Minerva Neurosciences Announces Study Results Demonstrating Bioequivalence of Phase 2b, Phase 3, & Planned Commercial Formulations of Roluperidone for Treatment of Negative Symptoms of Schizophrenia
Minerva Neurosciences, Inc. recently announced results from a pivotal bioequivalence study comparing the roluperidone formulations used in its late-stage Phase 2b and Phase 3 trials, and the planned commercial formulation. The study met all key pharmacokinetic (PK) objectives and the data demonstrate bioequivalence across the various formulations.
“The results demonstrate bioequivalence in terms of exposure between the formulations used in our two late-stage Phase 2b and Phase 3 efficacy and safety trials with roluperidone and we believe that the data address certain FDA observations following the company’s Type C meeting in November 2020,” said Dr. Remy Luthringer, Executive Chairman and Chief Executive Officer of Minerva. “These results represent important progress along Minerva’s critical path toward submission of an NDA for roluperidone for the treatment of negative symptoms of schizophrenia, for which there are currently no approved treatment options in the US.”
The area under the curve to last detectable concentration (AUClast), the area under the curve extrapolated to infinity (AUCinf), and the maximum plasma concentration (Cmax) are the most commonly used plasma pharmacokinetic parameters to evaluate bioequivalence between various formulations.
For roluperidone, efficacy is mostly driven by plasma exposure of the drug (ie, AUCs) whereas safety margins improve by reducing Cmax of the drug. Furthermore, as roluperidone is intended for chronic use and the assessed formulations are controlled release, AUCinf is the most relevant of the AUCs when single dose data are collected and used for determining bioequivalence.
In this study, the two most important objectives were to establish:
- The comparability under fasted condition of the 64-mg tablet of the Phase 3 formulation of roluperidone compared to the 64-mg dose based on the administration of two 32-mg tablets of roluperidone used in the Phase 2b study, and
- The comparability under fasted condition of a 64-mg tablet of the planned commercial formulation of roluperidone compared to the 64-mg dose based on the administration of two 32-mg tablets of roluperidone used in the Phase 2b study.
The additional two objectives of the study were to establish:
- The comparability under fasted condition of the 64 mg formulation of the planned commercial tablets compared to that used in the Phase 3 for which the results show bioequivalence between the formulations in terms of AUCs and Cmax. and
- The comparability of the 64 mg dose of the commercial formulation under fed condition compared to fasted condition for which the results show bioequivalence of both AUCinf and Cmax between the fed and fasted conditions.
Dr. Luthringer added, “The additional results obtained are significant as they demonstrate the comparability of the formulations used in the late-stage efficacy and safety trials of roluperidone with the planned commercial formulation and allow administration of the drug with or without food. We intend to submit a request to the FDA for a pre-NDA meeting.”
Subject screening in this study was initiated on April 23, 2021, the completion of the enrollment of 48 healthy volunteers was announced on June 29, 2021, and the last subject assessment took place on July 26, 2021. Subjects were randomized to the four treatment sequences described above in a 1:1:1:1 ratio.
Of the 48 subjects randomized, 45 completed all study periods. Male subjects constituted 69% of the participants, and 75% of the subjects were white. Median age was 36 years, and all had negative SARS-CoV2 status at the beginning of the study and of every study period with the exception of 1 subject who tested positive at the beginning of study Period 4 and was discontinued. The mean body mass index was 28.1±4 kg/m2.
Schizophrenia is a chronic, severe and debilitating type of mental illness characterized by distortions in thinking, perception, emotions, language, sense of self and behavior. Schizophrenia affects 20 million people worldwide. Negative symptoms can cause individuals with schizophrenia to withdraw from society, become disinterested or unable to complete tasks or feel pleasure. Negative symptoms are characterized by five constructs: blunted affect, alogia, avolition, anhedonia, and asociality.
Negative symptoms are the main cause of the poor functional outcome of patients suffering from schizophrenia and may also be one of the main reasons ultrahigh risk adolescents may develop full blown schizophrenia. There are currently no treatments approved for negative symptoms of schizophrenia.
Minerva Neurosciences, Inc. (Nasdaq: NERV) is a clinical-stage biopharmaceutical company focused on developing product candidates to treat central nervous system (CNS) diseases. Our goal is to transform the lives of patients with improved therapeutic options. Minerva’s portfolio of compounds includes roluperidone (MIN-101), in clinical development for negative symptoms of schizophrenia, and MIN-301, in pre-clinical development for Parkinson’s disease. For more information, please visit our website.
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