GlobeNewswire by notified

Minerva Neurosciences Announces Results of Dose Escalation Study Evaluating Roluperidone (MIN-101) Administered at Supra-Therapeutic Doses in Healthy Volunteers

Share
  • Findings suggest expanded therapeutic window and significantly improved cardiovascular safety margin compared to formulation used in Phase 2b trial
     
  • All doses tested up to 256 milligrams appear safe and well tolerated with no significant changes in cardiac repolarization and QTc intervals
     
  • Tested formulation is used in ongoing Phase 3 trial
     
  • Data to be reviewed at Minerva’s roluperidone update and key opinion leader event on Tuesday, November 20, 2018 beginning at 8:00 a.m. Eastern Time in New York

WALTHAM, Mass., Nov. 19, 2018 (GLOBE NEWSWIRE) -- Minerva Neurosciences, Inc. (NASDAQ: NERV), a clinical-stage biopharmaceutical company focused on the development of therapies to treat central nervous system (CNS) disorders, today announced the results from a prospective, double-blind, placebo-controlled, randomized single-escalating dose study in healthy subjects to evaluate the investigational drug roluperidone as monotherapy administered at nine ascending doses (16, 32, 64, 96, 128, 160, 192, 224 and 256 milligrams [mg]).  The highest dose tested is 4 multiples of the highest dose (64 mg) being used in the ongoing Phase 3 trial with this compound, under development for the treatment of negative symptoms of schizophrenia. 

The primary objectives of the study included the evaluation of the pharmacokinetics, dose-proportionality and the effect of plasma concentrations of roluperidone and its main metabolites on pharmacodynamic parameters using electrocardiogram (ECG) Fridericia-corrected QT interval (QTcF), a measurement of cardiac function.  Secondary objectives included evaluation of safety and tolerability.  A third objective was to provide an estimate of the supra-therapeutic dose to be used in the thorough QT study planned as part of the New Drug Application (NDA).

The trial included a total of 90 subjects. 72 received 7 different doses of roluperidone, and 18 received placebo. All subjects who were dosed completed the study as planned except for one male subject who received placebo and subsequently withdrew his consent.

Data from this trial demonstrated the following:

  • The pharmacokinetics of roluperidone and its metabolites were dose proportional.

  • No QTcF duration > 480 milliseconds (msec) or increases > 60 msec compared to baseline values were observed in any subject.

  • 160 mg was the only roluperidone dose to show an adjusted QTcF mean increase from baseline of 10.7 msec.  All other doses showed means -1.3 to 5 msec.

  • No significant change in repolarization was observed.

  • Two subjects (11%) in the placebo group and nine subjects (13%) in the roluperidone group reported adverse events that were mild to moderate in severity and resolved without sequelae.

  • Doses up to 160 mg or 2.5 multiples of the highest dose being tested in the ongoing Phase 3 trial had no effect on any cardiac safety parameters.

  • Slight but not clinically relevant increases in heart rate were observed in the placebo group and some of the roluperidone doses.

  • No serious adverse events were reported.

Additional details will be presented at the Company’s roluperidone update and key opinion leader event on Tuesday, November 20, 2018, 8:00 a.m., in New York.  This event will be webcast, and institutional investors and analysts may RSVP to jporcelli@soleburytrout.com.

“We believe these findings suggest an expanded therapeutic window and a significantly improved safety margin for roluperidone,” said Dr. Jay Saoud, Senior Vice President, Head of Research and Development at Minerva.  “They provide further evidence that the formulation being used in the ongoing Phase 3 trial of roluperidone has a significantly reduced maximum concentration (Cmax) of the metabolite known as BFB-520 when compared to the formulation used in the Phase 2b trial, thereby reducing the potential of transient QTc increases at the doses currently tested in that Phase 3 trial.

“Furthermore, we believe these data suggest the potential for future testing of roluperidone in schizophrenic patients with an exacerbation of psychosis at higher doses than those being used in the Phase 3 trial,” said Dr. Saoud.

The Company had previously established the following in a study comparing the Phase 3 formulation and the Phase 2b formulation:

  • Bioequivalent exposures of roluperidone as measured by area under the curve (AUC) for both the Phase 3 and Phase 2b trials (AUC is the main efficacy driver for the drug);

  • Reduction of the Cmax of BFB-520 by approximately 30% in the Phase 3 formulation compared to that used in Phase 2b, thus explaining the increased safety margin reported above;

  • No observations of QTcF prolongations throughout the study;

  • No observable food effect, thus allowing administration of the drug with or without food without changing its pharmacokinetic properties;

  • Confirmation of the overall safety and tolerability profile of roluperidone.

The ongoing Phase 3 trial with roluperidone is a multicenter, randomized, double-blind, parallel-group, placebo-controlled, 12-week study to evaluate the efficacy and safety of 32 mg and 64 mg of roluperidone as monotherapy in adult patients with negative symptoms of schizophrenia.  The 12-week study will be followed by a 40-week, open-label extension period during which patients on drug will continue receiving their original dose and patients on placebo will receive either 32 mg or 64 mg of roluperidone. Approximately 500 patients are expected to be enrolled at approximately 60 clinical sites in the U.S. and Europe.  Top-line results from the 12-week double-blind phase of this trial are expected in mid-2019.

The previously announced Phase 2b trial with roluperidone achieved its primary endpoint, demonstrating a statistically significant benefit of the compound over placebo in improving negative symptoms1 ,[2],[3].  Roluperidone was reported to be well tolerated, and the incidence and types of side effects did not differ significantly between the roluperidone group and the placebo group.  Unlike many currently marketed antipsychotic drugs, no metabolic adverse effects, no weight gain and no extra-pyramidal symptoms were observed.

About Roluperidone

Roluperidone is a drug candidate with equipotent affinities for 5‑hydroxytryptamine-2A (5-HT2A) and sigma2 and at lower affinity levels, α1-adrenergic receptors. Roluperidone exhibits no affinity for dopaminergic, muscarinic, cholinergic and histaminergic receptors.  Roluperidone has no direct dopaminergic post-synaptic blocking effects, known to be involved in some side effects like extrapyramidal symptoms, sedation, prolactin increases and weight gain.

About Minerva Neurosciences:

Minerva Neurosciences, Inc. is a clinical-stage biopharmaceutical company focused on the development and commercialization of a portfolio of product candidates to treat CNS diseases.  Minerva’s proprietary compounds include: roluperidone (MIN-101), in clinical development for schizophrenia; MIN-117, in clinical development for major depressive disorder (MDD); seltorexant (MIN-202 or JNJ-42847922), in clinical development for insomnia and MDD; and MIN-301, in pre-clinical development for Parkinson’s disease.  Minerva’s common stock is listed on the NASDAQ Global Market under the symbol “NERV.”  For more information, please visit www.minervaneurosciences.com

Forward-Looking Safe Harbor Statement

This press release contains forward-looking statements which are subject to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, as amended.  Forward-looking statements are statements that are not historical facts, reflect management’s expectations as of the date of this press release, and involve certain risks and uncertainties.  Forward-looking statements include statements herein with respect to the timing and scope of current clinical trials and results of clinical trials with roluperidone (MIN-101); the timing and scope of future clinical trials and results of clinical trials with roluperidone; the clinical and therapeutic potential of roluperidone; our ability to successfully develop and commercialize our therapeutic products; the sufficiency of our current cash position to fund our operations; and management’s ability to successfully achieve its goals.  These forward-looking statements are based on our current expectations and may differ materially from actual results due to a variety of factors including, without limitation, whether roluperidone will advance further in the clinical trials process and whether and when, if at all, it will receive final approval from the U.S. Food and Drug Administration or equivalent foreign regulatory agencies and for which indications; whether any of our therapeutic products will be successfully marketed if approved; whether any of our therapeutic product discovery and development efforts will be successful; management’s ability to successfully achieve its goals; our ability to raise additional capital to fund our operations on terms acceptable to us; and general economic conditions.  These and other potential risks and uncertainties that could cause actual results to differ from the results predicted are more fully detailed under the caption “Risk Factors” in our filings with the Securities and Exchange Commission, including our Quarterly Report on Form 10-Q for the quarter ended September 30, 2018, filed with the Securities and Exchange Commission on November 5, 2018.  Copies of reports filed with the SEC are posted on our website at www.minervaneurosciences.com.  The forward-looking statements in this press release are based on information available to us as of the date hereof, and we disclaim any obligation to update any forward-looking statements, except as required by law.

Contact:
William B. Boni
VP, Investor Relations/
Corp. Communications
Minerva Neurosciences, Inc.
(617) 600-7376

1 Davidson, M. et al., Efficacy and Safety of MIN-101: A 12-Week Randomized, Double-Blind, Placebo-Controlled Trial of a New Drug in Development for the Treatment of Negative Symptoms in Schizophrenia, 28 July 2017, https://doi.org/10.1176/appi.ajp.2017.17010122
2 Kirkpatrick, B. et al., The brief negative symptom scale (BNSS): Sensitivity to treatment effects, Schizophr. Res. (2017), https://www.ncbi.nlm.nih.gov/pubmed/29275856 3 Keefe, Richard et al., Cognitive effects of MIN-101 in patients with schizophrenia and negative symptoms: results from a randomized controlled trial: https://doi.org/10.4088/JCP.17m11753

To view this piece of content from www.globenewswire.com, please give your consent at the top of this page.

About GlobeNewswire by notified

GlobeNewswire by notified
GlobeNewswire by notified
One Liberty Plaza - 165 Broadway
NY 10006 New York

https://notified.com

GlobeNewswire by notified is one of the world's largest newswire distribution networks, specializing in the delivery of corporate press releases financial disclosures and multimedia content to the media, investment community, individual investors and the general public.

Subscribe to releases from GlobeNewswire by notified

Subscribe to all the latest releases from GlobeNewswire by notified by registering your e-mail address below. You can unsubscribe at any time.

Latest releases from GlobeNewswire by notified

Brookfield Corporation Completes Annual Filings19.3.2024 01:55:08 CET | Press release

BROOKFIELD, NEWS, March 18, 2024 (GLOBE NEWSWIRE) -- Brookfield Corporation (“Brookfield”) (NYSE: BN, TSX: BN) today announced that it has filed its 2023 annual materials on Form 40-F, including its audited financial statements and management’s discussion and analysis for the year ended December 31, 2023, with the SEC on EDGAR as well as with the Canadian securities authorities on SEDAR. These documents are also available at www.brookfield.com and a hardcopy will be provided to shareholders free of charge upon request. About Brookfield Corporation Brookfield Corporation is a leading global investment firm focused on building long-term wealth for institutions and individuals around the world. We have one of the largest pools of discretionary capital globally, which is deployed across our three core businesses – asset management, insurance solutions, and our operating businesses. Through our core businesses, we invest in real assets that form the backbone of the global economy to deliver

Schneider Electric Collaborates with NVIDIA on Designs for AI Data Centers18.3.2024 23:12:33 CET | Press release

• New reference designs will offer a robust framework for implementing NVIDIA’s accelerated computing platform within data centers;• Designs will optimize performance, scalability, and energy efficiency; Schneider Electric, the leader in the digital transformation of energy management and automation, today announced a collaboration with NVIDIA to optimize data center infrastructure and pave the way for groundbreaking advancements in edge artificial intelligence (AI) and digital twin technologies. Schneider Electric will leverage its expertise in data center infrastructure and NVIDIA’s advanced AI technologies to introduce the first publicly available AI data center reference designs. These designs are set to redefine the benchmarks for AI deployment and operation within data center ecosystems, marking a significant milestone in the industry's evolution. With AI applications gaining traction across industries, while also demanding more resources than traditional computing, the need for

Hexagon Purus ASA: Issue of shares under the Company's LTIP plan18.3.2024 21:35:00 CET | Press release

The long term incentive plan of December 2020 (the "2020 LTIP") for Hexagon Purus ASA (the "Company") vested upon approval of the 2023 annual financial statements. Consequently, the Company's board of directors, has resolved to issue in total 909,742 new shares to the entitled employees pursuant to the authorization to issue shares granted on 25 May 2023. Following registration of the share issue, the Company's registered share capital will be NOK 27,770,719.80, divided into 277,709,198 shares, each having a face value of NOK 0.10. 541,242 of the new shares were issues to PDMRs, as further specified in the attached forms. For additional information, please contact: Salman Alam, Chief Financial Officer, Hexagon Purus Telephone: +47 476 12 713 | salman.alam@hexagonpurus.com Mathias Meidell, Investor Relations Director, Hexagon Purus Telephone: +47 909 82 242 | mathias.meidell@hexagonpurus.com About Hexagon Purus: Hexagon Purus enables zero emission mobility for a cleaner energy future. T

Inventiva announces positive results from the Phase II, LEGEND, Proof-of-Concept study combining lanifibranor with empagliflozin in patients with MASH/NASH and T2D18.3.2024 21:00:00 CET | Press release

LEGEND achieved its primary efficacy endpoint by significantly lowering HbA1c level in both the lanifibranor arm and in the lanifibranor with empagliflozin arm compared to placebo.Statistical significance was also achieved on several markers of liver injury, markers of glucose and lipid metabolism, as well as hepatic steatosis.Patients treated with lanifibranor in combination with empagliflozin maintained a stable weight throughout the 24 weeks study, addressing the moderate, metabolically healthy, weight gain that has been observed in some patients treated with lanifibranor.Treatment with lanifibranor alone and in combination with empagliflozin decreased the ratio of visceral abdominal fat to subcutaneous fat, reflecting a shift from pro-inflammatory visceral fat towards metabolically healthy adipose tissue.The treatment with lanifibranor 800mg/once daily alone or in combination with empagliflozin for 24 weeks was well tolerated, with no safety concerns reported.Inventiva will host an

Driving Excellence: C.K. McWhorter Grants Bentley Motors McWhorter Family Trust Warrant of Automotive Distinction18.3.2024 20:56:28 CET | Press release

LONDON, March 18, 2024 (GLOBE NEWSWIRE) -- The McWhorter Family Trust proudly announces its partnership with Bentley Motors, heralding a new era of automotive excellence. In a momentous decision, the Trust bestows upon Bentley Motors the emblem of automotive distinction, recognizing its unwavering commitment to luxury, innovation, and craftsmanship. Incorporating Bentley Motors into the McWhorter Family Trust’s Portfolio: The addition of Bentley Motors to the McWhorter Family Trust’s prestigious portfolio signifies a strategic expansion into the realm of automotive luxury. This pivotal decision underscores the Trust's dedication to investing in brands that epitomize excellence and timeless sophistication. Furthermore, it opens doors to potential indirect investment opportunities in Bentley Motors through avenues such as automotive technology and events. Strategic Investment Approach of C.K. McWhorter: C.K. McWhorter, in orchestrating the structure of a Single Family Office (SFO), strat

HiddenA line styled icon from Orion Icon Library.Eye