BioXcel Therapeutics, Inc., a biopharmaceutical company utilizing artificial intelligence (AI) approaches to identify and develop transformative medicines in neuroscience and immuno-oncology, on Wednesday announced that the U.S. Food and Drug Administration (FDA) has approved IGALMI™ (dexmedetomidine) sublingual film for the acute treatment of agitation associated with schizophrenia or bipolar I or II disorder in adults.

IGALMI can be self-administrated by patients under the supervision of a healthcare provider. The Company is prepared to launch IGALMI in the U.S. in the second quarter of 2022.

Schizophrenia is a serious mental disorder in which people interpret reality abnormally. Schizophrenia may result in some combination of hallucinations, delusions, and extremely disordered thinking and behavior that impairs daily functioning, and can be disabling. People with schizophrenia require lifelong treatment.
Bipolar disorder, previously known as manic depression, is a mood disorder characterized by periods of depression and periods of abnormally-elevated happiness that last from days to weeks each. If the elevated mood is severe or associated with psychosis, it is called mania; if it is less severe, it is called hypomania.

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, said:

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. 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.

An estimated 7.3 million people in the U.S. are diagnosed with schizophrenia or bipolar disorders. Up to a quarter of these people experience agitation, with episodes that can occur 10 to 17 times annually, totaling up to 25 million agitation episodes for these two patient populations per year. Agitation episodes are associated with a significant burden for patients, caregivers, and the healthcare system.

Vimal Mehta, Ph.D., CEO of BioXcel Therapeutics, commented:

IGALMI is the first new acute treatment for schizophrenia or bipolar disorder-associated agitation in nearly a decade and represents a differentiated approach to helping patients manage this difficult and debilitating symptom. With this landmark achievement of our first approved drug, we have taken a monumental step toward our mission of bringing transformative medicines in neuroscience to patients using our AI platform. We are deeply grateful to our clinical trial participants, healthcare providers, researchers, and employees for contributing to this important new therapy. We believe IGALMI has significant market-changing potential, and we are excited to execute on our commercial launch plans in the U.S. this quarter.

The FDA approval of IGALMI 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, IGALMI met the primary endpoint at two hours after the first dose in patients treated with the 120 mcg and 180 mcg doses, demonstrating statistically significant improvements from baseline. IGALMI also met the key secondary endpoint, demonstrating a rapid onset of action, with statistically significant separation from placebo observed at 20 minutes for both the 180 mcg and 120 mcg doses in SERENITY II and 20 minutes and 30 minutes in SERENITY I, respectively.

The most common adverse reactions (incidence ≥5% and at least twice the rate of placebo) were somnolence (drowsiness and feeling sleepy), paresthesia or oral hypoesthesia, dizziness, dry mouth, hypotension (low blood pressure) and orthostatic hypotension. All adverse drug reactions were mild to moderate in severity. While IGALMI did not exhibit any treatment-related serious adverse effects (SAEs) in Phase 3 studies, it may cause notable side effects including hypotension, orthostatic hypotension and bradycardia, QT interval prolongation, and somnolence.

Data from the pivotal Phase 3 SERENITY II trial evaluating IGALMI in bipolar disorders were published in the Journal of the American Medical Association (JAMA) on February 22, 2022.8