prasinezumab (RG7935) / Roche, Prothena - LARVOL DELTA

PROGRESSION OF REMOTELY SMARTPHONE-COLLECTED VOICE IMPAIRMENTS IN EARLY PARKINSON'S DISEASE: EXPLORATORY RESULTS FROM THE PASADENA STUDY OF PRASINEZUMAB (ADPD 2025) - P2 | "No other significant negative or positive effects were observed. Conclusions These Results support frequent and remote collection of smartphone voice data to quantify hypokinetic dysarthria progression in early PD, both before and after start of dopaminergic treatment."

CNS Disorders • Movement Disorders • Parkinson's Disease

HOW THE THERAPEUTIC APPROACH TO EARLY PARKINSON'S DISEASE WILL CHANGE IN THE NEXT FUTURE (ADPD 2025) - "Levodopa remains the most efficacious drug, a better preparation of levodopa like IPX 203 can ensure more stable plasma levels of Levodopa...Tavapadon is a new dopamine agonist stimulating D1-D5 receptors which concluded the phase III. Other compounds such as CVN424 (Cerevance) orally active and selective GPR6 inverse agonist, piperamat (IRLAB 752) a cortical enhancer to improve balance, Clenbuterol/Nadolol for cognition, mesdopetam a D3 antagonist are under investigation...These include the monoclonal antibody prasinezumab, UCB0599 and buntanetap small-molecules α-synuclein aggregation inhibitor, the vaccine ACI-7104.056 by AC immune...The LRKK2 kinase inhibitor BIIB122/DNL151 is in phase IIb in PD. BIAL BIA 28-6156 activator of the GCase enzyme is under investigation in patients with GBA mutation. The combination of symptomatic and disease modifying therapy, the use of accurate biomarkers and more precise treatment will be the future in the treatment of PD."

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

Other activities at the AD/PD 2025 International Conference (Businesswire) - P2b | N=586 | PADOVA (NCT04777331) | Sponsor: Hoffmann-La Roche | "Although the study missed its primary endpoint, the totality of data suggest possible benefit in early-stage Parkinson’s disease. Prasinezumab showed potential clinical efficacy in the primary endpoint of time to confirmed motor progression with a hazard ratio (HR)=0.84 [0.69-1.01] and p=0.0657, missing statistical significance. In a pre-specified analysis, the effect of prasinezumab was more pronounced in the population treated with levodopa (75% of participants), HR=0.79 [0.63-0.99]. Consistent positive trends across multiple secondary and exploratory clinical endpoints were also observed, in addition to a potential biological effect of prasinezumab on MRI biomarkers."

P2b data • Parkinson's Disease

TWO-YEAR PROGRESSION OF WALKING AND TURNING IN DAILY LIFE OF EARLY PARKINSON'S DISEASE PARTICIPANTS: EXPLORATORY FINDINGS FROM THE PRASINEZUMAB PASADENA STUDY (ADPD 2025) - P2 | "Over 104 weeks, 8 features progressed in the delayed-start group, 6 of which progressed numerically less in the early-start prasinezumab group [Table 3]. Conclusions Exploratory PM measures of motor behavior during daily life appear reliable and valid biomarkers of disease severity and progression in early-stage PD, both before and after start of dopaminergic treatment."

IO biomarker • CNS Disorders • Movement Disorders • Parkinson's Disease • PD-1

METHODOLOGICAL CONSIDERATIONS SUPPORTING A TIME-TO-EVENT PRIMARY ENDPOINT IN THE PADOVA STUDY IN EARLY-STAGE PARKINSON'S DISEASE PARTICIPANTS ON STABLE SYMPTOMATIC TREATMENT (ADPD 2025) - P2 | "Methods The Phase IIb, multicentre, randomised, double-blind, placebo-controlled, parallel-group PADOVA study (NCT04777331) was designed to evaluate the efficacy, safety and pharmacokinetics of intravenous prasinezumab 1500 mg administered every 4 weeks in participants with early-stage PD who were on stable symptomatic monotherapy with either a monoamine oxidase type B inhibitor or levodopa for ≥3 months prior to randomisation...Results Full methodological details of the TTE approach used in the PADOVA study and additional sensitivity and prespecified subgroup analyses will be presented. Conclusions Insights from the PADOVA Phase IIb provide important evidence to support validation of the use of a TTE approach in early-stage PD for future clinical trials."

CNS Disorders • Movement Disorders • Parkinson's Disease

PADOVA: TOPLINE RESULTS FROM A PHASE IIB STUDY OF PRASINEZUMAB IN EARLY-STAGE PARKINSON'S DISEASE PARTICIPANTS ON STABLE SYMPTOMATIC TREATMENT (ADPD 2025) - P2 | "Topline efficacy and safety Results from the PADOVA study will be reported. Conclusions This is the first time that Results from PADOVA will be reported, and these will include important learnings for the design and conduct of future clinical development trials in early-stage PD."

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

Prasinezumab slows motor progression in Parkinsons disease: beyond the clinical data. (PubMed, NPJ Parkinsons Dis) - "Caution is needed due to the retrospective nature of subgroup analyses, and potential confounding factors that may have influenced the observed treatment effects in specific patient subsets. Critical considerations are provided here for designing and implementing preclinical studies and clinical trials involving monoclonal antibodies, suggesting that future research should prioritize refining preclinical models and optimizing biomarker-based patient selection to reduce risks of false trial outcomes, eventually advancing antibody-based therapies in PD effectively and safely."

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

Prasinezumab: A Bayesian Perspective on Its Efficacy. (PubMed, Mov Disord) - No abstract available

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

A Phase 2b, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of intravenous prasinezumab in early-stage Parkinson's disease (PADOVA): Rationale, design, and baseline data. (PubMed, Parkinsonism Relat Disord) - P2 | "PADOVA has successfully recruited an early-stage PD population to test the effect of prasinezumab when added to background SOC."

Clinical • Journal • P2b data • CNS Disorders • Movement Disorders • Parkinson's Disease

An update on immune-based alpha-synuclein trials in Parkinson's disease. (PubMed, J Neurol) - "Specifically, UB-312, AFFITOPE PD01A, PD03A and ACI-7104.056 are designed to provoke an immune response against α-syn (active immunisation), while Prasinezumab and Cinpanemab, MEDI1341 and Lu AF82422 focus on directly targeting α-syn aggregates (passive immunisation). Despite some promising results, challenges such as variable efficacy and trial discontinuations persist. Future research must address these challenges to advance disease-modifying therapies for PD around this therapeutic target."

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

Roche’s Phase IIb study of prasinezumab missed primary endpoint, but suggests possible benefit in early-stage Parkinson’s disease (Roche Press Release) - P2b | N=586 | PADOVA (NCT04777331) | Sponsor: Hoffmann-La Roche | "Prasinezumab showed potential clinical efficacy in the primary endpoint of time to confirmed motor progression with a HR=0.84 [0.69-1.01] and p=0.0657, missing statistical significance. In a pre-specified analysis, the effect of prasinezumab was more pronounced in the population treated with levodopa (75% of participants), HR=0.79 [0.63-0.99]. Consistent positive trends across multiple secondary and exploratory endpoints were also observed. Prasinezumab continues to be well tolerated and no new safety signals were observed in the study."

P2b data • CNS Disorders • Parkinson's Disease

Prothena Reports Third Quarter 2024 Financial Results and Business Highlights (Businesswire) - "'From our wholly-owned programs we expect to complete our confirmatory Phase 3 AFFIRM-AL clinical trial evaluating birtamimab, which is being conducted under a SPA agreement with the FDA at a significance level of 0.10, in 1H 2025. We also expect to announce multiple clinical readouts from our ongoing Phase 1 ASCENT clinical trials evaluating PRX012 for Alzheimer’s disease starting in mid-2025 and continuing throughout the year. In collaboration with Roche, we expect results from the Phase 2b PADOVA clinical trial evaluating prasinezumab for Parkinson’s disease in 4Q 2024 and with Novo Nordisk, we expect results from the Phase 2 signal-detection clinical trial evaluating coramitug for ATTR amyloidosis with cardiomyopathy in 1H 2025.'"

P1 data • P2 data • P2b data • Trial completion • Alzheimer's Disease • Amyloidosis • CNS Disorders • Metabolic Disorders • Parkinson's Disease

Sustained effect of prasinezumab on Parkinson's disease motor progression in the open-label extension of the PASADENA trial. (PubMed, Nat Med) - P2 | "PASADENA ClinicalTrials.gov no. NCT03100149 ."

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

Ntx101, an antibody to nitrated alpha synuclein, prevents spread of parkinson’s disease pathology in multiple pre-clinical models (Neuroscience 2024) - "Blinded IHC comparison of various mouse brain regions for NTX101 vs. 9E4, the murine parental antibody of prasinezumab, and/or mouse isotype control was assessed for relative efficacy in preventing pathology spread...These consistent results in different mouse models are strong confirmation of nSyn’s role as a pathogenic subspecies driving aggregate spread in the brain; thus, blocking nSyn represents an attractive therapeutic approach against PD. Towards this end, we have recently named a development candidate, NDC-0524, that targets nSyn and are advancing IND-enabling studies."

Preclinical • CNS Disorders • Parkinson's Disease

A Study to Evaluate the Efficacy and Safety of Intravenous Prasinezumab in Participants with Early Parkinson’s Disease (PADOVA): Rationale, Design, and Baseline Data (MDS Congress 2024) - "The PADOVA study population is suitable for investigating the potential of prasinezumab to slow disease progression in individuals with early PD on stable symptomatic therapy."

Clinical • CNS Disorders • Parkinson's Disease

Effect of Prasinezumab on Parkinson's Disease Motor Progression in a Long-term Open-label Extension of the PASADENA Trial (MDS Congress 2024) - "This exploratory analysis, which requires confirmation in further studies, suggests that prasinezumab might slow motor progression long-term in PD."

Clinical • CNS Disorders • Parkinson's Disease

Limitations and potential strategies of immune checkpoint blockade in age-related neurodegenerative disorders. (PubMed, J Physiol Sci) - "Lately, disease-modifying therapies (DMTs) that can alter the pathophysiology that underlies AD with anti-Aβ monoclonal antibodies (MAbs) (e.g., aducanumab, lecanemab, gantenerumab, donanemab, solanezumab, crenezumab, tilavonemab). Similarly, in Parkinson's disease (PD), DMTs utilizing anti-αSyn (MAbs) (e.g., prasinezumab, cinpanemab,) are progressively being developed and evaluated in clinical trials. These therapies are based on the hypothesis that both AD and PD may involve systemic impairments in cell-dependent clearance mechanisms of amyloid-beta (Aβ) and alpha-synuclein (αSyn), respectively, meaning the body's overall inability to effectively remove Aβ and αSyn due to malfunctioning cellular mechanisms. In this review we will provide possible evidence behind the use of immunotherapy with MAbs in AD and PD and highlight the recent clinical development landscape of anti-Aβ (MAbs) and anti-αSyn (MAbs) from these clinical trials in order to better investigate..."

Checkpoint block • Checkpoint inhibition • Journal • Review • Alzheimer's Disease • CNS Disorders • Dementia • Inflammation • Movement Disorders • Parkinson's Disease

Investigating the Mechanisms of Antibody Binding to Alpha-Synuclein for the Treatment of Parkinson's Disease. (PubMed, Mol Pharm) - "Monoclonal antibodies (mAbs) are biological drugs with high specificity, and Prasinezumab (PRX002) is an mAb currently in Phase II, which targets the C-terminus (AA 118-126) of α-syn...The mAb's developability was determined using computational screening methods. Our results demonstrate the efficiency and developability of this therapeutic agent."

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

Prothena Reports First Quarter 2024 Financial Results and Business Highlights (Businesswire) - "Topline results from Phase 2b PADOVA clinical trial in patients with early Parkinson’s disease, which has completed enrollment, expected in 2H 2024 (NCT04777331)...PRX019, a potential treatment of neurodegenerative diseases with an undisclosed target...Phase 1 clinical trial timeline update expected in 2024..."

Enrollment closed • New P1 trial • P2b data • CNS Disorders • Parkinson's Disease

Prasinezumab slows motor progression in rapidly progressing early-stage Parkinson's disease. (PubMed, Nat Med) - "This exploratory analysis suggests that, in a trial of 1-year duration, prasinezumab might reduce motor progression to a greater extent in individuals with more rapidly progressing Parkinson's disease. However, because this was a post hoc analysis, additional randomized clinical trials are needed to validate these findings."

Clinical • Journal • Behavior Disorders • CNS Disorders • Mental Retardation • Movement Disorders • Parkinson's Disease • Psychiatry • REM Sleep Behavior Disorder

Exploratory Analysis of PASADENA Open-label Extension Evaluating the Effect of Prasinezumab on the Progression of Motor Signs and Symptoms (AAN 2024) - "Progression in the PASADENA OLE population was relatively small compared to the RWD-PPMI cohort, suggesting that prasinezumab slowed the progression of motor signs and symptoms of PD. These exploratory results need to be confirmed in a randomized controlled trial."

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

Investigating the mechanisms of antibody binding with alpha-synuclein for the treatment of Parkinson's Disease | Poster Board #820 (ACS-Sp 2024) - "Monoclonal antibodies (mAbs) are biological drugs with high specificity, and Prasinezumab (PRX002) is a mAb currently in Phase II, which targets the C-terminus (AA 118-126) of α-syn...The mAb's developability was determined with computational screening methods. Our results demonstrate the efficiency and developability of this therapeutic agent."

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

SLOWER PROGRESSION OF DIGITAL ACOUSTIC SPEECH MEASURES IN EARLY PARKINSON'S DISEASE UNDER PRASINEZUMAB DURING THE FIRST 52 WEEKS OF THE PASADENA STUDY (ADPD 2024) - P2 | "These preliminary findings suggest that prasinezumab might have a beneficial effect on acoustic properties of speech, which may not be captured by single MDS-UPDRS items. Further work is warranted to evaluate meaningful changes in digital speech features with and without pharmacological intervention. These results support the feasibility of digital measures to track progression of Parkinson's Disease in clinical trials in a sensitive and ecologically valid manner, providing unique insights into the progression of the disease and efficacy of interventions."

CNS Disorders • Movement Disorders • Parkinson's Disease

A STUDY TO EVALUATE THE EFFICACY AND SAFETY OF INTRAVENOUS PRASINEZUMAB IN PARTICIPANTS WITH EARLY PARKINSON'S DISEASE (PADOVA): RATIONALE, DESIGN, AND BASELINE DATA (ADPD 2024) - P2 | "The study has successfully completed enrollment. The PADOVA study population is suitable for investigating the potential of prasinezumab to slow disease progression in individuals with early PD on stable symptomatic therapy. Trial Registration: NCT04777331."

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

PASADENA LONG-TERM OPEN-LABEL EXTENSION CONTINUE TO SHOW REDUCED MOTOR AND FUNCTIONAL PROGRESSION IN PRASINEZUMAB-TREATED INDIVIDUALS WITH EARLY-STAGE PARKINSON'S DISEASE COMPARED TO A REAL-WORLD DATA ARM (ADPD 2024) - "Disease worsening was less severe in the PASADENA OLE compared to the RWD-PPMI cohort, suggesting that prasinezumab might be effective in slowing the motor and functional progression of PD. These exploratory results require confirmation in a randomized controlled trial."

Clinical • Real-world • Real-world evidence • CNS Disorders • Movement Disorders • Parkinson's Disease