Decadeslong regulatory odyssey ends with FDA nod for Fabre-Kramer's depression med Exxua

Fabre-Kramer Pharmaceuticals' major depressive disorder (MDD) drug gepirone has been rejected by the FDA not once, not twice, but three times since the turn of the millennium.

Now, the company can finally celebrate a victory with a long-awaited approval.

Gepirone, branded as Exxua, will enter the antidepressant market next year and inaugurate an entirely new class of medicines. It’s the first approved drug in the disorder that selectively targets the serotonin 1A receptor, which is key in regulating mood and emotion, according to a press release from the Houston-based company.

Aside from its unique mechanism of action, Exxua sets itself apart in the depression market with a label that's free of warnings or side-effect language detailing risks of weight gain or sexual dysfunction.

Exxua is expected to be available in pharmacies by early 2024, Fabre-Kramer said.

“We are proud to bring this innovative therapy to patients who need a new option to manage their depression and improve their quality of life,” Fabre-Kramer CEO Stephen Kramer, M.D., said in a statement.

The drug has changed hands several times since its 1986 invention by Bristol Myers Squibb, which then licensed it to Fabre-Kramer. Organon was next to get its hands on it, only to return the prospect to Fabre-Kramer after the FDA nixed approval applications in 2002 and 2004.

For Exxua’s third go-around, Fabre-Kramer linked up with GSK in a licensing deal. That attempt didn’t work out either, and the companies in 2007 received a not approvable letter from the agency, which would now be known as a complete response letter. GSK later exited the partnership.  

Previously, the FDA voiced concerns over a clutch of failed studies that outweighed the few positive ones. In 2012, the company appealed the most recent rejection, culminating in a 2015 advisory committee hearing.     

The following year, the FDA’s Office of New Drugs decided that the med does in fact demonstrate evidence of effectiveness in MDD, overturning its previous position and opening the door to an approval.

Fabre-Kramer is also studying Exxua in generalized anxiety disorder and hypoactive sexual desire disorder.