Ahead of the FDA Action Date: A Timeline of Igalmi for Agitation in Bipolar Disorder and Schizophrenia

A dexmedetomidine sublingual film, approved as Igalmi in 2022 for acute agitation associated with schizophrenia or bipolar I or II disorder, is currently cleared only for use under the supervision of a health care provider. A supplemental New Drug Application (sNDA) seeks to extend that use to the at-home setting, with the US Food and Drug Administration (FDA)’s Prescription Drug User Fee Act action date set for November 14, 2026. The path to this decision spans a pre-sNDA meeting, a pivotal phase 3 safety trial, the sNDA submission, and a new efficacy analysis.

BXCL501 for Agitation Associated With Bipolar Disorders or Schizophrenia: Positive Pre-sNDA Meeting With FDA

BioXcel Therapeutics reported positive FDA responses ahead of a planned pre-sNDA meeting for BXCL501, the investigational formulation of dexmedetomidine sublingual film being studied for at-home treatment of agitation associated with bipolar disorders or schizophrenia. Written FDA comments received August 14, 2025, confirmed alignment on the content and format of the submission, including clinical, nonclinical, and chemistry, manufacturing, and controls requirements, so the company canceled the meeting originally scheduled for August 20, 2025. Acceptance of the sNDA remained subject to FDA review of the complete filing. Igalmi was approved only for use under health care provider supervision, in 120 mcg and 180 mcg strengths, and had not been studied beyond 24 hours. The package was to include data from the pivotal phase 3 SERENITY At-Home trial, a 12-week, double-blind, placebo-controlled safety study of the 120 mcg dose.

Primary End Point of Phase 3 Trial Met: BXCL501 for Agitation Associated With Bipolar Disorders or Schizophrenia

The pivotal phase 3 SERENITY At-Home trial of BXCL501 met its primary end point of tolerability in the at-home treatment of agitation associated with bipolar disorders or schizophrenia. The double-blind, placebo-controlled study enrolled approximately 246 participants, 45% with bipolar disorders and 55% with schizophrenia, and collected data on 2628 agitation episodes. Of 208 participants treated for 2437 episodes, 168 (81%) completed the 12-week trial, averaging 11.7 recorded episodes per treated participant, and all were able to self-administer BXCL501. No participants in the BXCL501 arm discontinued for tolerability, and the adverse event profile matched that of approved Igalmi, with no treatment-related serious adverse events, syncopes, or falls and no new or unexpected treatment-emergent events.

sNDA Submission: Igalmi for Acute Treatment of Agitation Associated With Bipolar Disorders or Schizophrenia in Outpatient Setting

BioXcel Therapeutics announced that it submitted an sNDA on January 14, 2026, seeking to expand the Igalmi label to allow acute treatment of agitation associated with bipolar disorders or schizophrenia at home, without health care provider supervision. Igalmi was approved in April 2022 for adults with agitation associated with schizophrenia or bipolar I or II disorder under supervision. That approval rested on 2 pivotal phase 3 trials, SERENITY I in schizophrenia and SERENITY II in bipolar disorder, in which the 120 mcg and 180 mcg doses met the primary end point at 2 hours after the first dose. Its safety and effectiveness had not been studied beyond 24 hours. The new submission was supported by results from the SERENITY At-Home safety trial.

New Analysis of BXCL501 At-Home Administration Shows Reduction of Agitation in Bipolar and Schizophrenia

An exploratory efficacy analysis from the SERENITY At-Home phase 3 trial, presented at the American Society of Clinical Psychopharmacology annual meeting, showed that BXCL501 reduced agitation compared with placebo across mild, moderate, and severe episodes, with the largest effect in severe episodes. Patients self-administered the film during agitation episodes for 12 weeks and completed a modified Clinical Global Impression-Severity scale before dosing and 2 hours afterward. The analysis covered 2628 episodes among 246 patients, and benefit persisted with repeated dosing regardless of baseline severity. More than 80% of patients completed the trial, no treatment-group discontinuations were due to tolerability, and there were no drug-related serious adverse events or signal of increasing adverse events over time. The FDA accepted the sNDA in April 2026 with a Prescription Drug User Fee Act action date of November 14, 2026.