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The FDA approved the first and only orally dissolving film for schizophrenia and bipolar-related agitation, .

Acting as an alpha2-adrenergic receptor agonist, dexmedetomidine (Igalmi) is indicated for mild, moderate, or severe agitation in patients with schizophrenia or bipolar I or II disorder.

Fast acting, the sublingual film is able to quell agitation in as quickly as 20 minutes. The new dexmedetomidine formulation comes in 120 mcg and 180 mcg doses, but may also be cut in half to achieve 60 mcg and 90 mcg doses. It can be either self-administered or under the supervision of a healthcare provider (other currently available versions of dexmedetomidine require intramuscular injection).

"There are large numbers of patients who experience agitation associated with schizophrenia and bipolar disorders, and this condition has been a long-standing challenge for healthcare professionals to treat," said John Krystal, MD, of Yale School of Medicine in New Haven, Connecticut, in a statement. "The approval of Igalmi, a self-administered film with a desirable onset of action, represents a milestone moment. It provides healthcare teams with an innovative tool to help control agitation. As clinicians, we welcome this much-needed new oral treatment option."

Underpinning this approval was a pair of phase III trials: SERENITY I focused on patients with schizophrenia, and SERENITY II on patients with bipolar I and II disorder. The findings were first presented at the 2021 American Psychiatric Association virtual meeting and recently published in .

In the trial of 380 patients with schizophrenia, the 120 mcg dose yielded an average 8.5-point reduction in Positive and Negative Syndrome Scale (PANSS)-Excited Component (PEC) total score from baseline within 2 hours versus a 4.8-point improvement with placebo. Those treated with a 180 mcg dose saw a 10.3-point drop in total score within 2 hours of dosing.

After 2 hours, 79.1% and 88.8% of those on the 120 mcg and 180 mcg doses, respectively, were considered responders to treatment versus only 40% of those on placebo.

In the trial, a repeat half dose could be given 2 hours following the initial dose if the PEC score change from baseline was less than 40% and there were no safety concerns. However, the maximum number of repeat doses was capped at two within 12 hours of the initial dose.

Similar results were seen in the 380-person study of patients with bipolar disorder. Those on 120 mcg and 180 mcg doses saw an average drop in PEC total score from baseline of 9.1 and 10.4, respectively, after 2 hours versus a drop of only 5.0 with placebo.

The most common adverse reactions seen with the film were somnolence, paresthesia or oral hypoesthesia, dizziness, dry mouth, hypotension, and orthostatic hypotension.

The outlines an initial dose recommendation for specific patent populations, with a starting dose of 120 mcg for adults with mild or moderate agitation and 180 mcg for severe agitation. Those with hepatic impairment are advised to start on lower initial doses (as low as 60 mcg), and patients ages 65 and older should receive an initial dose of 120 mcg, regardless of agitation severity.

Dexmedetomidine should be avoided in patients with risk factors for prolonged QT interval. It should also be avoided in patients with hypotension, orthostatic hypotension, advanced heart block, severe ventricular dysfunction, or history of syncope.

BioXcel announced plans for a U.S. commercial launch in the next few months.

The developer also recently announced findings of the phase III TRANQUILITY trial, testing the agent in with agitation, for which the FDA granted breakthrough therapy designation last year.

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