prasinezumab (RG7935) / Roche, Prothena - LARVOL DELTA

PARAISO: A Study to Evaluate the Efficacy and Safety of Intravenous (IV) Prasinezumab in Participants With Early-Stage Parkinson's Disease (clinicaltrials.gov) - P3 | N=900 | Recruiting | Sponsor: Hoffmann-La Roche | Not yet recruiting ➔ Recruiting

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

Updates on Active Clinical Development Portfolio: Prasinezumab (Businesswire) - "Partner Roche to initiate the Phase 3 PARAISO clinical trial evaluating prasinezumab for early-stage Parkinson's disease by the end of 2025 (NCT07174310)."

Trial status • Parkinson's Disease

Immunotherapy in Early Parkinson's Disease: A Biomarker-Driven Trial Framework for Secondary Prevention. (PubMed, Cureus) - "Although primary efficacy endpoints have not yet been achieved overall, prasinezumab has indicated exploratory slowing in faster progressors and digital measures. MEDI1341 has demonstrated Phase 1 target engagement with acceptable safety, and Lu AF82422 has shown Phase 1 target engagement, along with promising subgroup trends in MSA, and scheduled Phase 3. Meanwhile, cinpanemab was negative...We emphasize biomarkers that verify α-synuclein pathology during the asymptomatic phase and argue for a secondary-prevention model that treats the underlying biology before symptoms to maximize disease-modifying potential. We also propose a practical, biomarker-guided trial blueprint for secondary prevention, with explicit screening funnels and endpoint hierarchies."

Biomarker • IO biomarker • Journal • Review • 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 (MDS Congress 2025) - P2 | "Even though the primary endpoint of PADOVA was missed, results suggest a possible clinical benefit of prasinezumab in slowing down disease progression in early-stage PD on top of efficacious symptomatic medication. These results warrant further exploration and will inform future clinical trials."

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

Methodological considerations supporting a time-to-event primary endpoint in the PADOVA study in early-stage Parkinson's disease participants on stable symptomatic treatment (MDS Congress 2025) - P2 | " The Phase IIb PADOVA study (NCT04777331) evaluated the efficacy, safety and pharmacokinetics of prasinezumab in participants with early-stage PD on stable monoamine oxidase type B inhibitor or levodopa monotherapy for ≥3 months prior to randomization... Insights from the PADOVA study provide important evidence to support validation of the use of a TTE approach in early-stage PD for future clinical trials. This methodology can capture the benefits of new treatments in a reasonable timeframe and allows for precise and meaningful measurement of treatment effect."

CNS Disorders • Movement Disorders • Parkinson's Disease

PRASINEZUMAB: A BAYESIAN PERSPECTIVE ON ITS EFFICACY (WCN 2025) - "No substantial difference in efficacy was observed between subpopulations with or without rapid progression, agreeing with the results of the phase-two PASADENA trial, which did not reach the Primary End Point at 52 weeks. The exploratory analysis using the Bayes Factor did not support the supposed disease-modifying effect of prasinezumab."

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

PARAISO: A Study to Evaluate the Efficacy and Safety of Intravenous (IV) Prasinezumab in Participants With Early-Stage Parkinson's Disease (clinicaltrials.gov) - P3 | N=900 | Not yet recruiting | Sponsor: Hoffmann-La Roche

New P3 trial • CNS Disorders • Movement Disorders • Parkinson's Disease

Second Quarter, Recent Business Highlights and Upcoming Milestones (Businesswire) - "Partner Roche to advance prasinezumab into Phase 3 development for early-stage Parkinson's disease with initiation expected by the end of 2025...Roche has stated that prasinezumab has peak sales potential greater than $3 billion (unadjusted) and could be the first disease-modifying treatment for a condition that affects 10 million people worldwide...Prothena expects initial data in August from the Phase 1 ASCENT clinical trials....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 2027 (NCT06268886); Bristol Myers Squibb is also conducting a Phase 1 open-label single-dose clinical trial to assess a subcutaneous administration; primary completion expected in 2H 2025 (NCT06955741)."

New P3 trial • P1 data • Sales • Trial primary completion date • Alzheimer's Disease • 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

PreCoDe: Prevent Cognitive Decline in GBA-associated Parkinson's Disease (clinicaltrials.gov) - P2 | N=120 | Not yet recruiting | Sponsor: University Hospital Tuebingen

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

Time-to-event analysis mitigates the impact of symptomatic therapy on therapeutic benefit in Parkinson's disease trials. (PubMed, NPJ Parkinsons Dis) - "While the TTE approach yielded consistent hazard ratios between censored and non-censored analyses, the estimated difference between treatment arms using the change-from-baseline approach was lower without censoring than with censoring, suggesting a potential masking of prasinezumab treatment effects by symptomatic therapy. Thus, the TTE approach may mitigate the potential confounding effect of symptomatic therapy on MDS-UPDRS Part III."

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

Comparative assessment of binding and functional differences of clinical antibodies targeting α-synuclein in cellular models of Parkinson's disease. (PubMed, Biomed Pharmacother) - "Except cinpanemab, which binds the N-terminus of α-syn, all other clinical α-syn antibodies bind C-terminal epitopes...Our evaluation shows the impact of epitope, affinity, selectivity, and assay format on PFF uptake, and PFF-seed induced aggregation and S129 phosphorylation of endogenous α-syn in cellular models of PD. The comparative assessment provides new insights into the properties of α-syn antibodies and should aid in the design of next generation therapeutics for the treatment of PD and other synucleinopathies."

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

Exploratory digital outcome measures of motor sign progression in Parkinson's disease patients treated with prasinezumab. (PubMed, NPJ Digit Med) - P2 | "DHT sensor-based outcome measures may contribute to quantifying disease progression in clinical research of early-stage, dopaminergic treatment-naïve PD. Clinical Trial Registry Name: ClinicalTrials.gov; Clinical Trial Registry ID: NCT03100149; registered 2017-03-29."

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

Roche to advance prasinezumab into Phase III development for early-stage Parkinson’s disease (GlobeNewswire) - "Roche...announced today its decision to proceed with Phase III development of prasinezumab, an investigational anti-alpha-synuclein antibody, in early-stage Parkinson’s disease. This decision is informed by data from the Phase IIb PADOVA study and ongoing open-label extensions (OLEs) of PADOVA and Phase II PASADENA studies."

New P3 trial • Parkinson's Disease

Prothena Reports First Quarter 2025 Financial Results and Business Highlights (Businesswire) - "PRX012: Prothena expects to report multiple clinical readouts starting around mid-2025 and continuing throughout the year from the ongoing Phase 1 ASCENT clinical trials. Prothena has currently enrolled approximately 260 patients in the ASCENT clinical trials BMS-986446 (formerly PRX005): Bristol Myers Squibb continues to enroll the ongoing Phase 2 Target Tau-1 clinical trial in approximately 475 patients with early Alzheimer’s disease; primary completion expected in 2027 (NCT06268886)....PRX123: Continuing to optimize capital allocation across our robust R&D pipeline, Prothena expects to update plans for Phase 1 clinical trial by year-end 2025....Prasinezumab: Roche will continue to evaluate data from PADOVA and will work together with health authorities to determine next steps around mid-year 2025."

New P1 trial • P1 data • P2b data • Trial completion date • Alzheimer's Disease • Parkinson's Disease

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