Is the Fourth Time the Charm for This Antidepressant?

A pharmaceutical company behind an antidepressant that began development more than three decades ago and has been rejected by the FDA three times in the past is hoping that the fourth time before the agency will by the charm.

The FDA’s Psychopharmacologic Drugs Advisory Committee is meeting today in Silver Spring, Md., to again decide the fate of Fabre-Kramer Pharmaceuticals’ gepirone hydrochloride extended-release. The agency previously rejected an NDA for the drug in 2002, 2004 and 2007.

The first two rejections were because the FDA could find only one positive trial for gepirone. Usually, two or more positive studies are needed to garner approval. Fabre-Kramer achieved that in 2007, but gepirone was nonetheless rejected a third time over concerns raised in failed trials. In 2007, Fabre-Kramer was partnered with GlaxoSmithKline on the drug, but the British drugmaker has since dropped from the collaboration.

Gepirone was originally developed by Bristol-Myers Squibb, but licensed to Fabre-Kramer in 2007. It is classified as both an antidepressant and antianxiolytic of the azapirone class, and acts as a selective partial agonist of the 5-HT1A receptor, which binds the neurotransmitter serotonin.

Three years ago, Fabre-Kramer appealed the 2007 decision to the director of the FDA’s Office of New Drugs, which granted yet another advisory committee review of gepirone.

In documents Fabre-Kramer presented to the committee, the company argued that some of the geprione studies should be considered “uninterpretable” and thus excluded from the committee’s consideration. Also, they claim an analysis of other studies demonstrates the benefits of the drug.

In its own memo, the FDA begged to differ, writing that the plethora of  negative or failed trails seems to indicate that the two positive trails may have occurred by chance.

Even if Fabre-Kramer is successful, the commercial success of gepirone is unclear, as the market for antidepressants and anti-anxiety drugs is shrinking, according to a new report from Transparency Market Research.