Minerva Neurosciences faces a significant regulatory hurdle as the FDA has confirmed the requirement for an additional confirmatory clinical trial for roluperidone, the company's investigational treatment for negative symptoms of schizophrenia. The decision follows multiple interactions with the FDA after the company received a Complete Response Letter (CRL) for its New Drug Application in February 2024.
FDA Outlines Confirmatory Trial Requirements
The FDA has specified detailed parameters for the required confirmatory study, which must mirror the design of Minerva's two previous studies (C03 and C07). The trial will enroll patients diagnosed with schizophrenia who present with impairing negative symptoms and stable positive symptoms, with patients selected based on these criteria being stable for six months prior to trial entry.
The study design calls for a double-blinded, placebo-controlled trial where patients receive either a single daily 64 mg dose of roluperidone or placebo as monotherapy. The primary endpoint will measure the change from baseline in PANSS Marder negative symptoms factor score (NSFS) at 12 weeks of treatment compared to placebo.
Critically, the FDA has advised that to support a monotherapy indication, the trial must assess relapses on an observational basis for at least 52 weeks in patients treated with roluperidone monotherapy, placebo, or antipsychotics. The agency stated it would consider NDA resubmission that includes a double-blind, placebo- or active-controlled trial with a duration of at least 52 weeks.
Secondary Endpoints and Trial Measures
The trial's potential key secondary endpoint will compare changes from baseline in the Personal and Social Performance scale total score (PSP) to Week 12, which assesses patients' social functioning. Additional measures will include changes from baseline in Clinical Global Impression of Severity (CGI-S), NSFS, PSP, and CGI-S at earlier timepoints, along with safety and tolerability assessments.
Minerva has agreed with the FDA that best efforts will be made to secure 25-30% of patients from the United States, subject to competitive recruitment. The FDA has confirmed that an adjunctive trial with antipsychotics would not be required for NDA resubmission if Minerva can provide robust, controlled data demonstrating the efficacy and safety of long-term monotherapy with roluperidone in subjects with negative symptoms of schizophrenia.
Financial Pressures Drive Strategic Review
The confirmatory study requirement comes at a challenging time for Minerva's finances. The company reported cash, cash equivalents, and restricted cash of approximately $15.3 million at June 30, 2025, down from $21.5 million at December 31, 2024. Research and development expenses decreased significantly to $1.3 million for the three months ended June 30, 2025, compared to $3.9 million in the same period of 2024.
Net loss for the six months ended June 30, 2025, was $7.0 million, or $0.93 per share, compared to $16.8 million, or $2.22 per share, for the same period in 2024. The improved loss profile reflects lower R&D expenses primarily due to reduced costs associated with drug substance validation campaigns and lower consultant fees.
Strategic Alternatives Under Consideration
As a result of the confirmatory study requirement and current cash position, Minerva has initiated a review process to explore strategic alternatives to maximize value for stockholders. The company is also taking additional steps to reduce costs while conducting this strategic review.
Minerva has cautioned that there can be no assurance the exploration of strategic alternatives will result in any agreements or transactions, or regarding the timing of any such developments. The company does not intend to discuss further developments unless its board of directors approves a definitive action or determines that disclosure is appropriate or required by law.
The strategic review represents a critical juncture for the clinical-stage biopharmaceutical company, which has focused its development efforts on treating central nervous system disorders, with roluperidone as its lead candidate for addressing the significant unmet need in treating negative symptoms of schizophrenia.
