SERENITY At-Home phase III trial evaluating BXCL 501, sublingual film formulation of dexmedetomidine, met its endpoint as an acute treatment for bipolar/schizophrenia agitation – BioXcel Therapeutics

-BioXcel Therapeutics, Inc announced that the SERENITY At-Home Pivotal Phase III trial evaluating the safety of BXCL 501, the Company’s proprietary, sublingual film formulation of dexmedetomidine, as an acute treatment for agitation associated with bipolar disorders or schizophrenia in the at-home setting, met its primary endpoint. The data from this successful study will form the basis of the sNDA submission for label expansion of Igalmi in the at-home setting planned for the first quarter of 2026.

“The SERENITY At-Home results are transformative in our journey toward outpatient use of BXCL 501 for the acute treatment of agitation associated with bipolar disorders or schizophrenia,” said Vimal Mehta, Ph.D., CEO of BioXcel Therapeutics. “By meeting its primary endpoint, the SERENITY At-Home Pivotal Phase III trial reinforces BXCL 501’s potential to be safely used at home like it is already used in the previously FDA approved institutional setting. The unmet medical need in the at-home setting is significant with no FDA approved treatments. We are committed to changing the treatment paradigm as we prepare for our planned sNDA submission intended to provide patients with access to Igalmi in the home setting. We believe the total addressable market is significantly larger than previously reported.”

“The management of agitation associated with bipolar disorder and schizophrenia in the home setting is an important clinical challenge where we currently have few optimal options,” said Dr. John Krystal, M.D., the Robert L. McNeil, Jr. Professor of Translational Research and Chair of the Department of Psychiatry at Yale School of Medicine. “Timely intervention has the potential to mitigate patient distress, decrease emergency room visits, and enhance overall patient safety while reducing healthcare costs, and I am pleased that this promising data could pave the way for a potential first approval of BXCL501 for at-home treatment.”

The SERENITY At-Home Pivotal Phase III trial is a double-blind, placebo-controlled 12 week trial designed to evaluate the safety of a 120 mcg dose of BXCL 501 for the acute treatment of agitation associated with bipolar disorders or schizophrenia in the at-home setting.

SERENITY At-Home Topline Summary

• Summary of agitation episodes:
  • A total of 246 patients randomized
  • Data collected 2628 agitation episodes in 215 patients
  • Treated 2437 episodes in 208 patients
    • 168 patients (81%) completed the full 12-week trial
  • Average of 11.7 agitation episodes recorded per treated patient
• All patients were able to successfully self-administer the film
• Distribution of enrolled patients was 45% bipolar disorders and 55% schizophrenia

SERENITY AT-Home Primary Endpoint Data

Ti.he 120 mcg dose of BXCL 501 was well-tolerated in patients with episodes of agitation in the outpatient setting and met the primary objective. This tolerability outcome was observed across repeat dosing and through the duration of the trial.

• ii.No discontinuations due to tolerability in the BXCL 501 arm
• iiii Adverse event profile consistent with approved Igalmi label and multiple clinical trials in the institutional setting
  • iv.No drug-related serious adverse events (SAEs), syncopes or falls reported
  • v.No new or unexpected treatment emergent adverse events (TEAEs)
  • vi.No severe TEAEs associated with BXCL501 treatment and most TEAEs were mild
  • vii.No trend of more frequent AEs over time or with repeat dosing
• viii. Tolerability remained consistent throughout the repeat dosing in the trial.
• ERENITY At-Home Preliminary Exploratory Data
• The efficacy of Igalmi has already been established in the institutional setting in the SERENITY I and II trials that led to FDA approval . The available topline data for the exploratory endpoints from more than 2400 episodes in SERENITY At-Home demonstrates that treatment with BXCL 501 regularly reduced symptoms of agitation throughout the trial. A greater percentage of patients experiencing mild, moderate, or severe agitation had full resolution of symptoms in the BXCL 501 arm compared with placebo. The initial results demonstrate continued effects and consistent benefit with repeat dosing across the course of the trial.
• Complete analyses of the full data set is ongoing, and results will be shared in the near future.
• “We are pleased with the positive results and consistent tolerability profile demonstrated for BXCL 501 in more than 1100 self-administered treated episodes in the at-home setting,” Matt Mandel, M.D., Vice President of Clinical Development at BioXcel Therapeutics, stated. “With efficacy already established for the 120mcg dose of Igalmi, demonstrating evidence of benefit to patients with repeat dosing in the outpatient setting is highly encouraging. We believe the totality of the evidence, combined with the favorable tolerability, supports our planned regulatory submission and positions BXCL501 to potentially become the first at-home treatment for this critical unmet need affecting patients and their families.”
• BXCL 501 is currently FDA-approved and marketed for the acute treatment of agitation associated with bipolar I or II disorder or schizophrenia in medically supervised settings. Igalmi is available in 2 dose strengths, 120 mcg and 180 mcg. To support the potential label expansion for at-home use, an important part of the regulatory package will be data from this SERENITY At-Home Pivotal Phase III trial, which is a double-blind, placebo-controlled 12-week study designed to evaluate the safety of a 120 mcg dose of BXCL 501 for the acute treatment of agitation associated with bipolar disorders or schizophrenia in the at-home setting. The trial design and protocol were previously agreed to with FDA.
• There are no FDA-approved therapies for the acute treatment of agitation in the at-home setting.