prasinezumab (RG7935) / Roche, Prothena - LARVOL DELTA

SUSTAINED EFFECT OF PRASINEZUMAB ON PARKINSON'S DISEASE MOTOR PROGRESSION IN THE OPEN-LABEL EXTENSION OF THE PASADENA TRIAL, 5-YEAR UPDATE (ADPD 2026) - "The effect of prasinezumab on slowing motor progression in PD as measured by clinicians and study participants is sustained for 5 years versus an external comparator."

Clinical • CNS Disorders • Movement Disorders • Parkinson's Disease

DIGITAL HEALTH TECHNOLOGY DETECTS GROUP DIFFERENCES IN PRACTICALLY-DEFINED OFF L-DOPA STATE: RESULTS OF PADOVA PH IIB STUDY OF PRASINEZUMAB (ADPD 2026) - P2 | "Post-hoc DHT analyses showed consistent trends favoring prasinezumab in digital data collected in the practically-defined OFF L-DOPA state, in line with the PASADENA ph2a Simple Sum digital finding and clinical PADOVA readout."

CNS Disorders • Movement Disorders • Parkinson's Disease

PRASINEZUMAB'S IMPACT ON NEUROMELANIN- AND IRON-SENSITIVE MRI BIOMARKERS IN PARKINSON'S DISEASE: FINDINGS FROM THE PADOVA PHASE IIB STUDY (ADPD 2026) - P2 | "Exploratory biomarker analysis of PADOVA suggests that prasinezumab is biologically active. This is supported by imaging biomarkers crucial to PD pathology, showing a slowing in the progressive loss of NM signal in SNpc and reduced iron accumulation in the putamen."

Biomarker • P2b data • CNS Disorders • Movement Disorders • Parkinson's Disease

THE EFFICACY AND SAFETY OF MONOCLONAL ANTIBODIES THAT TARGET ALPHA-SYNUCLEIN IN PARKINSON'S DISEASE: A SYSTEMATIC REVIEW (ADPD 2026) - "Results were synthesised narratively, and sensitivity analysis removing studies with high risks of bias was performed. After screening 1509 articles, 10 publications comprising a total of 13 studies were included, investigating Prasinezumab, Cinpanemab, Exidavnemab, and Lu-AF82422. Monoclonal antibodies that target alpha-synuclein in Parkinson's disease have a favourable safety profile, but their efficacy remains unclear. Future trials may benefit from including subjects at earlier disease stages, diagnosed using biomarkers or recognised preclinical features prior to the onset of clinical symptoms. Longer duration of future studies may increase sensitivity to delayed therapeutic effects."

Clinical • Review • CNS Disorders • Movement Disorders • Parkinson's Disease

PRASINEZUMAB IN EARLY-STAGE PARKINSON'S DISEASE: ADDITIONAL DATA FROM THE PADOVA STUDY (ADPD 2026) - P2 | "Although the primary endpoint of PADOVA was missed, the totality of evidence suggests a possible clinical benefit of prasinezumab in slowing down disease progression in early-stage PD on top of symptomatic medication. Effects observed during double-blind treatment appear to be sustained over an additional 6 months of open-label treatment. These results warrant further exploration in Phase III."

CNS Disorders • Movement Disorders • Parkinson's Disease

CAN WE PREVENT PARKINSON'S DISEASE? (ADPD 2026) - "Promising results come from the prasinezumab and buntanetap trials and other drugs are coming to reduce alfa syn toxicity but also for genetic forms and enzyme iperactivity. However today it is possible to reduce the risk of PD , increasing and encouraging physical exercise, curing pre-diabetes, reduce the exposition to pesticides and pollution, reduce the intake of ultra processed food."

CNS Disorders • Melanoma • Metabolic Disorders • Movement Disorders • Parkinson's Disease • Solid Tumor • Type 2 Diabetes Mellitus • Vascular Neurology

CROSSING MOLECULAR BOUNDARIES: AN IMMUNOTHERAPEUTIC SIMULTANEOUSLY TARGETING AMYLOID-Β, TAU, AND Α-SYNUCLEIN AMYLOID AGGREGATES (ADPD 2026) - "Lecanemab, Etalanetug, and Prasinezumab biosimilars served as benchmarks. Amyl-2 has nanomolar affinity for amyloid aggregates, inhibits aggregation across Aβ, Tau, and α-synuclein, and promotes robust phagocytic clearance of amyloid aggregates. Amyl-2 presents a strong potential to act as a disease-modifying therapeutic across amyloid-driven neurodegenerative diseases. Ongoing optimization to enhance binding affinities, improve brain permeability and mitigate amyloid-related imaging abnormalities (ARIA) strengthens the translational promise of this platform technology for AD, PD, and other amyloid-mediated diseases."

Alzheimer's Disease • CNS Disorders • Movement Disorders • Parkinson's Disease

MODELING PARKINSON'S DISEASE PROGRESSION TO QUANTIFY LONG-TERM TREATMENT EFFECTS VIA THE CONCEPT OF 'TIME SAVED' (ADPD 2026) - P2 | "Long-term treatment effects were evaluated by comparing 5 year data from the prasinezumab Open-Label Extension (OLE) with simulated trajectories based on PPMI data... The comparison of PASADENA OLE data with PPMI-based model predictions supports potential disease-modifying efficacy with an estimated two years of 'time saved' providing an intuitive measure of long-term benefit. It can be hypothesized that among the increased number of participants withdrawing in year 5 in the PPMI cohort, participants progressing more rapidly might have been overrepresented. This emphasizes the critical need to account for missing data when assessing long-term, model-based treatment effects."

CNS Disorders • Movement Disorders • Parkinson's Disease

Poster Presentation - Sustained Effect on Prasinezumab on Parkinson’s Disease Motor Progression in the Open-Label Extension of the PASADENA Trial, 5-Year Update (Businesswire) - "Prothena partners present data ...at AD/PD 2026....At Year 5, the combined PASADENA arm (delayed- and early-start groups) showed less disease progression compared to the PPMI cohort. This lower progression was observed across multiple measures."

P2 data • Parkinson's Disease

Oral Presentation - Prasinezumab in Early-Stage Parkinson’s Disease: Additional Data from the PADOVA Study (Businesswire) - "Prothena partners present data ...at AD/PD 2026....Longer term data from the PADOVA OLE study in early-stage PD showed a sustained effect of prasinezumab in slowing Parkinson’s progression on top of effective symptomatic therapies. The totality of the evidence suggests a possible clinical benefit of prasinezumab..."

P2b data • Parkinson's Disease

Poster Presentation - Prasinezumab’s Impact on Neuromelanin- and Iron-Sensitive MRI Biomarkers in Parkinson’s Disease: Findings from the PADOVA Phase IIb Study (Businesswire) - "Prothena partners present data ...at AD/PD 2026....Exploratory biomarker analysis of PADOVA suggests that prasinezumab is biologically active. This is supported by imaging biomarkers crucial to PD pathology, showing a slowing in the progressive loss of neuromelanin signal in substania nigra pars compacta and reduced iron accumulation in the putamen."

Biomarker • P2b data • Parkinson's Disease

Poster Presentation - Digital Health Technology Detects Group Differences in Practically-Defined OFF L-DOPA State: Results of PADOVA Phase IIb Study of Prasinezumab (Businesswire) - "Prothena partners present data ...at AD/PD 2026....Post-hoc Digital Health Technology analyses showed consistent trends favoring prasinezumab in digital data collected in the practically-defined OFF L-DOPA state, in line with the PASADENA Phase 2a Simple Sum digital finding and clinical PADOVA readout."

P2b data • Parkinson's Disease

PASADENA: A Study to Evaluate the Efficacy of Prasinezumab (RO7046015/PRX002) in Participants With Early Parkinson's Disease (clinicaltrials.gov) - P2 | N=300 | Recruiting | Sponsor: Hoffmann-La Roche | Active, not recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Movement Disorders • Parkinson's Disease

PASADENA: A Study to Evaluate the Efficacy of Prasinezumab (RO7046015/PRX002) in Participants With Early Parkinson's Disease (clinicaltrials.gov) - P2 | N=316 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Recruiting ➔ Active, not recruiting

Enrollment closed • CNS Disorders • Movement Disorders • Parkinson's Disease

PASADENA: A Study to Evaluate the Efficacy of Prasinezumab (RO7046015/PRX002) in Participants With Early Parkinson's Disease (clinicaltrials.gov) - P2 | N=300 | Recruiting | Sponsor: Hoffmann-La Roche | Not yet recruiting ➔ Recruiting

Enrollment open • Movement Disorders • Parkinson's Disease

PASADENA: A Study to Evaluate the Efficacy of Prasinezumab (RO7046015/PRX002) in Participants With Early Parkinson's Disease (clinicaltrials.gov) - P2 | N=316 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Sep 2026 ➔ Sep 2031

Trial completion date • CNS Disorders • Movement Disorders • Parkinson's Disease

PASADENA: A Study to Evaluate the Efficacy of Prasinezumab (RO7046015/PRX002) in Participants With Early Parkinson's Disease (clinicaltrials.gov) - P2 | N=300 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Jun 2021 ➔ Feb 2021

Trial completion date • Movement Disorders • Parkinson's Disease

PASADENA: A Study to Evaluate the Efficacy of Prasinezumab (RO7046015/PRX002) in Participants With Early Parkinson's Disease (clinicaltrials.gov) - P2 | N=316 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial primary completion date: Mar 2020 ➔ Dec 2019 | Recruiting ➔ Active, not recruiting

Enrollment closed • Trial primary completion date • CNS Disorders • Movement Disorders • Parkinson's Disease

PASADENA: A Study to Evaluate the Efficacy of Prasinezumab (RO7046015/PRX002) in Participants With Early Parkinson's Disease (clinicaltrials.gov) - P2 | N=300 | Recruiting | Sponsor: Hoffmann-La Roche | Trial primary completion date: Jul 2019 ➔ Mar 2020

Trial primary completion date • Movement Disorders • Parkinson's Disease

PASADENA: A Study to Evaluate the Efficacy of Prasinezumab (RO7046015/PRX002) in Participants With Early Parkinson's Disease (clinicaltrials.gov) - P2 | N=300 | Not yet recruiting | Sponsor: Hoffmann-La Roche

New P2 trial • CNS Disorders • Movement Disorders • Parkinson's Disease

PASADENA: A Study to Evaluate the Efficacy of Prasinezumab (RO7046015/PRX002) in Participants With Early Parkinson's Disease (clinicaltrials.gov) - P2 | N=316 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Apr 2026 ➔ Sep 2026

Trial completion date • CNS Disorders • Movement Disorders • Parkinson's Disease

PASADENA: A Study to Evaluate the Efficacy of Prasinezumab (RO7046015/PRX002) in Participants With Early Parkinson's Disease (clinicaltrials.gov) - P2 | N=316 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Feb 2021 ➔ Apr 2026

Trial completion date • CNS Disorders • Movement Disorders • Parkinson's Disease

2025 Business Highlights and Upcoming Milestones (Businesswire) - "Roche is evaluating prasinezumab in the ongoing Phase 3 PARAISO clinical trial in ~900 participants with early-stage Parkinson's disease; primary completion expected in 2029 (NCT07174310); Roche has stated that prasinezumab has peak sales potential greater than $3.5 billion (unadjusted) and could be the first disease-modifying treatment for a condition that affects 10 million people worldwide...Bristol Myers Squibb is conducting the Phase 2 TargetTau-1 clinical trial in approximately 310 patients with early Alzheimer’s disease; primary completion expected in 1H 2027 (NCT06268886)."

Sales • Trial primary completion date • Trial status • Alzheimer's Disease • Parkinson's Disease

α-synuclein monoclonal antibodies in Parkinson's disease: A failed promise or unmet potential? (PubMed, J Neurol Sci) - "Although there is strong preclinical evidence supporting the efficacy of mAb in PD, several limitations prevent this from translating into tangible clinical benefit. These limitations do not necessarily indicate a fundamental flaw in the therapeutic concept, but they do highlight the urgent need for future research to prioritize addressing these limitations."

IO biomarker • Journal • Review • Alzheimer's Disease • CNS Disorders • Movement Disorders • Parkinson's Disease

The challenges of experimental pharmacology in identifying novel treatments for Parkinson's disease. (PubMed, Curr Opin Neurobiol) - "The drugs discussed are buspirone, JM-010, befiradol, mesdopetam, foliglurax, dipraglurant, tavapadon, prasinezumab, cinpanemab, nilotinib, minzasolmin, exenatide, NLY01, liraglutide, lixisenatide, and semaglutide. For each molecule, we examine how previous preclinical studies succeeded or failed in predicting efficacy in clinical trials and discuss possible ways to optimize animal-model design and selection to maximize the probability of translational success."

Journal • Review • CNS Disorders • Movement Disorders • Parkinson's Disease