FDA Approves Gepirone Hydrochloride Tablets for Major Depression

A new class of antidepressants have reached the US market.

The US Food and Drug Administration (FDA) has approved gepirone hydrochloride extended-release tablets (Exxua) for the treatment of major depressive disorder (MDD) in adult patients. The indication, granted to Fabre-Kramer Pharmaceuticals, denotes the product as the first antidepressant that selectively targets the serotonin 1A receptor—a regulator of mood and emotion.¹

The mechanism of action behind gepirone hydrochloride, a single serotonin (5HT) 1a receptor agonism, is still not fully understood by investigators, but is theorized to relate to the modulation of central nervous system serotonin activity through the selective receptor targeting.

"EXXUA is the first truly selective agonist of the serotonin 1a receptor that has been consistently linked to mediation of mood disorders and suicide risk,” neuropsychopharmacologist Stephen Stahl, MD, PhD, professor of psychiatry at the University of California and founder of the Neuroscience Education Institute, said. “It's an important addition to the armamentarium to treat depression.”

Gepirone hydrochloride’s clinical efficacy was supported by data from a pair of 8-week, double-blind, placebo-controlled trials including adult patients aged 18 – 69 years old with MDD. Patients were randomized 1:1 to either initial 18.2 mg dose treatment—titrated to 72.6 mg daily doses—or placebo. Investigators sought a primary endpoint of change from baseline in Hamilton Depression Rating Scale (HAMD-17) total score at week 8.²

The team reported that gepirone hydrochloride was associated with significantly greater improvement per HAMD-17 total score versus placebo at week 8, in both the first (-2.47 [95% CI, -4.41 to -0.53; P = .013]) and second (-2.45 [95% CI, -4.47 to -0.43; P = .018) trial.

Patients commonly experienced adverse events including dizziness, nausea, insomnia, abdominal pain, and dyspepsia. Marketed EXXUA will including a Boxed Warning in its prescribing information for risk of suicidal thoughts and behavior. Dosage strengths range from 18.2 mg; 36.3 mg; 54.5 mg; and 72.6 mg.

In a statement accompanying the approval, Anita H. Clayton, MD, chair of the department of psychiatry & neurobehavioral sciences at the University of Virginia School of Medicine, described gepirone hydrochloride as an “important new treatment option” for patients with MDD.

“I am thrilled for our patients that gepirone ER is now FDA approved for the treatment of MDD,” Clayton said. “EXXUA is the first 5-HT1a agonist with superior efficacy versus placebo as MDD monotherapy, yet did not differ from placebo in rates of sexual dysfunction in clinical trials.”

References

1. ^{Cision PR Newswire. 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. Press release. Published 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}
2. ^{Park B. Exxua, a Novel Treatment for Major Depressive Disorder, Gets FDA Approval. Medical Professionals References. Published September 28, 2023. https://www.empr.com/home/news/exxua-a-novel-treatment-for-major-depressive-disorder-gets-fda-approval/?utm_source=eloqua&utm_medium=email&utm_campaign=NWLTR_MPR_DAYD_092823_AL&hmemail=&sha256email=cb0550bc618e627adde145de0d4ed89fab9c9558d24beb280db55f44d7cc891f&hmsubid=&nid=}