sarizotan (EMD128130) / Newron - LARVOL DELTA

Efficacy and Safety of Twelve Anti-Dyskinetic Drugs in Parkinson's Disease: A Bayesian Network Meta-Analysis of Randomized Controlled Trials. (PubMed, Eur J Neurol) - "Amantadine ER improved dyskinesia significantly versus amantadine IR. Both formulations of amantadine were superior as OFF time-reducing agents compared to other anti-dyskinetic drugs, whereas amantadine IR non-significantly reduced OFF time versus amantadine ER."

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

Not Everything Is Behavioral: A Case Report and Systematic Review of Treatments for Severe Apneic Spells in ASD (APA 2025) - "The literature review presented here resulted in prescribing topiramate and brivaracetam. Literature search resulted in 55 publications with 9 (5 case reports, 4 reviews; total n = 36) eligible for inclusion. Treatments identified included acetazolamide, topiramate, carbamazepine, and sarizotan. Topiramate and acetazolamide were most commonly successful."

Case report • Clinical • Review • Autism Spectrum Disorder • CNS Disorders • Developmental Disorders • Genetic Disorders • Movement Disorders • Psychiatry

Rett Syndrome: The Emerging Landscape of Treatment Strategies. (PubMed, CNS Drugs) - "While some of these have been unrewarding such as sarizotan, others have been quite promising including the approval of trofinetide by the FDA in 2023 as the first agent available for specific treatment of RTT. Blarcamesine has been trialed in phase 3 trials, 14 agents have been studied in phase 2 trials, and 7 agents are being evaluated in preclinical/translational studies...Taken together, progress in understanding and treating RTT over the past 40 years has been remarkable. This suggests that further advances can be expected."

Journal • Review • CNS Disorders • Developmental Disorders • Epilepsy • Gene Therapies • Mood Disorders • Movement Disorders • Orthopedics • Parkinson's Disease • Psychiatry • Rare Diseases

Effect of Positive Allosteric Modulation and Orthosteric Agonism of Dopamine D2-like Receptors on Respiration in Mouse Models of Rett Syndrome. (PubMed, Respir Physiol Neurobiol) - "Sarizotan, a serotonin 5-HT1a and dopamine D2-like receptor agonist, reduces the incidence of apneas and irregular breathing in mouse models of RTT (Abdala et al., 2014). These results suggest that D2-like receptors could contribute to the positive effects of sarizotan in the correction of respiratory abnormalities in Rett syndrome. However, positive allosteric modulation of D2-like receptors alone was not sufficient to evoke these effects."

Journal • Preclinical • Autism Spectrum Disorder • Developmental Disorders • Genetic Disorders • Movement Disorders

MAL2 reprograms lipid metabolism in intrahepatic cholangiocarcinoma via EGFR/SREBP-1 pathway based on single-cell RNA sequencing. (PubMed, Cell Death Dis) - "Lastly, we conducted a virtual screen to identify sarizotan, a small molecule inhibitor of MAL2, and successfully validated its ability to inhibit MAL2 function. Our findings highlight the tumorigenic role of MAL2 and its involvement in cisplatin sensitivity, suggesting the potential for novel combination therapeutic strategies in ICC."

Journal • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Metabolic Disorders • Oncology • Solid Tumor • EGFR • MAL2

Repurposing Drugs for Inhibition against ALDH2 via a 2D/3D Ligand-Based Similarity Search and Molecular Simulation. (PubMed, Molecules) - "Sarizotan (q = +1 e) and Netarsudil (q = 0/+1 e) displayed a strong binding strength with ALDH2 as well, whereas they displayed a shallow penetration into the substrate-binding tunnel of ALDH2 and could not fully occupy it. The electrostatic attraction with positively charged compounds, however, yielded very strong binding results with ALDH2. These findings reveal a deficiency in the modeling of electrostatic interactions (in particular, between charged moieties) in the virtual screening via the 2D/3D similarity search and molecular docking with the Vina scoring system."

Journal • Addiction (Opioid and Alcohol) • Tobacco Addiction • ALDH2

Structure-based virtual screening and molecular docking approaches to identify potential inhibitors against KIF2C to combat glioma. (PubMed, J Biomol Struct Dyn) - "The docking results were examined using the Glide gscore, and the best binding compounds (Rimacalib and Sarizotan) were chosen to test their stability with KIF2C protein through molecular dynamics (MD) simulation...The MM/GBSA binding free energies showed a considerable energy contribution in the binding of hits with the KIF2C. Collectively, these findings strongly suggest the potential of the lead compounds to inhibit the biological function of KIF2C, emphasizing the need for further investigation in this area.Communicated by Ramaswamy H. Sarma."

Journal • Brain Cancer • CNS Tumor • Glioma • Lung Cancer • Oncology • Solid Tumor • KIF2C

Tandem InCl-Promoted Hydroperoxide Rearrangements and Nucleophilic Additions: A Straightforward Entry to Benzoxacycles. (PubMed, J Org Chem) - "This article describes the tandem process between a Hock or Criegee oxidative cleavage and a nucleophilic addition onto the oxocarbenium species (in particular a Hosomi-Sakurai-type allylation), under InCl catalysis. It was applied to the synthesis of 2-substituted benzoxacycles (chromanes and benzoxepanes), including a synthesis of the 2-(aminomethyl)chromane part of sarizotan, and a total synthesis of erythrococcamide B."

Journal

5-HT agonists for levodopa-induced dyskinesia in Parkinson's disease. (PubMed, Neurodegener Dis Manag) - "Clinical trials testing 5-HT agonists have yielded inconsistent results in alleviating dyskinesia, especially that the antidyskinetic benefit observed was often accompanied by an adverse effect on motor function. In this article, we summarize and analyze the various clinical trials performed with 5-HT agonists in PD patients with dyskinesia and offer perspectives on the future of this class of agents in PD."

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

Current Therapies in Clinical Trials of Parkinson's Disease: A 2021 Update. (PubMed, Pharmaceuticals (Basel)) - "In 1970, the United States Food and Drug Administration approved the drug levodopa as a dopamine replacement to manage PD motor symptoms; levodopa-carbidopa combination became commercialized in 1975...The three phase-III trials use embryonic dopamine cell implant, 5-HT receptor agonist (sarizotan), and adenosine A receptor antagonist (caffeine)...Additionally, we discuss the most potent drug or therapy among these trials. By systematically updating the current trial status and analyzing the therapeutic strategies, we hope this review can provide new ideas and insights for PD therapy development."

Clinical • Journal • Review • CNS Disorders • Gene Therapies • Movement Disorders • Parkinson's Disease

Evaluation of the Efficacy, Safety, and Tolerability of Sarizotan in Rett Syndrome With Respiratory Symptoms (clinicaltrials.gov) - P2/3; N=129; Terminated; Sponsor: Newron Pharmaceuticals SPA; Trial completion date: Apr 2019 ➔ Jul 2020; Active, not recruiting ➔ Terminated; The study did not demonstrate evidence of efficacy on the primary or secondary efficacy variables

Clinical • Trial completion date • Trial termination • Developmental Disorders • Movement Disorders

Newron Announces Half-Year 2020 Results (Businesswire) - "Sarizotan (Rett syndrome): Newron terminated development program....Company to share learnings from the Rett Syndrome International Burden of Illness study, and is evaluating passing on the study to another pharmaceutical company for completion....Evenamide: Newron remains confident that it is on track to initiate the Phase III studies with evenamide in Q2 2021. In key territories, the Company continues to expect to commercialize evenamide itself in the treatment-resistant schizophrenia indication. For the indication of patients showing inadequate response to their current atypical antipsychotics and experiencing worsening of psychosis, Newron is currently evaluating potential options for partnering/co-development."

Licensing / partnership • New P3 trial • CNS Disorders • Schizophrenia

Non-dopaminergic Alterations in Depression-Like FSL Rats in Experimental Parkinsonism and L-DOPA Responses. (PubMed, Front Pharmacol) - "FSL rats showed a potentiated tremorgenic response to tacrine, a cholinesterase inhibitor used experimentally to induce 6 Hz resting tremor reminiscent of parkinsonian tremor...However, following chronic treatment with L-DOPA, FRL rats developed sensitization of turning and abnormal involuntary movements (AIMs); these effects were counteracted by the anti-dyskinetic 5-HT agonist/D partial agonist sarizotan...The marked behavioral difference between the FRL and FSL rats was paralleled with the striatal expression of the established marker, c-fos, but also the GABAergic transporter (vGAT), and a hitherto unknown marker, tamalin, that is known to regulate mGluR5 receptor function and postsynaptic organization. This study demonstrates that behavioral and transcriptional responses of non-dopaminergic systems to experimental parkinsonism and L-DOPA are modified in a genetic rat model of depression."

Journal • Preclinical • CNS Disorders • Depression • Gene Therapies • Mood Disorders • Movement Disorders • Parkinson's Disease

Potent hERG channel inhibition by sarizotan, an investigative treatment for Rett Syndrome. (PubMed, J Mol Cell Cardiol) - "This action and consequent ventricular AP prolongation occur at concentrations relevant to those proposed to treat breathing dysrhythmia in RTT. Sarizotan should only be used in RTT patients with careful evaluation of risk factors for QT prolongation."

Journal • CNS Disorders • Developmental Disorders • Psychiatry

Newron reports top-line results from its STARS study evaluating sarizotan in patients with Rett syndrome (Businesswire) - P=2/3, N=129; STARS (NCT02790034); Sponsor: Newron Pharmaceuticals SPA; "Newron Pharmaceuticals S.p.A....announced today that top-line results from its STARS clinical study evaluating sarizotan in patients with Rett syndrome did not demonstrate evidence of efficacy on the primary or secondary efficacy variables. Consequentially, Newron has decided to terminate this development program. The STARS (Sarizotan for the Treatment of Apneas in Rett Syndrome) clinical study qualified and enrolled 129 Rett syndrome patients in 14 centres throughout the US, Europe, Asia and Australia for the six-month clinical trial. Newron plans to work with the Rett research community and families to share learnings..."

Discontinued • P2/3 data • CNS Disorders

Newron updates on STARS study FDA interaction (Businesswire) - "Newron Pharmaceuticals S.p.A....announces that it has received the final minutes from a meeting with the U.S. Food and Drug Administration (FDA) held on February 5, 2020. In the meeting, the parties discussed the Company’s statistical analysis plan (SAP), submitted to the FDA in September 2019, and the FDA’s recommendations. The clinical database for the STARS study remains locked and blinded....'We expect to be able to share the topline results of this important study with the global Rett community and the markets in Q2 2020.'"

FDA event • P2/3 data

Newron announces 2019 financial results and provides outlook for 2020 (Businesswire) - "Newron successfully completed enrollment of 129 patients in the STARS Phase III study...Newron participated in a meeting with the U.S. Food and Drug Administration (FDA) to discuss the STARS study statistical analysis plan, ahead of STARS clinical trial data unblinding, and now expects top-line results in H1 2020. The FDA granted Rare Pediatric Disease Designation for sarizotan, following an earlier decision to grant sarizotan Orphan Drug Designation."

Enrollment closed • FDA event • P3 data: top line

Evaluation of the Efficacy, Safety, and Tolerability of Sarizotan in Rett Syndrome With Respiratory Symptoms (clinicaltrials.gov) - P2/3; N=129; Active, not recruiting; Sponsor: Newron Pharmaceuticals SPA; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed