Exxua (gepirone)

by Rebecca Lee, P4

On September 22nd of this year, the FDA approved the first and only selective 5-HT1A serotonin receptor agonist for the treatment of Major Depressive Disorder (MDD) in adults after more than two decades of regulatory obstacles.1

Since 2002, Exxua (gepirone) had been rejected by the FDA three times before finally obtaining approval this year. The efficacy of this drug was evaluated in two eight-week randomized, doubleblind, placebo-controlled, flexible-dose studies in adults aged 18 to 69 years diagnosed with MDD.2 The primary outcome measured the change from baseline in the Hamilton Depression Rating Scale (HAMD-17) total score after eight weeks. In both studies, patients in the medication treatment groups experienced statistically significantly greater improvement on the primary endpoint compared to patients in the placebo groups, as shown in the table below.

Study Treatment Group Mean Baseline Score (SD)

Some adverse events observed include dizziness, nausea, insomnia, abdominal pain, and dyspepsia. Unlike many other serotonergic antidepressants, Exxua does not come with a warning for sexual dysfunction or weight gain. Additionally, it has no significant adverse effects on blood pressure, heart rate, and liver function.2,3 Exxua is available as an extended-release oral tablet at strengths of 18.2 mg, 36.3 mg, 54.5 mg, and 72.6 mg.2

Similar to the treatment of many other psychiatric conditions, Major Depressive Disorder (MDD) involves a vague and individualized approach to therapy. Instead of recommending specific agents, guidelines typically suggest classes of medications, with no evidence of higher efficacy of any single agent over another. Consequently, practitioners must assess the nuances of each agent and individualize therapy for each patient, potentially requiring multiple medication

Least-Squares Mean CFB (SE)

Placebo-subtracted Difference (95% CI)

1 EXXUA(N=101) 22.7 (2.45) -9.04 (0.78) -2.47 (-4.41, -0.53)

Placebo (N=103) 22.8 (2.51) -6.75 (0.77)

2 EXXUA(N=116) 23.9 (2.69) -10.22 (0.75) -2.45 (-4.47, -0.43)

Placebo (N=122) 24.2 (2.92) -8.96 (0.73)

SD = Standard Deviation, CFB = Change from baseline, SE = Standard Error, CI = Confidence Interval

In study 1, the final dose of EXXUAwas 72.6 mg/day in 64%, 54.5 mg/day in 20%, and 36.3 mg/day in 17% of patients

In study 2, the final dose of EXXUAwas 72.6 mg/day in 66%, 54.5 mg/day in 22%, 36.3 mg/day in 10%, and 8.2 mg/day in 2% of patients

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VersionId=IC2bomk7brcgK.ONoXIYN9fk56IwuwU7 trials to achieve therapeutic success. Therefore, having agents with varying unique mechanisms of action is ideal for finding treatment success for each patient. The approval of Exxua as the first and only agent specifically targeting the 5-HT1A receptor represents a significant advancement in the field of psychiatric medicine. Its mechanism and clinical outcomes also show potential for other therapeutic areas and indications, including anxiety and sexual dysfunction.

References

1. Becker Z. Decadeslong Regulatory Odyssey ends with FDA nod for Fabre-Kramer’s depression Med Exxua. Fierce Pharma. September 28, 2023. Accessed November 2, 2023. https://www.fiercepharma.com/pharma/fourth-times-charm-fabre-kramers-novel-depression-med-exxua-finally-cross-fda-finish-line.

2. Exxua (gepirone). Package insert. Fabre-Kramer Pharmaceuticals, Inc.; 2023.

3. Heidi D. FDA Approves First Oral Selective 5HT1A Receptor Agonist for MDD. Psychiatric Times. September 28, 2023. Accessed November 2, 2023. FDA Approves First Oral Selective 5HT1A Receptor Agonist for MDD