Complete Response Letter from FDA for NDA for roluperidone for the treatment of negative symptoms in patients with schizophrenia

In the CRL the FDA cited the following clinical deficiencies: i. Although one study (MIN-101C03) demonstrated statistical significance on the primary efficacy endpoint, it is insufficient on its own to establish substantial evidence of effectiveness. ii. The NDA submission lacks data on concomitant antipsychotic administration. iii. The NDA submission lacks data needed to establish that the change in negative symptoms of schizophrenia with roluperidone treatment was clinically meaningful. iv. The submitted safety database included an inadequate number of subjects exposed to roluperidone at the proposed dose (64 mg) for at least 12 months.

To address these deficiencies, the FDA stated that Minerva must submit at least one additional positive, adequate, and well-controlled study to support the safety and effectiveness of roluperidone for the treatment of negative symptoms. Minerva must also provide additional data to demonstrate the safety and efficacy of roluperidone co-administered with antipsychotic medications, to support that observed effect on negative symptoms with roluperidone treatment corresponds to a clinically meaningful change, and to demonstrate the long-term safety of the proposed dose. In addition to the clinical deficiencies described above, the FDA also provided comments on, among other items, clinical pharmacology, product quality, biopharmaceutics, and nonclinical issues.

“We are disappointed that the FDA has not approved roluperidone and will request a meeting to discuss the issues raised and attempt to address FDA’s feedback,” said Dr. Remy Luthringer, Executive Chairman and Chief Executive Officer of Minerva. “There is a critical need for a treatment for the negative symptoms of schizophrenia. We believe that roluperidone is a safe and effective therapy for negative symptoms of schizophrenia and we will review FDA’s feedback and consider our potential paths forward, including continuing to work closely with the FDA and providing any additional information as needed, with the goal of bringing this much needed therapy to patients and physicians.”