DGAP-News: Newron Pharmaceuticals S.p.A.
/ Key word(s): Study results
01.04.2021 / 07:00
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Newron announces results of explanatory studies with evenamide in healthy volunteers and patients with schizophrenia
Milan, Italy and Morristown, NJ, USA, April 1, 2021 – 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, today announced initial results from two short-term explanatory studies in evenamide: study 010 in healthy volunteers and study 008 in patients with schizophrenia.
Results from study 010, a four-week, single dose, cross-over Thorough QT (TQT) study in 56 healthy volunteers, designed to evaluate the effects of evenamide (30 mg and 60 mg) compared with placebo and moxifloxacin 400 mg on the QT segment specifically, and on the electrocardiogram (ECG) generally, was requested by the US Food and Drug Administration (FDA) and under the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). The results indicate that evenamide was devoid of any QTcF prolongation compared to placebo (indicating lack of any increased risk of arrythmia), while moxifloxacin was associated with a 17.3 ms median maximum increase suggestive of clinically significant risk of arrhythmia. These results strongly suggest that evenamide does not increase a patient’s risk of QTc prolongation and arrhythmias, a risk generally associated with antipsychotics.
Study 008, a four-week, randomized, double-blind placebo-controlled study was designed to primarily evaluate the safety, tolerability, and electroencephalogram (EEG) effects of two fixed doses of evenamide (7.5 mg and 15 mg BID). The study was requested by the FDA to address questions which arose from a study of evenamide in rats, and central nervous system (CNS) events observed following high-dose administration of evenamide in dogs. The study was performed in 138 outpatients with chronic schizophrenia, receiving treatment with a second-generation atypical antipsychotic at study centers in the United States and India.
Over 95% of the patients completed study 008. No patient on evenamide discontinued from the study due to adverse events, and there were no significant adverse events relating to evenamide. No symptoms were observed suggestive of severe CNS events, symptoms/signs of seizures, EEG diagnosis of seizure like activity, or cardiac events in patients with evenamide. There were no differences in laboratory, ECG or vital signs abnormalities between evenamide and placebo-treated patients. The most frequent adverse events observed were related to CNS, gastrointestinal disorders, psychiatric disorders, metabolism and nutrition disorders and laboratory investigations. The most frequent adverse events reported (greater than 5%) were headache and somnolence, which were equally distributed between evenamide and placebo.
Study 008 was designed to primarily assess safety and was not powered to demonstrate efficacy. The results, as expected, indicated that the 7.5 mg BID was a “no-effect” dose, which will not be investigated further. The 15 mg BID dose produced a higher magnitude response on the total PANSS than 7.5 mg BID, but this was not statistically significant when compared to placebo. The safety of the 30 mg BID (designated as the therapeutic dose) will be assessed in a planned additional study 008A in patients with schizophrenia, which is required in order to fully comply with the FDA’s original request prior to starting the planned phase III program. Study 008A will be initiated in the next days, with results expected in the second half of 2021.
Ravi Anand, MD, Newron’s CMO, commented: “The results of study 010 are of far-reaching importance as they indicate that evenamide, even at doses of 60 mg (twice the therapeutic dose), is devoid of any arrhythmic effect and thus can be safely added to any other antipsychotic. Furthermore, the safety data, specifically, the lack of any systemic pattern of adverse effects relating to the CNS (including EEG) indicate that the drug is safe at the doses investigated. We will now evaluate the safety of the 30 mg (BID) dose, the expected therapeutic dose, in patients with schizophrenia, in study 008A and plan for the initiating of our phase III program shortly after.”
The proposed phase III clinical trial program with evenamide targets patients with schizophrenia experiencing worsening of psychosis on atypical antipsychotics, and treatment-resistant patients not responding to clozapine. Clozapine is the only antipsychotic approved worldwide for treatment-resistant schizophrenia. The program will commence once study 008A results are available.
Newron is currently evaluating potential options for partnering/co-developing the further development of evenamide.
Evenamide has the potential to be first add-on therapy for the treatment of patients with positive symptoms of schizophrenia. The compound is an orally available New Chemical Entity that specifically targets voltage-gated sodium channels for the treatment of schizophrenia. Evenamide originates from Newron’s ion channel program and has a unique mechanism of action: glutamate modulation and voltage-gated sodium channel blockade. Evenamide modulates sustained repetitive firing, without inducing impairment of normal neuronal excitability. It normalizes glutamate release induced by aberrant sodium channel activity. In a Phase IIa clinical study, Newron demonstrated evenamide’s evidence of efficacy in significantly improving symptoms of psychosis compared with placebo when added to two of the most commonly prescribed atypical antipsychotics in patients with chronic schizophrenia. The study also indicated that evenamide is devoid of an effect on any of the over 130 neurotransmitters, enzymes, or transporters targeted by most antipsychotics.
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(R)/safinamide has received marketing authorization for the treatment of Parkinson’s disease in the European Union, Switzerland, the USA, Australia, Canada, Brazil, Colombia, 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 positive symptoms of schizophrenia. For more information, please visit: www.newron.com
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