Study 014/015 is a Phase II trial evaluating evenamide as add-on therapy for patients with treatment-resistant schizophrenia (TRS)
Full data from first 100 patients at the one-year interim timepoint confirm significant and clinically important, sustained and gradually increasing efficacy on PANSS total, CGI-S and LOF:
41 % of patients were much or very much improved (CGI-C)
29 % of patients showed improvement by 2 or 3 categories (CGI-S), compared to baseline
38% of patients qualified as “super-responders”
PANSS total responders (> 20 % reduction compared to baseline) maintained their response
Final efficacy and safety results from all 161 patients at the six-week primary endpoint of Study 014 confirmed interim results and demonstrated improvement on all PANSS subscales, including negative symptoms
Results from this first international trial of an antipsychotic new chemical entity (NCE) as an add-on to a single antipsychotic in patients with TRS:
support movement to potentially pivotal, multinational, randomized, placebo-controlled trial
suggest a potential new strategy for the management of TRS patients
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), 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.
The study showed that the addition of evenamide to antipsychotics was well tolerated, with low incidence of treatment-emergent adverse events. 97% of patients completed six weeks of treatment, and more than 90% of the completers chose to continue with evenamide treatment into the long-term extension study (study 015).
Final efficacy and safety results from all 161 patients at the six-week primary endpoint of Study 014 were announced in March 2023. Further data covering the improvement observed in all Positive and Negative Syndrome Scale (PANSS) subscales at six weeks, including negative symptoms, was presented at the CINP and SIRS Congresses.
Top-line one-year results from the first 100 patients in Study 014/015 were announced in February 2023 and showed a significant, clinically important and sustained improvement in symptoms, with a gradually increasing effect. Several posters were presented at the CINP and SIRS Congresses detailing the full results from this patient group.
Key findings and conclusions at twelve months:
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). All efficacy scales showed gradual and sustained improvement during the same period
Increasing reduction in the PANSS total score was noted at all time-points compared to baseline; the PANSS responder rate (> 20% improvement) at 12 months was 47%, almost 3 three times the rate at week six (16%)
Ratings of the Clinical Global Impression of Change (CGI-C) indicated that 41% of the patients were rated as ‘much’ or ‘very much’ improved, versus baseline
The CGI-S improved (i.e. the disease severity was considered reduced) by 1.1 units from baseline. Importantly, 29% of patients experienced a two or three category improvement over baseline
38% of patients qualified as “super-responders”, experiencing:
A PANSS total score improvement of at least 20% and
a CGI-C of at least much improved and
a CGI-S of at least 1 point improvement and
a CGI-S of at most mildly ill
The proportion of patients considered as “super-responders” increased 2.5-fold from six weeks to one year
Patients who responded were more likely to complete the one-year treatment period than non-responders
Ravi Anand, Newron’s Chief Medical Officer, said: “The results of study 014/015 presented at both the CINP and SIRS Congresses fully vindicate our extensive preclinical experiments, which indicated the benefits of adding evenamide to antipsychotics that were not efficacious in models of treatment resistance. The multi-modal-benefits observed across various domains with evenamide also validate extensive academic research, suggesting that TRS results from excessive glutamate signalling. Moreover, the gradual and continuous improvement in symptoms over time is unique to treatment with evenamide. We plan to initiate Study 003, a potentially pivotal, multinational, randomized, placebo-controlled trial in patients with TRS later this year and are confident that the results from that study will support the need for re-evaluation of the current therapeutic strategy for managing patients with TRS.”
All posters presented are available at Newron’s website.
About treatment-resistant schizophrenia (TRS)
A significant proportion of patients with schizophrenia show virtually no beneficial response to antipsychotics (APs) despite adequate treatment, leading to a diagnosis of treatment-resistant schizophrenia (TRS). TRS is defined as no, or inadequate, symptomatic relief despite treatment with therapeutic doses of two APs from two different chemical classes for an adequate period. About 15% of patients develop TRS from illness onset, and about one-third of patients overall. Increasing evidence supports abnormalities in glutamate neurotransmission in TRS, not targeted by current APs, along with normal dopaminergic synthesis, to explain the lack of benefit of most typical and atypical antipsychotics.
About study 014/015
Study 014 is a six-week, randomized, rater-blinded study being conducted at multiple sites in three countries (India, Italy and Sri Lanka). Study 014 has completed the enrollment of 161 patients with TRS on a stable, therapeutic dose of a single antipsychotic other than clozapine. The primary objective of the study is to evaluate the safety and tolerability of evenamide given orally at three fixed doses (7.5, 15 and 30 mg bid). The assessment of preliminary efficacy is based on changes from baseline in the Positive and Negative Syndrome Scale (PANSS). Changes from baseline in Clinical Global Impression of Change (CGI-C), Severity of Illness (CGI-S), and Strauss-Carpenter Level of Functioning (LOF) scale, are secondary objectives. Study 015 is the extension study to determine the long-term benefits of glutamate release inhibition. Seventy-seven (77) of the first 100 patients completed the 1-year of treatment with evenamide, 16 discontinued the study early, two due to adverse events (one patient due to fever, vomiting, and nausea, the other due to somnolence, reduced concentration and increased sweating), the other 14 due to withdrawal of consent or lost to follow up.
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:
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. All statements, other than historical facts, contained herein regarding Newron's strategy, goals, plans, future financial position, projected revenues and costs and prospects are forward-looking statements. By their very nature, such statements and assumptions involve inherent risks and uncertainties, both general and specific, and risks exist that predictions, forecasts, projections and other outcomes described, assumed or implied therein will not be achieved. Future events and actual results could differ materially from those set out in, contemplated by or underlying the forward-looking statements due to a number of important factors. These factors include (without limitation) (1) uncertainties in the discovery, development or marketing of products, including without limitation difficulties in enrolling clinical trials, negative results of clinical trials or research projects or unexpected side effects, (2) delay or inability in obtaining regulatory approvals or bringing products to market, (3) future market acceptance of products, (4) loss of or inability to obtain adequate protection for intellectual property rights, (5) inability to raise additional funds, (6) success of existing and entry into future collaborations and licensing agreements, (7) litigation, (8) loss of key executive or other employees, (9) adverse publicity and news coverage, and (10) competition, regulatory, legislative and judicial developments or changes in market and/or overall economic conditions. Newron may not actually achieve the plans, intentions or expectations disclosed in forward-looking statements and assumptions underlying any such statements may prove wrong. Investors should therefore not place undue reliance on them. There can be no assurance that actual results of Newron's research programs, development activities, commercialization plans, collaborations and operations will not differ materially from the expectations set out in such forward-looking statements or underlying assumptions. Newron does not undertake any obligation to publicly update or revise forward-looking statements except as may be required by applicable regulations of the SIX Swiss Exchange where the shares of Newron are listed. This document does not contain or constitute an offer or invitation to purchase or subscribe for any securities of Newron and no part of it shall form the basis of or be relied upon in connection with any contract or commitment whatsoever.