Minerva Provides Update on Phase 3 Design and Development Strategy for MIN-101
Advancing a new potential therapeutic paradigm for the treatment of negative symptoms, a key unmet need in schizophrenia and other brain diseases
Company to host conference call on
"We are very excited to be taking MIN-101 into a pivotal Phase 3 trial, which has the potential to identify a new approach to the treatment of schizophrenia and improve the quality of life for millions of patients," said Dr.
Data from the Company's Phase 2b trial with MIN-101 have informed the design of the Phase 3 trial. Key findings from the Phase 2b trial include observations of a direct effect on negative symptoms (rather than an indirect or pseudo effect linked to improvements in other symptoms and/or a different side effect profile). The data also support the durability of this effect through the entire 36-week duration of the trial, which included a 12-week double-blind, placebo-controlled core phase and a 24-week, open-label extension phase. The specificity of MIN-101's therapeutic effects on negative symptoms was validated by the stability of positive symptoms observed over the entire duration of treatment and a side effect profile comparable to placebo, particularly as it relates to extra-pyramidal symptoms (EPS). The Company believes that the unique pharmacological profile of MIN-101 (sigma 2 and serotonin 5HT2a receptor antagonism) and the absence of direct binding to post-synaptic dopamine receptors may explain its specific effects on negative symptoms.
Key elements of the Phase 2b trial that will be incorporated into the Phase 3 trial include:
- improvement in negative symptoms as the primary endpoint;
- monotherapy administration of MIN-101 and no co-administration with atypical antipsychotics at any stage in the study;
- recruitment of patients with moderate-to-severe negative symptoms expressed as a specified minimum threshold baseline score on the Positive and Negative Syndrome Scale (PANSS) negative sub-scale; and
- a 12-week double-blind, randomized, placebo-controlled core phase followed by an open-label extension phase.
Two doses of MIN-101 or placebo will be
administered during the double-blind phase of the Phase 3 trial, which will last 12 weeks, followed by an optional 36-week extension phase in which all patients will receive MIN-101. Approximately 500 patients will be enrolled at approximately 60 clinical sites across the
The primary Phase 3 trial endpoint of improvement in negative symptoms at 12 weeks will be measured by the PANSS negative sub-scale score using the Marder factor, a widely recognized instrument for quantifying severity of negative symptoms. The Marder negative sub-score is similar to the White negative sub-score used in the Phase 2b trial. The two factors differ from each other in that the Marder score has eliminated four items and added one on active social avoidance (G16 item). The Company is employing the Marder scale because this item has been shown to be well correlated with patients' overall functional outcome.
The Company's Phase 3 trial design is intended to replicate the experience of "real world" clinical practice in schizophrenia. Many patients are dissatisfied and not well served by continuous antipsychotic treatment as evidenced by poor compliance with medications. Recent scientific literature points toward the fact that indefinite antipsychotic maintenance treatment in schizophrenic patients (provided by post-synaptic blockade of dopamine receptors) may be responsible for poor long term functional outcomes in addition to well described side effects, including EPS, weight gain, sedation and prolactin increase. In summary, the Phase 3 trial will seek to confirm clinically meaningful effects on patients' negative symptoms and to determine whether patients can stay stable in terms of positive symptoms without experiencing the adverse effects of antipsychotics.
Treatment of the positive symptoms of schizophrenia represents a large market estimated at more than
In Phase 4 development, the Company plans to conduct additional trials to expand the profile of MIN-101. These may potentially include a study comparing the rate of psychosis relapses in patients treated with MIN-101, standard of care with antipsychotics or placebo. In addition, the Company may conduct a trial in adolescents at high risk for schizophrenia who during the prodromal phase manifest negative symptoms.
While negative symptoms are a core component of schizophrenia and predict poor functional capacity, they are not specific to that disease but are also recognized as a hallmark of other diseases. These include neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, mood disorders, schizophrenia spectrum disorders and autism spectrum disorders. The Company plans to assess these indications as expansion options for MIN-101 in a development program beyond the planned Phase 3 study in schizophrenia.
Conference call information
The Company will host a conference call and live webcast tomorrow,
The webcast can be accessed under "Events and Presentations" in the Investors and Media section of Minerva's website beginning approximately two hours after the event for 90 days.
About schizophrenia and the impact of negative symptoms
Schizophrenia remains among the top ten disabling conditions worldwide for young adults and affects more than 21 million people worldwide. According to Datamonitor, an independent market research firm, in 2016 approximately 3.3 million people suffered from schizophrenia in
Although positive psychotic symptoms are characteristic of schizophrenia, negative symptoms constitute one of the main sources of burden of illness, represent an important treatment target and are a major cause of the poor vocational and social capabilities of these patients. These symptoms, which include a-motivation, avolition, lack of initiative, and restricted personal interaction, are associated with poor psychosocial functioning.
In the majority of schizophrenia patients, acute positive symptoms remit due to treatment with antipsychotics (dopamine-blocking drugs) or spontaneously. Antipsychotic drugs also reduce the risk for recurrence of psychosis. However, many patients maintain remission of psychosis without antipsychotic dopamine blocking drugs. Nevertheless, they continue to suffer negative symptoms, for which no
About MIN-101
MIN-101 is a drug candidate with equipotent affinities for sigma2 and 5‑hydroxytryptamine-2A (5-HT2A) and lower affinity at α1-adrenergic receptors. MIN-101 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.
The Phase 2b trial with MIN-101, announced in 2016 and presented at the annual meeting of the
About
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 results of future clinical milestones with MIN-101, including the planned Phase 3 trial of MIN-101, the timing and scope of future clinical trials and results of clinical trials with this compound; the potential for a single Phase 3 trial with supportive Phase 2b results to support
the basis for an NDA; the timing and outcomes of future interactions with
Contact:William B. Boni VP, Investor Relations/ Corp. CommunicationsMinerva Neurosciences, Inc. (617) 600-7376
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