Xadago (safinamide) / Meiji Seika, Eisai, Valeo Pharma, Zambon, Newron, Sun Pharma, Supernus Pharma - LARVOL DELTA

EFFECTS OF MAO-B AND COMT INHIBITORS ON SLEEP DISTURBANCES IN PARKINSON'S DISEASE: A NETWORK META-ANALYSIS (ADPD 2026) - "Inclusion criteria involved (1) patients with PD, (2) intervention/comparator consisting of MAO-B inhibitors (safinamide, rasagiline, or selegiline) and COMT inhibitors (opicapone, entacapone, or tolcapone), and (3) outcomes of improvement in parameters for subjective and objective sleep in randomized controlled trials and cohort studies. A total of 529 articles were identified during the initial search, and we ultimately conducted an NMA focusing on the final seven studies. Evidence has shown that safinamide is effective in improving objective sleep parameters in patients with PD. However, given the paucity of evidence and controlled, long-term studies, the effects of MAO-B and COMT inhibitors on sleep disturbances remain unclear. More high-quality studies will be needed and should enable clinicians to provide personalized medicine based on sleep profiles."

Retrospective data • CNS Disorders • Movement Disorders • Parkinson's Disease • Sleep Disorder • COMT

EFFICACY OF MAO-B AND COMT INHIBITORS ON QUALITY OF LIFE IN PATIENTS WITH PARKINSON'S DISEASE: A BAYESIAN NETWORK META-ANALYSIS (ADPD 2026) - "Randomized controlled trials evaluating QoL using PDQ-39 or PDQ-8 in patients treated with MAO-B inhibitors (rasagiline, selegiline, safinamide) or COMT inhibitors (entacapone, opicapone, tolcapone) were included. This network meta-analysis provides evidence that MAO-B inhibitors, particularly rasagiline and safinamide, may offer broader QoL benefits in patients with PD, especially in NMS such as emotional well-being. These findings support a more symptom-oriented and individualized treatment approach should be provided to patients with PD. Further well-designed head-to-head studies using standardized QoL measures and extended follow-up are needed to confirm these findings and guide clinical practice."

HEOR • Retrospective data • CNS Disorders • Movement Disorders • Parkinson's Disease • COMT

TWO UNIQUE SAFETY PATTERNS OF SAFINAMIDE AS AN ADJUNCT TO LEVODOPA MONOTHERAPY FOR ASIAN PATIENTS WITH PARKINSON'S DISEASE AND WEARING OFF (ADPD 2026) - "Safinamide 100 mg/day may benefit PD patients, particularly those aged 75 years and older. The findings support the safety of continued use of safinamide at this dose and emphasize the importance of early monitoring."

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

COMPARATIVE COGNITIVE EFFECTS OF MAO-B INHIBITORS IN PARKINSON'S DISEASE (ADPD 2026) - "We aimed to compare the effects of selegiline, rasagiline, and safinamide on global cognitive function and specific cognitive domains in patients with PD. Comprehensive literature searches in PubMed, Embase, and Cochrane Library identified randomized controlled trials (RCTs) assessing cognitive outcomes in PD patients treated with MAO-B inhibitors. Among MAO-B inhibitors, only rasagiline was associated with enhanced overall cognitive performance in PD, but domain-specific improvements were largely absent. These findings indicate that cognitive benefits beyond motor symptom control remain limited, and highlight the need for future long-term studies with domain-focused assessments to delineate therapeutic roles for MAO-B inhibitors in cognitive outcomes for PD patients."

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

Effect of Safinamide on Sleep Quality in Patients With Parkinson's Disease (clinicaltrials.gov) - P4 | N=11 | Terminated | Sponsor: Alain Kaelin | N=23 ➔ 11 | Recruiting ➔ Terminated; insufficient eligible patients for enrollment

Enrollment change • Trial termination • CNS Disorders • Movement Disorders • Parkinson's Disease

Antiseizure Medications that Did Not Reach the Epilepsy Market: An Assessment of Factors Contributing to Their Failed Clinical Development Over the Last Three Decades. (PubMed, Drugs) - "Compounds whose development was terminated include atimepazole, beprodone, cannabidivarin, carabersat, conantokin-G, dezinamide, elpetrigine, flunarizine, fluorofelbamate, ICA-105665, isovaleramide, JNJ-40411813, losigamone, naluzotan, padsevonil, pitolisant, ralitoline, remacemide, safinamide, soretolide, talampanel, tonabersat, T2000, T2007, valnoctamide, valrocemide, VX-765, zandatrigine, zuranolone, and 534U87. In some instances, failure to pursue an epilepsy indication could be explained by prioritization of development for other neurological or psychiatric conditions. This may reflect the perception of the drug market for common epilepsies being relatively crowded, and only attractive for compounds with outstanding safety or efficacy advantages over existing medications."

Journal • Review • CNS Disorders • Epilepsy • Psychiatry

Advanced Parkinson's disease treatment patterns in Italy: results from a multicenter observational study. (PubMed, Ann Med) - "Safinamide and opicapone showed the biggest increase in use over the 3-year observation period. Maintenance of stable disease in patients with long-standing PD and fluctuations is feasible with non-invasive treatments. Accurate treatment adjustments and individualized strategies with new-generation add-on drugs may be of key importance."

Journal • Observational data • Retrospective data • Cardiovascular • CNS Disorders • Movement Disorders • Parkinson's Disease • COMT

The Safety and Efficacy of Monoamine Oxidase-B Inhibitors as Add-on Therapy to Dopamine Agonists for the Treatment of Parkinson's Disease: A Systematic Review and Network Meta-analysis of Randomized Controlled Trials (AAN 2026) - "Objective: ‎This meta-analysis aimed to examine the efficacy and safety of both irreversible and reversible monoamine oxidase B (MAO-B) inhibitors as add-on therapy in patients with Parkinson's disease.Background: Parkinson's disease (PD) is a neurodegenerative disease, treated with carbidopa/levodopa or a dopamine agonist...They can be irreversible (selegiline and rasagiline) or reversible (safinamide)... Selegiline (10mg/day) and safinamide (100mg) offer good therapeutic benefit as add-on therapy for PD. However, safinamide (100mg) has a relatively better safety profile as compared to selegiline (10mg/day). Further research should emphasize on long-term effects of these drugs through longitudinal studies focusing on patient-reported outcomes."

Retrospective data • Review • CNS Disorders • Movement Disorders • Parkinson's Disease

Efficacy of MAO-B and COMT inhibitors on quality of life in patients with Parkinson's disease: a Bayesian network meta-analysis. (PubMed, Front Neurol) - "Randomized controlled trials evaluating QoL using PDQ-39 or PDQ-8 in patients treated with MAO-B inhibitors (rasagiline, selegiline, safinamide) or COMT inhibitors (entacapone, opicapone, tolcapone) were included. Further well-designed head-to-head studies using standardized QoL measures and extended follow-up are needed to confirm these findings and guide clinical practice. Registered in PROSPERO (CRD420251013028): https://www.crd.york.ac.uk/PROSPERO/view/CRD420251013028."

HEOR • Journal • Retrospective data • Review • CNS Disorders • Movement Disorders • Parkinson's Disease • COMT

Design, synthesis and biological evaluation of donepezil-safinamide hybrids as dual AChE and MAO-B inhibitor for Alzheimer's disease treatment. (PubMed, J Enzyme Inhib Med Chem) - "Moreover, compound 28c demonstrated effective blood-brain barrier penetration, exhibited suitable stability in mouse plasma and brain homogenate, and showed a favourable safety profile both in vitro and in vivo. Furthermore, 28c could attenuate AD-related symptoms and exert hippocampal neuroprotection effect in vivo, highlighting its promise as an anti-AD candidate."

Journal • Alzheimer's Disease • CNS Disorders • Pain

An hMAO-B-activatable mitochondrial binding fluorescent probe in live-cell via enzyme-anchored and charge-driven dual targeting. (PubMed, Spectrochim Acta A Mol Biomol Spectrosc) - "Its activation mechanism was validated through safinamide-inhibition assays in both enzyme and cellular models...THT-MTP exhibited excellent mitochondrial accumulation via enzyme-anchored and charge-driven dual targeting. This work establishes a design paradigm for hMAO-B-selectvie probes combining high-precision subcellular targeting, activatable imaging capability and wash-free operation, offering a robust molecular tool for investigating hMAO-B-associated diseases."

Journal • Cardiovascular • CNS Disorders • Congestive Heart Failure • Heart Failure • Hepatology • Metabolic Disorders • Oncology

Effects of MAO-B Inhibitors on Cognition in Patients with Parkinson’s Disease: A Systematic Network Meta-Analysis. (PubMed, Mov Disord Clin Pract) - "Rasagiline may provide global cognitive benefits in PD, but MAO-B inhibitors, including rasagiline, generally did not demonstrate significant effects on individual cognitive domains. These findings suggest limited cognitive impacts of MAO-B inhibitors beyond managing the motor symptoms. Further large-scale, long-term studies using domain-specific cognitive assessments are warranted to clarify their roles in cognitive performance in patients with PD."

Journal • Retrospective data • CNS Disorders • Cognitive Disorders • Dementia • Movement Disorders • Parkinson's Disease

Integrative Human Genomic and Pharmacological Analyses Identify CACNB4 as a Druggable Target for Periodontitis. (PubMed, J Periodontal Res) - "Through MR analysis, we identified CACNB4 as a potential druggable gene for periodontitis. Among the drugs targeting CACNB4, verapamil and safinamide emerged as the most promising candidates for periodontitis treatment. Pharmacological studies further demonstrated that these agents may inhibit osteoclast differentiation by targeting CACNB4, thereby offering potential therapeutic options for periodontitis."

Journal • Dental Disorders • Periodontitis • ADAM12 • FGF2

Faith, fasting, and well-being: Emirates Neurology Society consensus guidelines on safe Ramadan fasting in Parkinson's disease. (PubMed, Front Neurol) - "Long-acting dopaminergic therapies, including Dopamine Agonists (rotigotine patches and other extended-release (ER) oral agents), adjunctive agents (opicapone, rasagilline and safinamide), and Device-Aided Treatments (DAT; subcutaneous foslevodopa-foscarbidopa, subcutaneous continous subcutaneous apomorphine infusion, levodopa-carbidopa intestinal gel and deep brain stimulation) can help stabilize motor and non-motor fluctuations. Safe Ramadan fasting in PD requires comprehensive pre-Ramadan assessment, stage-specific therapeutic strategies, and proactive management of both motor and non-motor complications. Shared decision-making that integrates medical, psychological, and religious considerations is vital to optimize patient outcomes while respecting spiritual values."

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

Treatment strategies for motor fluctuations in Parkinson's disease: a systematic review of efficacy, functionality, and drug accessibility with a focus on Latin America. (PubMed, Front Pharmacol) - "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...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...The Latin American region exemplifies these disparities, with limited regulatory availability, heterogeneous pricing, and insufficient inclusion of novel agents in national formularies...."

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

Chemometric-assisted spectrophotometric approach for stability assessment of safinamide and its synthetic precursor in antiparkinsonian formulation with sustainability profiling. (PubMed, Sci Rep) - "Furthermore, these methods can be used as a substitute for HPLC in quality control laboratories when multiple samples need to be analyzed within a short timeframe. Finally, various sustainability assessment tools were utilized to evaluate and measure the environmental background of the established methods."

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

A computational-based search of natural product derived multi-target ligands for the management of Alzheimer's and Parkinson's disease using structure-based pharmacophore modelling, virtual screening, MD docking, free energy analysis, ADMET profiling and DFT studies. (PubMed, SAR QSAR Environ Res) - "Four hits (N1-N4) displayed superior binding affinities relative to reference drugs donepezil (DNP) and safinamide (SAF). Additionally, density functional theory (DFT) studies provided insights into the electronic characteristics and reactivity of top hits. Overall, this integrated in silico approach emphasized the potential of natural scaffolds as sustainable multi-target-directed ligands (MTDLs) for AD and PD therapeutics."

Journal • Alzheimer's Disease • CNS Disorders • Movement Disorders • Pain • Parkinson's Disease • DRD2

Nocturnal Hypokinesia and Early Morning OFF in Parkinson's Disease: State-of-the-Art and Systematic Review of Treatment Availability. (PubMed, Curr Neurol Neurosci Rep) - "Pharmacologic treatments include standard and sustained-release levodopa, dopamine agonists (rotigotine, ropinirol, pramipexole, and apomorphine), MAO-B inhibitors (rasagiline, safinamide), COMT inhibitors (opicapone), and rescue therapies like inhaled or dispersible levodopa or apomorphine injection. For mild, disturbing symptoms in early PD, inhaled or dispersible levodopa or apomorphine injection are advised. In moderate to advanced stages, treatment options include long-acting dopamine agonists, MAO-B inhibitors, sustained-release levodopa, or COMT inhibitors selected based on factors such as daytime motor symptoms, and non-motor symptoms."

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

Effects of MAO-B and COMT inhibitors on sleep disturbances in Parkinson's disease: A network meta-analysis. (PubMed, J Mov Disord) - "However, in analyses of objective PSG data, safinamide was found to significantly increase REM sleep duration (mean difference, 5.70 [95% CI, 2.26, 9.14]) and decrease wake time after sleep onset (mean difference, -10.20 [-19.38, -1.02]) compared to rasagiline and placebo. Given the limited number and small scale of available trials, the overall evidence should be interpreted cautiously. Nonetheless, this analysis highlights the need for further high-quality trials focused on sleep outcomes to guide personalized use of MAO-B and COMT inhibitors for sleep disturbances in PD."

Journal • Retrospective data • CNS Disorders • Movement Disorders • Parkinson's Disease • Sleep Disorder • COMT

Inhibition of monoamine oxidase by fluorobenzyloxy chalcone derivatives. (PubMed, RSC Adv) - "Inspired by safinamide's pharmacophoric features, the study focuses on designing, synthesizing, and evaluating a novel series of fluorinated benzyloxy chalcone derivatives as selective MAO-B inhibitors...Lead compounds were stabilized in protein-ligand complexes by the π-π stacking, which enabled them to bind to the active site of hMAO-B effectively. These results suggest that FBZ6 and FBZ13 are potent reversible selective MAO-B inhibitors, and they can be used as potential agents for the treatment of neurological disorders such as Alzheimer's diseases and PD."

Journal • Alzheimer's Disease • CNS Disorders • Movement Disorders • Neuroblastoma • Oncology • Parkinson's Disease • Solid Tumor

Evaluation of novel selective MAO-B inhibitors using immobilized enzymes on magnetic beads. (PubMed, J Pharm Biomed Anal) - "The assay was qualified with toloxatone and safinamide as reference inhibitors, yielding IC50 values of 3.42 ± 0.11 µM and 33.38 ± 1.38 nM, respectively. Additionally, a collection of terpenyl-benzohydrazides was screened, identifying PQM-244 (5c) as a selective MAO-B inhibitor (IC50 = 4.17 ± 0.082 µM) with a non-competitive inhibition mechanism (Ki = 2.28 ± 0.38 µM). These findings suggest that 5c (PQM-244) has significant potential to contribute to developing selective MAO-B inhibitors for Parkinson's disease therapy."

Journal • Cardiovascular • CNS Disorders • Depression • Movement Disorders • Parkinson's Disease • Psychiatry

Treatment Stability Across Different ADD-ON Therapies in Fluctuating Parkinson's Disease (MDS Congress 2025) - "Objective: This study investigates the efficacy and tolerability of selegiline (SL), rasagiline (RS), safinamide (SF), and opicapone (OP) in fluctuating PD patients, focusing on treatment stability and demographic influences. No single add-on therapy demonstrated superior stability, highlighting comparable efficacy across options. Sex significantly influenced therapy adjustments, with females requiring more frequent modifications. These findings underscore the importance of personalized treatment strategies in fluctuating PD management."

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

Safinamide as an Adjunct Therapy for Motor Symptoms and ON-Time Extension in Parkinson's Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials (MDS Congress 2025) - "Safinamide, at both 50 mg and 100 mg doses, significantly improves motor function and extends ON-time in PD patients with motor fluctuations. These findings support its role as an effective adjunct therapy to levodopa, warranting further investigation in long-term studies. Figure 1"

Retrospective data • Review • CNS Disorders • Movement Disorders • Parkinson's Disease

DIFFERENTIAL EFFECTS OF SAFINAMIDE TREATMENT (ACUTE, SUB-ACUTE AND CHRONIC) ON MICROGLIAL POLARIZATION IN A RAT MODEL OF TRANSIENT ISCHEMIC STROKE (WCN 2025) - "Post-stroke safinamide treatment attenuated neurological damage by switching microglial polarization towards anti-inflammatory M2 phenotype. Further exploration of safinamide through molecular studies can pave a way for repurposing it in ischemic stroke."

Preclinical • CNS Disorders • Movement Disorders • Parkinson's Disease • ARG1 • IL10 • IL1B • TGFB1 • TNFA

ADD-ON THERAPY WITH SAFINAMIDE AND AMANTADINE AMONG AMBULATORY FILIPINO PARKINSON'S DISEASE FLUCTUATORS: A SINGLE-CENTER EXPLORATORY STUDY (WCN 2025) - "Safinamide and Amantadine were effective adjunctive therapies to DRT in improving ON-times among ambulatory Filipino PD patients with motor fluctuations."

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