The U.S. Food and Drug Administration (FDA) has approved dexmedetomidine (IGALMI, BioXcel Therapeutics), an orally dissolving sublingual film for mild, moderate or severe agitation in patients with schizophrenia or bipolar I or II disorder. Dexmedetomidine is a selective α-2A-adrenergic receptor agonist.
The orally dissolving film (ODF) is designed to rapidly dissolve and be absorbed sublingually or buccally, bypassing first-pass liver metabolism. The FDA approval is based on data from two pivotal randomized, double-blinded, placebo-controlled, parallel group Phase 3 trials evaluating IGALMI for the acute treatment of agitation associated with schizophrenia (SERENITY I) or bipolar I or II disorder (SERENITY II). In both trials, dexmedetomidine met the primary endpoint at two hours after the first dose in patients treated with the 120 µg,g and 180 µg,g doses, demonstrating statistically significant improvements from baseline.
The phase 3 SERENITY II trial included almost 380 adults with bipolar I or II disorder and acute agitation. The primary efficacy end point was the mean change from baseline at 2 hours for the Positive and Negative Syndrome Scale-Excited Component (PEC). Two hours after taking the medication, the mean changes from baseline in PEC total score were -10.4 for sublingual dexmedetomidine 180 µg, -9.0 for sublingual dexmedetomidine 120 µg, and -4.9 for placebo. Treatment effects began 20 minutes after taking the medication among patients in the sublingual dexmedetomidine groups. Mild to moderate adverse events (AEs) occurred in 35.7% of patients taking 180 µg of dexmedetomidine, 34.9% taking 120 µg, and 17.5% taking placebo. The most common AEs (=5%) were somnolence, dry mouth, hypotension, and dizziness. No drug-related severe or serious AEs occurred.
This sublingual dexmedetomidine formulation is a non-invasive treatment that avoids the need for injections and can be self-administered by the patient under the supervision of a healthcare provider. This novel mechanism of action and differentiating route of administration may make it potentially favored over current existing therapeutic options for treating agitation.
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Preskorn SH et al. JAMA. 2022;327(8):727. Abstract