the fact that it was a small study of only 11 patients, neurosurgical delivery of AB-1005 led to putamen coverage of 63% (±2%), exceeding the goal of greater than 50% coverage.

In the mild cohort of the phase 1b study, PD symptoms remained relatively stable over 18 months, as measured by the MDS-UPDRS Part II, with similar stability observed on Part III. Patient-reported motor diaries showed a 1.3-hour reduction in good ON time, a 0.2-hour increase in ON time with troublesome dyskinesia, and a 1.1-hour increase in OFF time; however, one patient declined to complete the diary after dosing, and the company noted that increased dyskinesia and OFF time may have been influenced by a genetic defect of unknown pathological significance, potentially contributing to these changes over the study period.⁶

5. Phase 3 Extension Study – ABBV-951 (AbbVie)

In late 2024, the FDA approved AbbVie’s foscarbidopa/foslevodopa, marketed as Vyalev, as the first and only subcutaneous 24-hour infusion of levodopa-based therapy for the treatment of motor fluctuations in adults with advanced PD. The approval was supported by results from the phase 3 M15-736 study (NCT04380142), which evaluated continuous subcutaneous infusion of foscarbidopa/foslevodopa (ABBV-951) versus oral immediate-release carbidopa/levodopa in adults with advanced PD, along with findings from the 52-week open-label M15-741 study (NCT03781167) assessing long-term safety and efficacy.

Currently, there is an ongoing extension study (NCT04379050) of M15-741, expected to conclude around April 2026, that is continuing to evaluate the safety and tolerability of the therapy in adult patients with PD. The trial, anticipated to include 130 participants, will test outcomes like safety, vital signs, ECGs, MDS-UPDRS Parts I-IV, quality of life, and cognitive impairment, among others.⁷

6. TEMPO-4 Open-Label Study – Tavapadon (AbbVie)

The AHEAD 3-45 trial (NCT04468659) is a phase 3 study assessing the efficacy and safety of lecanemab in patients with preclinical AD and elevated amyloid and also in patients with early preclinical AD and intermediate amyloid. The aim of the study is to determine whether treatment with lecanemab is superior to placebo on change from baseline of the Preclinical Alzheimer Cognitive Composite 5 (PACC5) at 216 weeks of treatment and to determine whether treatment with lecanemab is superior to placebo in reducing brain amyloid accumulation as measured by amyloid PET at 216 weeks of treatment.

This study will also evaluate the long-term safety and tolerability of lecanemab in participants enrolled in the extension phase. Eligible participants were adults aged 55 to 80 years, with plasma biomarker results predictive of intermediate or elevated brain amyloid at screening or previously confirmed elevated or intermediate amyloid by PET, cerebrospinal fluid (CSF), or plasma testing. At screening, participants were required to have a global CDR score of 0, a MMSE score at least 27, and a Wechsler Memory Scale–Revised Logical Memory subscale II score at least 6.

7. Proof of Concept Study of Citalopram in PD

Citalopram is a selective serotonin reuptake inhibitor (SSRI) that is FDA-approved for the treatment of major depressive disorder and is widely used off-label for anxiety disorders. It works by increasing synaptic levels of serotonin (5-HT) in the brain through inhibition of the serotonin transporter. Currently, there is a proof-of-concept study (NCT04497168) testing whether citalopram can alter the build-up of toxic amyloid-beta plaques in the visuospatial cortex of the brain linked to visuospatial cognitive impairment in PD.

The phase 2 trial includes 58 patients testing the hypothesis that citalopram use in Parkinson disease will reduce visuospatial cortex Abeta plaque accrual, leading to an amelioration of longitudinal visuospatial cognitive decline linked to Parkinsonian dementia. In the study, patients aged 65 years and older without depression are randomly assigned to citalopram 20 mg daily or placebo for a 26-month period, using change in visuospatial cortex PiB distribution volume ratio as the primary outcome.⁹

REFERENCES
1. A Study to Learn About the Safety of BIIB122 Tablets and Whether They Can Slow the Worsening of Early-Stage Parkinson's Disease in Adults Between the Ages of 30 and 80 (LUMA). Cllinicaltrials.gov. Updated November 23, 2025. Accessed December 19, 2025. https://clinicaltrials.gov/study/NCT05348785
2. Statement: Biogen Provides Update on Parkinson’s Disease Clinical Development Program. News release. Biogen. June 5, 2023. Accessed January 2, 2025. https://investors.biogen.com/news-releases/news-release-details/statement-biogen-provides-update-parkinsons-disease-clinical
3. Efficacy, Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of BIA 28-6156 in GBA-PD (ACTIVATE). Clinicaltrials.gov. Updated December 10, 2025. Accessed January 2, 2025. https://clinicaltrials.gov/study/NCT05819359
4. Guedes L, Hilt D, Fonseca M, Peixoto I, Gama H. Integrated safety analysis of BIA-28-6156 phase 1 clinical trials (a novel allosteric activator of beta-glucocerebrosidase). Presented at 2023 MDS Congress. Abstract 59.
5. A Study of AAV2-GDNF in Adults With Moderate Parkinson's Disease (REGENERATE-PD) (REGENERATE-PD). Clinicaltrials.gov. Updated December 8, 2025. Accessed January 2, 2025. https://clinicaltrials.gov/study/NCT06285643
6. AskBio presents 18-month phase 1b trial results of AB-1005 gene therapy for patients with Parkinson disease. News release. AskBio. April 16, 2024. Accessed January 2, 2025. https://www.globenewswire.com/news-release/2024/04/16/2863581/0/en/AskBio-presents-18-month-Phase-Ib-trial-results-of-AB-1005-gene-therapy-for-patients-with-Parkinson-s-disease.html
7. Extension Study To Evaluate Safety And Tolerability Of 24-Hour Daily Exposure Of Continuous Subcutaneous Infusion of ABBV-951 In Adult Participants With Parkinson's Disease. Clinicaltrials.gov. Updated May 8, 2025. Accessed January 2, 2025. https://clinicaltrials.gov/study/NCT04379050
8. AbbVie Announces Positive Topline Results from Phase 3 TEMPO-1 Trial Evaluating Tavapadon as a Monotherapy for Parkinson's Disease. News release. September 26, 2024. Accessed January 2, 2025. https://news.abbvie.com/2024-09-26-AbbVie-Announces-Positive-Topline-Results-from-Phase-3-TEMPO-1-Trial-Evaluating-Tavapadon-as-a-Monotherapy-for-Parkinsons-Disease
9. Citalopram as a Posterior Cortical Protective Therapy in Parkinson Disease. Clinicaltrials.gov. Updated November 2, 2025. Accessed January 2, 2025. https://clinicaltrials.gov/study/NCT04497168