FDA Issues CRL for Roluperidone in the Treatment of Negative Symptoms of Schizophrenia


The CRL cited several areas for clinical improvement necessary for future approval of the treatment.

everything bagel_AdobeStock

everything bagel_AdobeStock

The US Food & Drug Administration (FDA) has issued a Complete Response Letter (CRL) in follow-up to the New Drug Application (NDA) for roluperidone (MIN-101) as a treatment for negative symptoms of schizophrenia. In the CRL, the FDA cited several clinical areas for improvement necessary for future approval of roluperidone.

The cited deficiencies include insufficient data to establish that the change in negative symptoms with roluperidone treatment was clinically meaningful, and a lack of data on concomitant administration of antipsychotic drugs in the NDA submission. The FDA also stated that there was an inadequate number of participants exposed to the proposed dose (64 mg) of roluperidone for at least 12 months in the safety database. Finally, while 1 study—MIN-101C03—showed statistical significance on the primary efficacy endpoint, the FDA concluded that this study alone was insufficient to establish substantial evidence of effectiveness.1

To address these deficiencies, the FDA has mandated roluperidone developer Minerva Neurosciences Inc to submit at least 1 additional positive, adequately controlled study to support the safety and efficacy of roluperidone in the treatment of negative symptoms. Minerva is also required to provide further data demonstrating the safety and efficacy of roluperidone when co-administered with antipsychotic medications and to establish the long-term safety of the proposed dose. Additionally, the FDA provided comments on various aspects including biopharmaceutics, product quality, and clinical pharmacology, as well as nonclinical issues.1

This announcement follows the NDA submission for roluperidone for the treatment of negative symptoms in schizophrenia on May 8, 2023, and Minerva’s formal dispute resolution and appeal of the FDA’s original refuse-to-file letter in October 2022.2

“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 Remy Luthringer, PhD, executive chairman and chief executive officer of Minerva Neurosciences Inc, in a press release. “There is a critical need for a treatment for the negative symptoms of schizophrenia.”

“Treatments for negative symptoms in schizophrenia have remained elusive,” added John J. Miller, MD, in Psychiatric Times®. “The combination of cognitive and negative symptoms contributes greatly to the functional impairment of many patients with schizophrenia. Roluperidone has a unique portfolio of receptor binding affinities with an unclear mechanism of action to explain the possible improvement of negative symptoms in schizophrenia.”2

Miller is Medical Director, Brain Health, Exeter, New Hampshire; Editor in Chief of Psychiatric Times; Staff Psychiatrist at Seacoast Mental Health Center, Exeter; Consulting Psychiatrist, Exeter Hospital, Exeter; and Consulting Psychiatrist, Insight Meditation Society, Barre, Massachusetts.

Luthringer concluded in a press release that, “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.”

Stay up-to-date on news related to research on promising new interventions and developments in the treatment of a wide variety of psychiatric disorders at psychiatrictimes.com.

Note: This article was prepared with the assistance of ChatGPT.


1. Minerva Neurosciences receives Complete Response Letter from FDA for New Drug Application for roluperidone for the treatment of negative symptoms in patients with schizophrenia. Minerva Neurosciences Inc. News release. February 27, 2024. Accessed February 27, 2024. https://www.globenewswire.com/news-release/2024/02/27/2835962/32445/en/Minerva-Neurosciences-Receives-Complete-Response-Letter-from-FDA-for-New-Drug-Application-for-Roluperidone-for-the-Treatment-of-Negative-Symptoms-in-Patients-with-Schizophrenia.html

2. Miller JJ. Medication pipeline: schizophrenia and PTSD. Psychiatric Times. January 11, 2024. Accessed February 26, 2024. https://www.psychiatrictimes.com/view/medication-pipeline-schizophrenia-and-ptsd

Recent Videos
Erin Crown, PA-C, CAQ-Psychiatry, and John M. Kane, MD, experts on schizophrenia
nicotine use
brain schizophrenia
exciting, brain
© 2024 MJH Life Sciences

All rights reserved.