Foslevodopa 2.4g/10ml / Foscarbidopa 120mg/10ml solution for infusion vials

BackgroundDevice-aided therapies, such as levodopa-and apomorphine-based infusion pumps, are widely used for managing patients with Parkinson's disease (PD) with symptoms inadequately controlled by oral medications. Cognitive impairment is a critical factor in selecting an appropriate therapy; however, the effects of levodopa/carbidopa intestinal gel (LCIG) and continuous subcutaneous apomorphine infusion (CSAI) on cognitive function remain debated.ObjectiveThe aim of this review is twofold: i) to provide a comprehensive analysis of the short-term benefits of device-aided infusion therapies on cognitive function, and ii) to evaluate their impact on long-term cognitive trajectories.MethodsA systematic literature search was conducted following PRISMA guidelines in PubMed, CINAHL, Cochrane, EMBASE, and MEDLINE. Narrative synthesis was applied to summarize results.ResultsOut of 1911 studies, 33 were included in this systematic review according to the selected criteria. No studies examined the effects of the newly introduced Foslevodopa/Foscarbidopa (LDp/CDp) nor levodopa/entacapone/carbidopa intestinal gel (LECIG) pump therapy. Seventeen studies addressed the short-term effects of CSAI; seven reported cognitive slowing and two were suggestive of positive effects. Only two studies assessed its impact on long-term cognitive trajectory, showing no significant changes. Thirteen studies examined LCIG's short-term effects; seven reported cognitive changes, with some decreases in executive functions. Two studies explored its long-term cognitive impact, with one reporting improvements.ConclusionsThe cognitive effects of device-aided treatments in PD show substantial variability, and their impact on cognitive function, processing speed, attention, and memory is inconsistent, with some studies reporting impairments and others indicating stability or slight improvements. The heterogeneity in study designs, neuropsychological assessments and coexisting vascular and amyloid pathology further complicates interpretation, underscoring the need for more controlled investigations.

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BackgroundMany Parkinson's disease patients receiving oral levodopa/carbidopa experience a troublesome wearing off effect. Higher doses to mitigate OFF-time are limited by adverse effects occurring at peak dopamine levels, particularly dyskinesia. A novel strategy to reduce OFF-time without increasing peak dopamine levels is the continuous subcutaneous infusion of levodopa/carbidopa, or their prodrug equivalents foslevodopa/foscarbidopa.ObjectivesAssess whether subcutaneous infusion therapies safely reduce OFF-time and improve quality of life scores compared to oral levodopa/carbidopa.MethodsWe searched MEDLINE, Embase, CENTRAL and ICTRP up to 28th October 2024 for clinical trials comparing subcutaneous infusions of levodopa or foslevodopa to oral levodopa in Parkinson's disease.ResultsScreening of 1114 records identified seven studies in which 725 patients received subcutaneous infusion regimens of levodopa/carbidopa (ND0612) (407 patients) or foslevodopa/foscarbidopa (318 patients). Moderate quality evidence indicated subcutaneous infusion reduced the daily duration of OFF-time by 1.98 h (p = 0.0004). Moderate quality evidence indicated improvements in health-related quality of life score PDQ-39 (p = 0.0003) and sleep score PDSS-2 (p = 0.02), but an increase in the rate of treatment-emergent adverse events, mostly related to the infusion site (p = 0.04).ConclusionsSubcutaneous infusion therapies produce a clinically and statistically significant reduction in the duration of OFF-time experienced by patients with Parkinson's disease, compared to oral levodopa/carbidopa. Patient experience is improved by a statistically, but not clinically, significant degree. There are increased adverse events, mostly related to the infusion site. Overall, subcutaneous infusion regimens could provide a meaningful alternative for Parkinson's disease patients who experience severe motor fluctuations with existing levodopa formulations.

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BackgroundParkinson disease affects approximately 6.1 million people worldwide. Although levodopa remains the most effective symptomatic therapy, long-term oral treatment commonly leads to motor fluctuations and dyskinesias that impair quality of life. Continuous subcutaneous levodopa infusion therapies have emerged as less-invasive strategies to provide continuous dopaminergic stimulation and reduce motor complications.MethodsThis systematic review evaluated the efficacy and safety of continuous subcutaneous levodopa infusion therapies, including ND0612 and foslevodopa/foscarbidopa (ABBV-951), in advanced Parkinson disease (APD). Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines, PubMed, Scopus, Web of Science, and Google Scholar were searched from inception to April 2026. Observational studies assessing continuous subcutaneous levodopa infusion in adults with APD and motor fluctuations were included. Ten studies comprising 867 patients met the inclusion criteria.ResultsAcross studies with follow-up up to 36 months, continuous subcutaneous infusion reduced daily OFF time by approximately 2.0 to 3.5 hours and increased ON time without troublesome dyskinesia. Quality of life scores improved by 5.6 to 10.8 points on Parkinson Disease Questionnaire measures. Infusion-site reactions (ISRs) were the most common adverse events, occurring in 42% to 92% of patients, though most were mild to moderate. Severe ISRs leading to discontinuation occurred in 5% to 12% of patients. ABBV-951 demonstrated numerically lower ISR rates than ND0612 in real-world settings. Systemic adverse events were generally comparable to oral levodopa therapy.ConclusionObservational evidence supports continuous subcutaneous levodopa infusion therapies as effective options for reducing motor fluctuations in APD, with sustained benefits reported up to 36 months. ISRs remain the principal tolerability concern, but severe discontinuation-related events are uncommon. Further comparative and long-term studies are needed to better define safety, efficacy, and real-world applicability across diverse populations.

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BackgroundMotor fluctuations represent a major therapeutic challenge in Parkinson's disease, particularly among individuals on long-term levodopa therapy. Although diverse pharmacological and device-aided strategies are available, their comparative efficacy, functional benefits, and real-world accessibility-especially in low- and middle-income countries (LMICs)-remain inadequately characterised.MethodologyWe conducted a systematic review of randomised controlled trials, comparative effectiveness studies, and high-quality observational cohorts evaluating pharmacological, surgical, and experimental interventions for motor fluctuations in Parkinson's disease. PubMed and Scopus were searched through 31 May 2025. Eligible studies enrolled adults with idiopathic Parkinson's disease experiencing motor fluctuations despite levodopa therapy and reported outcomes related to OFF/ON-time duration, functional disability (UPDRS-II), and health-related quality of life (PDQ-39 or EQ-5D). Risk of bias was assessed using validated tools, and the certainty of evidence was graded using the GRADE approach. In parallel, we conducted a comparative analysis of drug accessibility across nine Latin American countries (Argentina, Brazil, Chile, Colombia, Costa Rica, Guatemala, Mexico, Panama, and Peru) and the United States, assessing marketing authorisation status and Purchasing Power Parity (PPP)-adjusted prices per Defined Daily Dose (DDD).ResultsNinety-two studies met the inclusion criteria. High-certainty evidence supports the efficacy of extended-release levodopa (IPX066), opicapone, pramipexole, rotigotine, and safinamide in reducing OFF-time, although improvements in functional disability and quality of life were modest or inconsistent. Moderate-certainty evidence supports device-aided therapies, including levodopa-carbidopa intestinal gel (LCIG), subcutaneous foslevodopa-foscarbidopa, and continuous apomorphine infusion, which achieved larger effects on OFF-time and functional outcomes. Deep brain stimulation (DBS) of the globus pallidus internus was adequate but limited by cost and availability in LMICs. The Latin American analysis revealed substantial cross-country disparities: the United States had the widest therapeutic portfolio (19 approved drugs) and generally lower PPP-adjusted prices for advanced formulations. In contrast, several newer therapies-such as IPX066, opicapone, istradefylline, and foslevodopa-foscarbidopa-were unavailable in most Latin American markets, and price differentials for controlled-release or add-on therapies were often several-fold higher after PPP adjustment.ConclusionWhile multiple pharmacological and device-based interventions effectively reduce OFF-time in Parkinson's disease, their real-world impact is constrained by uneven global access and affordability. The Latin American region exemplifies these disparities, with limited regulatory availability, heterogeneous pricing, and insufficient inclusion of novel agents in national formularies. Integrating efficacy evidence with accessibility analyses highlights the need for coordinated regional policies-centred on price regulation, health technology assessment, and equitable funding mechanisms-to ensure that advances in treatment translate into meaningful improvements in function and quality of life for patients with Parkinson's disease worldwide.

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Abstract Background As Parkinson's disease (PD) progresses, managing symptoms becomes increasingly difficult. Foslevodopa/foscarbidopa (LDp/CDp), a 24‐hour/day continuous subcutaneous infusion of levodopa/carbidopa (LD/CD) prodrugs, improves motor complications. The feasibility and sustainability of LDp/CDp monotherapy warrants investigation. Objective The aim was to report the efficacy and safety of LDp/CDp monotherapy and combination therapy. Methods This post hoc analysis assessed patients with PD and ≥2.5 “Off” hours/day receiving LDp/CDp monotherapy or combination therapy in 3 trials: a 12‐week randomized active‐controlled trial (RCT) comparing LDp/CDp with oral immediate‐release LD/CD (NCT04380142), a 52‐week open‐label trial of LDp/CDp (NCT03781167), and its 96‐week open‐label extension study (OLE; NCT04379050). Monotherapy was defined as receiving LDp/CDp without concomitant PD medications; combination therapy was defined as receiving LDp/CDp with other PD medications. Results In the RCT, 74 of 141 patients received LDp/CDp. The 52‐week trial enrolled 244 patients; 129 entered the OLE. Of LDp/CDp‐treated patients, 19 of 74 (25.7%) in the RCT, 49 of 244 (20.1%) in the 52‐week trial, and 46 of 129 (35.7%) in the OLE received monotherapy. In the RCT, mean (standard deviation) change from baseline to week 12 in “Off” time was −4.5 (4.4) and −3.0 (3.5) hours for monotherapy and combination therapy, respectively; +4.1 (3.7) and +3.1 (3.6) hours for “On” time without troublesome dyskinesia; and +4.0 (3.6) and +4.0 (3.9) hours for “On” time without dyskinesia. Efficacy was similar in open‐label trials. Improvements in the Movement Disorder Society‐Unified Parkinson's Disease Rating Scale Part II, 39‐item Parkinson's Disease Questionnaire, Parkinson's Disease Sleep Scale‐2 scores, and overall safety were comparable between monotherapy and combination therapy groups. Conclusions LDp/CDp monotherapy treatment may be suitable for up to 96 weeks.

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IntroductionWe evaluated continuous subcutaneously administered foslevodopa/foscarbidopa (LDp/CDp) in younger patients earlier within advanced Parkinson's disease (aPD).MethodsThis phase 3 trial included patients aged ≥ 30 years with levodopa-responsive PD, Mini-Mental State Examination score ≥ 24, and levodopa equivalent dose ≥ 400 mg/day. Patients were considered by the investigator as inadequately controlled on current oral/transdermal therapy and experienced ≥ 2.5 h/day "Off" time, with recognizable "On"/"Off" states. Patients were randomized (1:1) to LDp/CDp plus placebo capsules or orally administered immediate-release levodopa/carbidopa plus placebo infusion. This post hoc exploratory analysis focused on younger patients (≤ 65 years) earlier within aPD (Hoehn and Yahr stage ≤ 2 ["On" state], ≤ 5 years since motor fluctuations started). Outcomes included change from baseline (CFB) to week 12 in "Off" and "On" time, Movement Disorder Society Unified PD Rating Scale (MDS-UPDRS) II, 39-item PD Questionnaire (PDQ-39), and PD Sleep Scale-2 (PDSS-2).ResultsTwenty-six patients met subgroup criteria (LDp/CDp, n = 13; orally administered levodopa/carbidopa, n = 13). Despite small sample sizes, at week 12, LDp/CDp was associated with significantly greater improvements in "Off" time (mean [SD] CFB - 3.7 [3.1] vs - 1.6 [2.9] h; P = 0.0011), "On" time without troublesome dyskinesia (+ 3.9 [3.3] vs + 1.4 [3.8] h; P = 0.0011), and PDSS-2 (- 6.4 [4.6] vs - 1.8 [3.1]; P = 0.0220) vs orally administered levodopa/carbidopa. Mean (SD) CFB to week 12 (LDp/CDp vs orally administered levodopa/carbidopa) was + 4.2 (2.8) vs + 1.9 (4.6) h for "On" time without dyskinesia (P = 0.0878), - 3.0 (6.4) vs - 0.9 (3.5) for MDS-UPDRS II (P = 0.3539), and - 9.9 (7.4) vs - 1.9 (9.4) for PDQ-39 (P = 0.0534). For most assessments, treatment differences were numerically larger in the subgroup vs the overall population. Safety findings were consistent with the overall population.ConclusionsLDp/CDp was associated with significantly greater improvements in motor function and sleep vs orally administered levodopa/carbidopa in younger patients earlier within aPD whose symptoms were inadequately controlled by oral/transdermal therapies. Larger real-world studies are needed to confirm findings.Trial registrationClinicalTrials.gov identifier, NCT04380142.

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IntroductionPeople with advanced Parkinson's disease (aPD) frequently experience unpredictable "Off" time and debilitating motor fluctuations. Foslevodopa/foscarbidopa (LDp/CDp), a levodopa/carbidopa (LD/CD) prodrug, is delivered as a 24-h continuous subcutaneous infusion. This post hoc analysis evaluated the efficacy of LDp/CDp in achieving consistent motor symptom control and stable motor states in people with aPD.MethodsDiaries of people with aPD treated with LDp/CDp participating in a 12-week, phase 3, randomized controlled trial (RCT) were evaluated versus oral LD/CD, and in a 52-week open-label, single-arm trial (OLT) with LDp/CDp alone. Motor symptom control was assessed by frequency (30-min intervals) and duration (4-h blocks) of motor states (good "On" time [without dyskinesia or troublesome dyskinesia] or "Off" time) over a 16-h waking day. Motor state stability was evaluated by changes in daily motor fluctuations and extreme fluctuations (defined as transition from "Off" to "On" with troublesome dyskinesia, or vice versa). Outcomes were analyzed using adjusted regression models.ResultsAnalysis included 47 (RCT) and 55 (OLT) people with aPD on LDp/CDp. In the RCT, LDp/CDp had an approximately 1-h gain in good "On" time in the mornings versus a quarter-hour gain for those on LD/CD (P = 0.001), with > 80% of participants on LDp/CDp waking up in good "On." At week 12, fewer motor fluctuations/day occurred with LDp/CDp versus LD/CD (3.2 vs 5.3; nominal P = 0.001), and twice as many participants on LDp/CDp had ≤ 3 fluctuations/day (53.2% vs 25.8%). In the OLT, the results seen at 12 weeks were sustained through week 52, with fewer mean fluctuations/day (3.1) than baseline (7.4) and more participants reporting ≤ 3 fluctuations/day at 52 weeks (66.6%) versus baseline (12.9%).ConclusionLDp/CDp provided consistent motor symptom control throughout the day, enhanced motor state stability, and reduced motor fluctuation, highlighting LDp/CDp's potential to significantly improve the management of unpredictable motor states and overall quality of life for people with aPD.Trial informationClinicaltrials.gov ID: NCT04380142, NCT03781167.

Abstract licence: CC BY-NC 4.0

BackgroundParkinson's disease (PD) incidence has risen by more than eightfold in the United Arab Emirates (UAE) between 1990 and 2019, representing one of the highest increases globally and creating substantial pressure on a fragmented, multi-payer health system. Region-specific guidance has been lacking, leading clinicians to extrapolate from international guidelines that do not fully address formulary heterogeneity, advanced therapy centralization, and cultural factors.MethodsUnder the auspices of the Emirates Neurology Society, a national taskforce of 10 specialists representing major PD centers across the UAE used a three-round modified Delphi process informed by systematic literature review and key randomized controlled trials. Recommendations were graded using a GRADE-aligned system (A-C, Good Practice Points) and adapted to UAE formulary, service configuration, and cultural context.ResultsConsensus was achieved on 146 recommendations across eight domains: (1) mandatory adoption of MDS-2015 diagnostic criteria; (2) age-stratified pharmacologic algorithms with levodopa as first-line for older or cognitively vulnerable patients; (3) structured non-motor symptom management; (4) rehabilitation and UAE cultural lifestyle adaptations including Ramadan fasting management, DBS considerations in women, family-centered care, and multilingual practice; (5) advanced therapy referral using the 5-2-1 rule integrated with the Making Informed Decisions to Aid Timely Management of Parkinson's Disease (MANAGE-PD) tool, with five device-aided options (subcutaneous foslevodopa/foscarbidopa, apomorphine SC- subcutanous, LCIG- Levodopa Carbidopa Intestinal Gel, DBS- Deep Brain Stimulation, MRgFUS- MRI guided focussed ultrasound) presented through shared decision-making; (6) a three-tier service model; (7) UAE formulary mapping; and (8) center accreditation and registry metrics. Advanced therapies are centralized in accredited centers with clear minimum volume and multidisciplinary staffing criteria.ConclusionThese UAE consensus recommendations provide a pragmatic, context-adapted framework for PD management, emphasizing structured diagnosis, age-appropriate pharmacotherapy, systematic use of MANAGE-PD and 5-2-1 for advanced therapy referral, culturally sensitive practice adaptations, and a three-tier network model integrated through the Malaffi health information exchange and a planned national PD registry.

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