FDA Approves Gepirone Extended-Release for Treatment of Major Depressive Disorder

Ashley Gallagher, Associate Editor

Gepirone hydrochloride ER (Exxua; Fabre-Kramer Pharmaceuticals Inc) is in a new class of antidepressants, making it the first and only approved antidepressant that selectively targets serotonin 1A receptors.

The FDA has announced the approval of gepirone hydrochloride extended-release (ER) tablets (Exxua; Fabre-Kramer Pharmaceuticals Inc) for the treatment of adults with major depressive disorder (MDD).1

Argus – stock.adobe.com

Gepirone ER is reported to be in a new class of antidepressants, making it the first and only approved antidepressant that selectively targets serotonin 1A receptors, which are key in regulating mood and emotions. The drug is expected to be available in early 2024.1

“I am thrilled for our patients that gepirone ER is now FDA approved for the treatment MDD. Gepirone ER is the first 5-HT1a agonist with superior efficacy vs placebo as MDD monotherapy yet did not differ from placebo in rates of sexual dysfunction in clinical trials. This provides an important new treatment option for patients,” Anita H Clayton MD, chair of the department of psychiatric and neurobehavioral sciences at the University of Virginia School of Medicine, said in a statement.1

According to the statement, the mechanisms of the antidepressant effect is not entirely understood; however, investigators believe that it is related to modulation of serotonin activity in the central nervous system and through selective agnostic activity for 5-HT1a receptors. The study investigators said the active metabolites are exclusive and have a strong binding affinity for 5-HT1a receptors.1

Investigators studied the drug in more than 5000 patients, in whom the drug had an acceptable adverse effect (AE) profile, according to the statement. The investigators reported that the sexual effects with gepirone ER in the clinical trials was comparable to the placebo and did not meet the criteria for inclusion on the AE section of the drug’s label.1

Furthermore, they reported that the overall safety profile was acceptable, stating that there were no AEs on weight, blood pressure, heart rate, or liver function. The most frequent AEs in the clinical studies included dizziness and nausea, which were reported to be mild, short in duration, related to dose escalation, and did not lead to discontinuation of treatment.1

“The mental health crisis in the United States is one of the most pressing health issues facing our country today . . . The need for new treatment options, particularly those with new mechanisms of action, could not be clearer and more urgent for those living with, or impacted by [MDD],” Michael Pollack, CEO of the Depression and Bipolar Support Alliance, said in the statement.1

According to the National Library of Medicine, MDD was ranked the third cause of disease burden globally in 2008 by the World Health Organization, with a projection that the disease will be ranked first by 2030.2

Traditionally, MDD is treated by FDA-approved medications such as selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, serotonin modulators, atypical antidepressants, tricyclic antidepressants, and monoamine oxidase inhibitors. Other treatments included mood-stabilizers and antipsychotics.2 The authors reported that combination treatment of both medications and psychotherapy are more effective than either of the treatments alone.2

This new class of antidepressants has the potential to significantly improve MDD treatment, according to the study investigators.1

Reference

Fabre-Kramer Pharmaceuticals announces FDA approval of Exxua, the first and only oral selective 5HT1a receptor agonist for the treatment of major depressive disorder in adults. News release. PR Newswire. September 28, 2023. Accessed September 28, 2023. https://www.prnewswire.com/news-releases/fabre-kramer-pharmaceuticals-announces-fda-approval-of-exxua-the-first-and-only-oral-selective-5ht1a-receptor-agonist-for-the-treatment-of-major-depressive-disorder-in-adults-301941467.html#:~:text=Exxua%20has%20been%20shown%20to,in%20pharmacies%20in%20early%202024

Bains N, Abdijadid S. Major Depressive Disorder. In: StatPearls. Treasure Island (FL): StatPearls Publishing; April 10, 2023. Accessed September 28, 2023. https://www.ncbi.nlm.nih.gov/books/NBK559078/FDA Approves Gepirone Extended-Release for Treatment of Major Depressive DisorderSeptember 28, 2023Ashley Gallagher, Associate EditorNewsArticleGepirone hydrochloride ER (Exxua; Fabre-Kramer Pharmaceuticals Inc) is in a new class of antidepressants, making it the first and only approved antidepressant that selectively targets serotonin 1A receptors.The FDA has announced the approval of gepirone hydrochloride extended-release (ER) tablets (Exxua; Fabre-Kramer Pharmaceuticals Inc) for the treatment of adults with major depressive disorder (MDD).1Argus – stock.adobe.com

Gepirone ER is reported to be in a new class of antidepressants, making it the first and only approved antidepressant that selectively targets serotonin 1A receptors, which are key in regulating mood and emotions. The drug is expected to be available in early 2024.1″I am thrilled for our patients that gepirone ER is now FDA approved for the treatment MDD. Gepirone ER is the first 5-HT1a agonist with superior efficacy vs placebo as MDD monotherapy yet did not differ from placebo in rates of sexual dysfunction in clinical trials. This provides an important new treatment option for patients,” Anita H Clayton MD, chair of the department of psychiatric and neurobehavioral sciences at the University of Virginia School of Medicine, said in a statement.1According to the statement, the mechanisms of the antidepressant effect is not entirely understood; however, investigators believe that it is related to modulation of serotonin activity in the central nervous system and through selective agnostic activity for 5-HT1a receptors. The study investigators said the active metabolites are exclusive and have a strong binding affinity for 5-HT1a receptors.1Investigators studied the drug in more than 5000 patients, in whom the drug had an acceptable adverse effect (AE) profile, according to the statement. The investigators reported that the sexual effects with gepirone ER in the clinical trials was comparable to the placebo and did not meet the criteria for inclusion on the AE section of the drug’s label.1Furthermore, they reported that the overall safety profile was acceptable, stating that there were no AEs on weight, blood pressure, heart rate, or liver function. The most frequent AEs in the clinical studies included dizziness and nausea, which were reported to be mild, short in duration, related to dose escalation, and did not lead to discontinuation of treatment.1″The mental health crisis in the United States is one of the most pressing health issues facing our country today . . . The need for new treatment options, particularly those with new mechanisms of action, could not be clearer and more urgent for those living with, or impacted by [MDD],” Michael Pollack, CEO of the Depression and Bipolar Support Alliance, said in the statement.1According to the National Library of Medicine, MDD was ranked the third cause of disease burden globally in 2008 by the World Health Organization, with a projection that the disease will be ranked first by 2030.2Traditionally, MDD is treated by FDA-approved medications such as selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, serotonin modulators, atypical antidepressants, tricyclic antidepressants, and monoamine oxidase inhibitors. Other treatments included mood-stabilizers and antipsychotics.2 The authors reported that combination treatment of both medications and psychotherapy are more effective than either of the treatments alone.2This new class of antidepressants has the potential to significantly improve MDD treatment, according to the study investigators.1Reference

Fabre-Kramer Pharmaceuticals announces FDA approval of Exxua, the first and only oral selective 5HT1a receptor agonist for the treatment of major depressive disorder in adults. News release. PR Newswire. September 28, 2023. Accessed September 28, 2023. https://www.prnewswire.com/news-releases/fabre-kramer-pharmaceuticals-announces-fda-approval-of-exxua-the-first-and-only-oral-selective-5ht1a-receptor-agonist-for-the-treatment-of-major-depressive-disorder-in-adults-301941467.html#:~:text=Exxua%20has%20been%20shown%20to,in%20pharmacies%20in%20early%202024

Bains N, Abdijadid S. Major Depressive Disorder. In: StatPearls. Treasure Island (FL): StatPearls Publishing; April 10, 2023. Accessed September 28, 2023. https://www.ncbi.nlm.nih.gov/books/NBK559078/