Benzinga | Dec 1, 2020 06:15AM EST

Minerva Neurosciences On Dec 1, Received Official Meeting Minutes From Co.'s Nov 10, Type C Meeting With FDA; Objective Of Meeting Was To Obtain FDA Input Regarding Roluperidone Data Package And Its Readiness To Support NDA Submission

Minerva Neurosciences Announces Outcome of Type C Meeting with FDA and Next Steps in the Development of Roluperidone

Waltham, MA, December 1, 2020 -- Minerva Neurosciences, Inc. (NASDAQ:NERV), a clinical-stage biopharmaceutical company focused on the development of therapies to treat central nervous system (CNS) disorders, today announced that it has received official meeting minutes from the November 10, 2020 Type C meeting with the U.S. Food and Drug Administration (FDA) regarding development of roluperidone for treatment of negative symptoms in schizophrenia.

The objective of this meeting was to obtain FDA input regarding the roluperidone data package and its readiness to support a New Drug Application (NDA) submission. The two main topics addressed during the meeting were:



1.

Readiness for submission of NDA

Minerva requested confirmation from FDA that, based on the totality of evidence, the data from the MIN-101C03 (Phase 2b) and MIN-101C07 (Phase 3) studies constitute substantial evidence of the effectiveness of the 64 milligrams (mg) dose of roluperidone for the treatment of negative symptoms in schizophrenia and would warrant review of an NDA submission.

FDA advised that the Phase 2b study is problematic because it did not use the commercial formulation of roluperidone and was conducted solely outside of the United States. In addition, FDA commented that the Phase 3 study does not appear to be capable of supporting substantial evidence of effectiveness, because neither dose of roluperidone showed a statistically significant separation from placebo at Week 12 in the intent-to-treat (ITT) analysis set. FDA cautioned that an NDA submission based on the current data from the Phase 2b and Phase 3 studies would be highly unlikely to be filed and that, at a minimum, there would be substantial review issues due to the lack of two adequate and well-controlled trials to support efficacy claims for this indication.

FDA acknowledged that the data from the Phase 2b and Phase 3 studies appear to show promising signals and encouraged Minerva to continue the development of roluperidone for treatment of negative symptoms in schizophrenia, which FDA confirmed is an unmet need.

Minerva recognizes FDA's comments but believes they can be addressed based on published regulatory guidance and precedents. The company has comparable pharmacokinetic data for the formulations used in Phase 2b and Phase 3 (the commercial formulation) and intends to perform a pivotal bioequivalence study to bridge the two formulations. In addition, Minerva believes the Phase 3 study has shown that US data and ex-US data are comparable, and that many precedents exist where drugs were approved by FDA based solely on ex-US data. Minerva believes that, in the Phase 3 study, results from the modified ITT (mITT) analysis set that excludes patients with implausible behavioral and physiological data from one site (17 of a total of 513 patients) addresses the lack of separation at Week 12.



2.

FDA's consideration of both ITT and mITT data analyses from Phase 3 study

In the briefing book for the Type C meeting, Minerva highlighted that the exclusion of implausible behavioral and physiological data from 17 patients at one site forms the basis of the mITT analysis set as outlined in the Statistical Analysis Plan submitted to FDA before unblinding the study.

For the mITT analysis set, the 64 mg dose of roluperidone achieved a nominal statistically significant result (p-value ? 0.044) on the primary endpoint, the Marder Negative Symptoms Factor Score (NSFS) of the Positive and Negative Syndrome Scale (PANSS). The details of both the ITT and mITT results for the primary (NSFS) and key secondary endpoint, the Personal and Social Performance (PSP) total score, can be found at the end of this press release.

FDA advised that their consideration of both the mITT and ITT results would be a matter of review and that in principle all sites should be included in the primary analysis set, and FDA cannot determine at this time whether data from the referenced site should be removed without a thorough evaluation. FDA indicated that Minerva should include justification for exclusion of these data in the future NDA package and provide primary results both with and without these data.

Other matters

In addition to the two main agenda items described above, the use of the PSP total score in the label and the adequacy of the PANSS and PSP instruments and related constructs to assess the efficacy of roluperidone were also discussed. Minerva expects to provide requested literature to support the instruments' psychometric properties to FDA.

Future development of roluperidone

Minerva intends to continue development and NDA activities consistent with FDA's December 2019 draft guidance titled "Demonstrating Substantial Evidence of Effectiveness for Human Drug and Biological Products." Where the target indication is an unmet need such as negative symptoms in schizophrenia, the guidance allows the FDA to consider one adequate and well-controlled study and confirmatory evidence as an alternative to two adequate and well-controlled studies to establish effectiveness.

"We thank FDA for their constructive approach and comments related to the development of roluperidone and their recognition of the significant unmet medical need which exists for patients and their families," said Dr. Remy Luthringer, Executive Chairman and Chief Executive Officer. "As a priority, we plan to communicate with FDA regarding their comments about the Phase 2b study, and continue to move forward with the clinical pharmacology, non-clinical, and CMC work needed to support an NDA submission. Following completion of the open label extension of the Phase 3 study, we expect to request a pre-NDA meeting with FDA to discuss the NDA submission plans based on the clinical efficacy and safety data. Minerva plans to share additional information as it becomes available."