evenamide (NW-3509) / Newron - LARVOL DELTA

Evenamide as an add-on to antipsychotics demonstrates significant efficacy in patients with schizophrenia in a potentially pivotal randomized placebo-controlled trial (ECNP 2024) - "This is the first randomized, placebo-controlled trial to demonstrate that glutamate modulation is effective in managing inadequate response to antipsychotics in patients with schizophrenia and that evenamide should become the first-choice treatment for such patients."

Clinical • CNS Disorders • Epilepsy • Psychiatry • Schizophrenia

Evenamide as add-on to antipsychotics in treatment-resistant schizophrenia: design of a potentially pivotal, phase 3, international, randomized, double-blind, placebo-controlled trial (ECNP 2024) - "The usage of clozapine, the only drug approved for TRS, remains remarkably low due to its severe side effects. Positive Results would confirm the benefit seen in the pilot study, paving the way for a new treatment paradigm for patients with TRS."

Clinical • P3 data • CNS Disorders • Psychiatry • Schizophrenia

Achievement of clinically meaningful response and remission in treatment-resistant schizophrenia patients: Results from a long-term international study with evenamide add-on (ECNP 2024) - "Study 014/015 was a 1-year, randomized, open-label, rater-blinded, international study in patients with TRS not responding to a therapeutic dose of an AP (except clozapine). The addition of evenamide to APs in TRS patients resulted in clinically important improvement of symptoms of psychosis to such an extent that a meaningful proportion of patients no longer met the criteria for TRS, and a subgroup eventually achieved remission. These Results are unique for a NCE that acts solely through modulation of glutamate. If confirmed in a phase III, double-blind, placebo-controlled trial, these Results would indicate the necessity of glutamate modulation for the optimal treatment of TRS patients."

Clinical • CNS Disorders • Psychiatry • Schizophrenia

Evenamide as an add-on to antipsychotics demonstrates significant efficacy in patients with schizophrenia in a pivotal randomized placebo-controlled trial (ECNP 2024) - "During this 1-year period, the benefits on symptoms of psychosis (PANSS), severity of disease (CGI-S) and global evaluation (CGI-C) continued to show increasing improvement with time.New, breakthrough and compelling Results from a phase 3, international, randomized, double-blind, placebo-controlled, 4-week trial, demonstrated the safety and statistically significant efficacy of evenamide 30 mg bid as add-on in patients with chronic schizophrenia poorly responding to their antipsychotic and thus met both primary (PANSS) and key secondary endpoints (CGI-S). Evenamide was well tolerated with a low dropout rate (4%) and adverse dropout rate (1%), and low incidence of TEAEs, comparable rates on evenamide and placebo.This is the first potentially pivotal trial to demonstrate the benefit of adding an antipsychotic to poor-responders: evenamide is the first NCE glutamate modulator that benefits patients with schizophrenia whose symptoms are not adequately controlled by SGAs..."

Clinical • CNS Disorders • Psychiatry • Schizophrenia

Evenamide, as an add-on to antipsychotics, produces long-lasting clinically meaningful benefit and converts treatment-resistant schizophrenia (TRS) patients into a responsive state: 6-month results from an ongoing international randomized study (CINP 2024) - No abstract available

Clinical • CNS Disorders • Psychiatry • Schizophrenia

Evenamide as add-on treatment for treatment-resistant schizophrenia (TRS) patients not benefiting from antipsychotics: design of a phase 3, potentially pivotal, international, randomized, double-blind, placebo-controlled clinical trial (CINP 2024) - No abstract available

Clinical • P3 data • CNS Disorders • Psychiatry • Schizophrenia

Evenamide as add-on treatment for patients with chronic schizophrenia not responding adequately to their current antipsychotic medication: results of a potentially pivotal, phase II/III, international, randomized, double blind, placebo-controlled trial (CINP 2024) - No abstract available

Clinical • P2/3 data • CNS Disorders • Psychiatry • Schizophrenia

Remarkable efficacy of evenamide, a glutamate antagonist, as an add-on to antipsychotics in patients with treatment resistant schizophrenia (TRS): results from a one-year, open-label, dose-comparative, randomized, treatment trial (CINP 2024) - No abstract available

Clinical • CNS Disorders • Psychiatry • Schizophrenia

Addition of Evenamide for 1-Year to Antipsychotics in TRS Patients Results in Increasing Clinically Important Benefit to an Extent That a Substantial Proportion No Longer Meet International Criteria for Treatment Resistance (SIRS 2024) - "The 161 TRS patients randomized to treatment tolerated the study medication very well with a high completion rate at 1 year (~75% at 1-year) and low ADO rate (1.9%). During the 1-year treatment period, ~50% of the patients achieved a clinically meaningful benefit (>=20% improvement on PANSS total score): of the patients who achieved this clinically important reduction, ~40% preserved this benefit for at least 12 weeks according to TRRIP criteria. Remarkably, ~50% of the patients no longer met the operational severity criteria used to diagnose TRS at baseline, therefore converting patients into a responsive state."

Clinical • CNS Disorders • Schizophrenia

Add On Treatment With Evenamide in Schizophrenic Patients Not Responding Adequately to Their Current Antipsychotic: Results of a Potentially Pivotal, Phase 2/3, International, Randomized, Double Blind, Placebo-Controlled Trial (SIRS 2024) - "The most common background APs are risperidone (∼40%), olanzapine (∼20%), and clozapine (∼15%); mean duration of treatment with current AP is >1-year. Approximately 430 patients have been screened and ∼270 patients have been randomized to evenamide or placebo to date. The low attrition rate (<4%) during the randomized treatment period and high compliance to the study medication and procedures suggest that evenamide is well tolerated. Routine interim safety analyses reviewed by an ISMB did not detect any evidence of toxicity."

Clinical • P2/3 data • CNS Disorders • Schizophrenia

Design of a Potentially Pivotal, Phase 3, International, Randomized, Double-Blind, Placebo-Controlled Clinical Trial Evaluating Evenamide as Add-On Treatment for Treatment-Resistant Schizophrenia (TRS) Patients (SIRS 2024) - "The results of the study will demonstrate if evenamide, a selective modulator of excessive glutamate release, can benefit TRS patients receiving adjunctive APs, thus confirming the benefit seen in the 1-year pilot study. Positive results from this phase 3 study could change the current management of TRS patients, demonstrating the effectiveness of glutamate modulation as a new therapeutic strategy for this condition."

Clinical • P3 data • CNS Disorders • Schizophrenia

Glutamate Modulation by Evenamide as an Add-On to TRS Patients Not Responding to Their Current Antipsychotics is Associated With Clinically Important Improvement Across Outcome Measures: Results From 1-Year, Open-Label Trial (SIRS 2024) - "[Bortolato et al 2018] A pilot, placebo controlled study in patients with schizophrenia inadequately responding to aripiprazole/risperidone provided a statistically significant signal of efficacy on PANSS positive and CGI-C further supporting its benefits in TRS patients. 161 patients with TRS (males= 69%; mean age= 37.7 year; mean duration of illness= 6.8 year; baseline PANSS= 79.4; CGI-S= 4.5) were randomized, of whom 153 completed 6 weeks of treatment, and 144 of these patients continued into 46 week extension with 85% of them completing 1 year of treatment. [Anand et al 2023] At week 6, the PANSS mean change from baseline was -11.9% improving to -20% at 1 year. The proportion of patients with a clinically meaningful improvement in symptoms (PANSS ≥20% [Meltzer et al 2008; Rosenheck et al 1997]) doubled from 6 week (15.4%) to 6 month (34.0%) and increased further at 1 year (41.8%) with the vast majority (~90%) of the patients who met this level of improvement..."

Clinical • CNS Disorders • Schizophrenia

Treatment With Evenamide for 1 Year in TRS Patients Not Benefitting to Current Antipsychotics is Associated With Sustained, Clinically Important Benefit: Results From a Prospective, Pilot, 1 Year, Randomized, Open-Label Trial (SIRS 2024) - "Evenamide was evaluated as monotherapy or add-on to APs in animal models in which pre-pulse inhibition was impaired using amphetamine, scopolamine, phencyclidine, MK-801, ketamine, or sleep deprivation... This is the first international 1-year trial of evenamide add-on to any AP (except clozapine) in patients with TRS. Scheduled review of safety data by an ISMB did not detect any pattern of motor or CNS symptoms, weight gain, sexual dysfunction or laboratory/EKG abnormalities, indicating the good tolerability of evenamide at all doses in addition to low incidence of ADOs (1.9%). Furthermore, the attrition rate was extremely low (~25% at 1-year) in contrast to published TRS studies (Homman et al., 2021). After 1 year of treatment, the overall improvement in symptoms from baseline was -20% (PANSS total), with a clinically important benefit in the positive subscale (-26%)."

Clinical • CNS Disorders • Schizophrenia

Evenamide: a potential pharmacotherapeutic alternative for treatment-resistant schizophrenia. (PubMed, Int J Neuropsychopharmacol) - No abstract available

Journal • CNS Disorders • Psychiatry • Schizophrenia

Newron to Present Three Posters on Its Clinical Program Evaluating Evenamide in the Treatment of Schizophrenia at the 36th European College of Neuropsychopharmacology Congress (Businesswire) - "Newron Pharmaceuticals S.p.A...announced that it will present three posters at the upcoming 36th European College of Neuropsychopharmacology (ECNP) Congress taking place October 7-10, 2023, at the Centre Convencions Internacional de Barcelona (CCIB) in Barcelona, Spain. Full results from all 161 patients who were randomized in study 014 and who completed six months of participation in study 015 will be presented....Newron presented the data from all 161 patients at the six-week time point and data from the first 100 patients randomized in study 014 who completed one-year of participation in these studies at the 34th CINP World Congress of Neuropsychopharmacology and at the 2023 SIRS Annual Congress in May 2023."

P2 data • CNS Disorders • Schizophrenia

Evenamide, as an add-on to antipsychotics, benefits patients with treatment resistant schizophrenia: 6-month results from an ongoing international randomised study (ECNP 2023) - "Evenamide, a selective inhibitor of voltage-gated sodium channels, is devoid of biological activity at >130 CNS targets, normalizes glutamate release without affecting basal levels, and demonstrated benefits in animal models of psychosis as monotherapy and as an add on to APs (including clozapine), reversing deficits produced by amphetamine, scopolamine, phencyclidine, or ketamine. Discussion This is the first international trial of evenamide used as an add-on to a single typical or atypical AP in patients with TRS. Preliminary, encouraging results of this study have expedited the conduct of a randomized, double-blind, placebo-controlled, 1-year, international study to assess efficacy and safety of two doses (15 and 30 mg bid) of evenamide as add-on treatment in TRS patients not benefiting from their current AP"

Clinical • CNS Disorders • Psychiatry • Schizophrenia

Evenamide as add-on treatment for treatment-resistant schizophrenia patients not benefiting from antipsychotics: design of an international potentially pivotal clinical trial (ECNP 2023) - "Combination of ineffective doses of evenamide and 5HT2/D2 blockers APs, was associated with benefit in animal models of psychosis, suggesting synergies in mechanisms that benefit poor responders to current APs, including clozapine. Results The results of the study will demonstrate if addition of evenamide to patients with TRS on APs is associated with efficacy and tolerability. Conclusions Results from this study will determine if glutamate modulation by evenamide may represent a new therapeutic strategy for the treatment of patients with TRS."

Clinical • CNS Disorders • Psychiatry • Schizophrenia

Evenamide, add-on to antipsychotics, benefits patients with treatment-resistant schizophrenia: final dose-wise results from a Pilot, Phase II, multinational, randomized study (ECNP 2023) - "Evenamide, a selective inhibitor of voltage-gated sodium channels, devoid of activity at >130 CNS targets, normalizes glutamate release without affecting basal glutamate levels, and demonstrates benefits in animal models of psychosis as monotherapy and add on to APs, reversing deficits produced by amphetamine, scopolamine, phencyclidine, or ketamine. Combination of ineffective doses of evenamide and other APs, including clozapine, is associated with similar benefits, suggesting synergies in mechanisms that may benefit poor responders to current APs...Discussion This is the first international trial of a drug acting on the glutamate system as an add-on to a single typical or atypical AP in patients with TRS. Positive results from this study have expedited the design of an international, Phase 3, double-blind, placebo-controlled study of evenamide as add-on to APs in patients with TRS."

Clinical • P2 data • CNS Disorders • Psychiatry • Schizophrenia

Significant And Clinically Important Efficacy Of Evenamide Add - on To An Antipsychotic In Trs Patients Treated For 1 - year In A Phase 2 Study (CINP 2023) - "Evenamide, a selective inhibitor of voltage-gated sodium channels, is devoid of biological activity at >130 CNS targets, normalizes glutamate release without affecting basal levels, and demonstrated benefits in animal models of psychosis as monotherapy and as an add on to APs, reversing deficits produced by amphetamine, scopolamine, phencyclidine, or ketamine. Study 014, with its long-term extension, is the first international trial of a drug acting on the glutamate system as an add-on to APs in patients with TRS. Confirmation of these results in a phase III, double-blind, placebo-controlled study would support the safety and efficacy of evenamide in patients with TRS."

Clinical • P2 data • CNS Disorders • Psychiatry • Schizophrenia

Evenamide Added On To Antipsychotics In Patients With TRS Is Associated With Significant Efficacy: Results From A Pilot, 6 - week, Phase 2 Study (CINP 2023) - "Evenamide, a selective inhibitor of voltage-gated sodium channels, devoid of activity at >130 CNS targets, normalizes glutamate release without affecting basal glutamate levels, and demonstrates benefits in animal models of psychosis as monotherapy and add on to APs, reversing deficits produced by amphetamine, scopolamine, phencyclidine, or ketamine. The pattern of improvement across all efficacy measures in this trial in TRS patients is very encouraging and will lead to the conduct of an international, Phase 3, randomized, double- blind, placebo-controlled study to confirm these benefits of evenamide as an add-on treatment to APs."

Clinical • P2 data • CNS Disorders • Psychiatry • Schizophrenia

Characteristics Of Early And Late Responders To Evenamide Add - on In TRS Patients Not Responding To An Antipsychotic: Results From A Phase 2 Study (CINP 2023) - "The responder definition proposed by Kane et al [1] in monotherapy studies in patients with treatment- resistant-schizophrenia (TRS) has also not been met by any AP other than clozapine. Determining characteristics of early vs late responders may help in reducing attrition in studies in TRS patients who have a longer time to response."

Clinical • P2 data • CNS Disorders • Psychiatry • Schizophrenia

Phase 2 results indicate evenamide, a selective modulator of glutamate release, is associated with remarkable clinically important long-term efficacy when added to an antipsychotic in patients with treatment-resistant schizophrenia (TRS). (PubMed, Int J Neuropsychopharmacol) - No abstract available

Journal • P2 data • CNS Disorders • Psychiatry • Schizophrenia

Newron Presents Exciting New Data From Study 014/015 at CINP World Congress of Neuropsychopharmacology and the 2023 Congress of the Schizophrenia International Research Society (SIRS) (Businesswire) - P2 | N=138 | NCT04461119 | Sponsor: Newron Pharmaceuticals SPA | "presented substantial additional data from its study 014/015 at the 34th CINP World Congress of Neuropsychopharmacology from 7-10 May 2023 in Montreal, Québec, Canada, and the 2023 Congress of the Schizophrenia International Research Society (SIRS) from 11-15 May 2023 in Toronto, Ontario, Canada. Study 014/015 is an international, randomized, open label, rater-blinded study of evenamide as an add-on to an antipsychotic (excluding clozapine) in patients with moderate to severe treatment-resistant schizophrenia (TRS) not responding to their current antipsychotic medication....Efficacy results based on changes from baseline in the PANSS, the Clinical Global Impression of Severity (CGI-S) as well as the Strauss Carpenter Levels of Functioning (LOF) showed a statistically significant improvement at 12 months (p-value < 0.001: paired t-test, LOCF)."

P2 data • CNS Disorders • Schizophrenia

Newron to Present at the 34th CINP World Congress of Neuropsychopharmacology and the 2023 Congress of the Schizophrenia International Research Society (SIRS) (Businesswire) - "Further data from study 014/015 of evenamide in treatment-resistant schizophrenia (TRS) confirms potentially relevant role of glutamatergic release modification when added to TRS patients not responding to marketed...A total of six posters will be presented at the upcoming conferences, including: Results from all 161 patients at the 6-week primary endpoint of Study 014. Full data from the one-year interim timepoint from the cohort of the first 100 patients in study 014/015. Evidence for sustained multidimensional benefits in patients with TRS by combining evenamide’s glutamate release modification with dopamine/serotonin inhibition of current antipsychotics. Characteristics of early and late responders in patients with treatment-resistant schizophrenia."

Clinical data • CNS Disorders • Schizophrenia

Addition of evenamide, a Glutamate Release inhibitor, to Patients with Treatment Resistant Schizophrenia Already on an Antipsychotic is Effective and Associated with Long-Term efficacy: Results of a Phase 2 Study (SIRS 2023) - "In animal models of psychosis, evenamide, both as monotherapy and as an add-on to APs, attenuates deficits produced by amphetamine + chlordiazepoxide, scopolamine, phencyclidine, or ketamine. The very high completion rate in the initial study and at 6 months suggests that evenamide is not only very well tolerated but also found to be effective by patients, caregivers and investigators. Keywords Keywords Resistant treatment schizophrenia Clinical trial Long-term outcomes Glutamate hypothesis Phase II clinical trial Co-author * Presenting Author First Name Last Name Affiliation Ravi * Anand * Anand Pharma Consulting Richard D Hartman NeurWrite LLC Rodolfo Giuliani Newron Pharmaceuticals SpA Alessio Turolla Newron Pharmaceuticals SpA Giovanni Chinellato Newron Pharmaceuticals SpA"

Clinical • P2 data • CNS Disorders • Schizophrenia