Minerva Neurosciences Announces Outcome of Type C Meeting with FDA and Next Steps in the Development of Roluperidone - Seite 2
2. FDA’s consideration of both ITT and mITT data analyses from Phase 3
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.
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Minerva intends to continue development and NDA activities consistent with FDA’s December 2019 draft guidance titled “Demonstrating Substantial Evidence of Effectiveness for Human Drug and Biological Products.”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.”