Clozapine

Italian biotech Newron Pharmaceuticals is trying to bring forward the first schizophrenia treatment in decades with evenamide, which could be combined with standard of care like clozapine for patients with chronic disease who do not respond to other treatments. Newron Pharmaceuticals’ add-on schizophrenia treatment improved both positive and negative symptoms as well as severity in patients with the disorder during a phase 2/3 study. The Italian biotech is trying to bring forward the first schizophrenia treatment in decades with evenamide, which could be combined with standard of care like clozapine for patients with chronic disease who do not respond to other treatments. The trial met the main goal of showing improvement on a scale of positive and negative schizophrenia symptoms called the Positive and Negative Syndrome Scale (PANSS), according to a Tuesday release. Positive symptoms include delusions, hallucinations, excitement and grandiosity, while negative symptoms are emotional and social withdrawal, difficulty in abstract thinking and blunted affect. Patients who took evenamide also saw an improvement in the severity of their condition, which was a key secondary endpoint. The four-week Study 008A was conducted at 45 centers in 11 countries, with 291 patients receiving either the study drug or placebo in addition to their current antipsychotic therapy. Three patients discontinued due to adverse events, including two who were on evenamide and one on placebo who died during the trial. Overall, there were no safety flags discovered during the trial and no difference between the rate of central nervous system, gastrointestinal or other adverse events in the evenamide or placebo groups. Newron called the main endpoint results “highly statistically significant,” with patients on evenamide seeing a 10.2-point reduction on the PANSS scale at Day 29, compared to 7.6 for the placebo group. Shares of Newron rose 11% on the Swiss markets to 8.50 Swiss francs ($9.29), compared to 7.64 Swiss francs ($8.35), as of 2:59 p.m. CEST (8:59 a.m. ET). Last year, Newron reported that the effect of evenamide increased between six months and one year. After one year, the biotech reported a more than 50% increase in the six-week change on the PANSS symptom scale. A 30% change was seen after six months. Newron plans to disclose more from the study in the coming weeks. The company also hopes to use the data to make the case for a "potentially pivotal" phase 3 trial testing evenamide over one year in patients with treatment-resistant schizophrenia. 

Ad hoc announcement pursuant to Art. 53 LR Primary endpoint and key secondary endpoint of study met; drug was well tolerated, with no safety concerns identified Glutamatergic inhibition mechanism of action offers an innovative therapeutic option to schizophrenia patients not benefitting from current antipsychotic treatments Next step: Potentially pivotal, Phase III, one-year, randomized, double-blind, placebo-controlled trial in treatment resistant schizophrenia (TRS) International conference call today at 3:00 PM CET/9:00 AM ET MILAN--(BUSINESS WIRE)-- Newron Pharmaceuticals S.p.A. (“Newron”) (SIX: NWRN, XETRA: NP5), a biopharmaceutical company focused on the development of novel therapies for patients with diseases of the central and peripheral nervous system (CNS), today announced positive top-line results from its potentially pivotal study 008A, evaluating the safety, tolerability and efficacy of evenamide (30 mg bid) in patients with chronic schizophrenia currently being treated with a second-generation antipsychotic including clozapine, but demonstrating an inadequate response to that treatment. The study met its primary endpoint of improvement on the Positive and Negative Syndrome Scale (PANSS) Total Score as well as the key secondary endpoint of improvement of the Clinical Global Impression of Severity (CGI-S). Study 008A was a four-week, international, randomized, double-blind and placebo-controlled add-on Phase II/III study performed in 45 centers in 11 countries in Europe, Asia and Latin America. 291 patients were randomized to treatment either with evenamide or placebo as add-on to their current antipsychotic therapy. Evenamide confirmed its favourable safety and tolerability profile, with a high rate of completion. Two hundred and eighty of the 291 patients completed the study with only three patients discontinuing the study due to adverse events, two of them on evenamide and one patient on placebo who died during the study. No new or specific concerns were raised in the study; only 25% of the patients in the study experienced at least one adverse event (evenamide 25% versus placebo 25.8%). There was no difference in the incidence of CNS, psychiatric, gastrointestinal or other adverse events between evenamide and placebo. The most common adverse events reported in patients treated with evenamide were headache, vomiting and nasopharyngitis (three patients, each); similar numbers of patients on placebo experienced these adverse events. In the study, the addition of 30 mg (bid) of evenamide to the patients’ current antipsychotic medication was associated with a highly statistically significant (p-value 0.006) reduction in the PANSS Total Score of 10.2 points, compared to 7.6 points in patients treated with placebo at day 29; the least square mean difference (LS mean difference) was 2.5. For the key secondary measure, the Clinical Global Impression of Severity (CGI-S), the LS mean difference between patients treated with evenamide and placebo was 0.16; the corresponding p-value was 0.037. Ravi Anand, MD, Chief Medical Officer of Newron, stated: “The results seen in study 008A with evenamide are ground-breaking and unique from many perspectives. This is the first major international study to demonstrate the significant benefit of adding a new chemical entity (NCE) to poorly responding, compliant schizophrenia patients being treated with a second-generation antipsychotic. It is also the first demonstration of efficacy in a placebo-controlled trial of a NCE acting exclusively through glutamatergic inhibition. These results, together with the recently reported one-year efficacy results in treatment-resistant patients, substantiate the pivotal role of glutamate in finding new therapeutic options for schizophrenia patients.” Additional details from the study will be disclosed in the coming weeks. Media/analyst/investor Conference Call today at 3 pm CET Newron’s management team will be available today to discuss the top-line results from study 008A. Please dial in five to ten minutes prior to the beginning of the call using one of the following telephone numbers: Switzerland/Europe: +41 (0)58 310 50 00 Germany: +49 (0)69 505 0 0082 United Kingdom: +44 (0)207 107 0613 United States: +1 (1)631 570 5613 Japan: +81 35 050 5361 About evenamide Evenamide, an orally available new chemical entity, specifically blocks voltage-gated sodium channels (VGSCs) and is devoid of biological activity at >130 other CNS targets. It normalizes glutamate release induced by aberrant sodium channel activity (veratridine-stimulated), without affecting basal glutamate levels, due to inhibition of VGSCs. Combinations of ineffective doses of evenamide and other APs, including clozapine, were associated with benefit in animal models of psychosis, suggesting synergies in mechanisms that may provide benefit in patients who are poor responders to current APs, including clozapine. About Newron Pharmaceuticals Newron (SIX: NWRN, XETRA: NP5) is a biopharmaceutical company focused on the development of novel therapies for patients with diseases of the central and peripheral nervous system. The Company is headquartered in Bresso near Milan, Italy. Xadago®/safinamide has received marketing authorization for the treatment of Parkinson’s disease in the European Union, Switzerland, the UK, the USA, Australia, Canada, Latin America, Israel, the United Arab Emirates, Japan and South Korea, and is commercialized by Newron’s Partner Zambon. Supernus Pharmaceuticals holds the commercialization rights in the USA. Meiji Seika has the rights to develop and commercialize the compound in Japan and other key Asian territories. Newron is also developing evenamide as the potential first add-on therapy for the treatment of patients with symptoms of schizophrenia. For more information, please visit: Important Notices This document contains forward-looking statements, including (without limitation) about (1) Newron’s ability to develop and expand its business, successfully complete development of its current product candidates, the timing of commencement of various clinical trials and receipt of data and current and future collaborations for the development and commercialization of its product candidates, (2) the market for drugs to treat CNS diseases and pain conditions, (3) Newron’s financial resources, and (4) assumptions underlying any such statements. In some cases, these statements and assumptions can be identified by the fact that they use words such as “will”, “anticipate”, “estimate”, “expect”, “project”, “intend”, “plan”, “believe”, “target”, and other words and terms of similar meaning. 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View source version on businesswire.com: Contacts For more information, please contact: Newron Stefan Weber – CEO +39 02 6103 46 26 pr@newron.com UK/Europe Simon Conway / Ciara Martin / Natalie Garland-Collins, FTI Consulting +44 20 3727 1000 SCnewron@fticonsulting.com Switzerland Valentin Handschin, IRF +41 43 244 81 54 handschin@irf-reputation.ch Germany/Europe Anne Hennecke / Caroline Bergmann, MC Services +49 211 52925222 newron@mc-services.eu USA Paul Sagan, LaVoieHealthScience +1 617 374 8800, Ext. 112 psagan@lavoiehealthscience.com Source: Newron Pharmaceuticals S.p.A. View this news release online at: