Fabre-Kramer Pharmaceuticals, Inc.: Gepirone Hydrochloride Extended Release

We acknowledge receipt of your submissions dated May 1, 2007, July 13, 2007, & October 8, 2007.

The May 1, 2007 submission constituted a complete response to our June 23, 2004 action letter.

Therefore, the application is not approvable under section 505(d) of the Act and 21 CFR 314.125(b).

There are two major deficiencies in the application.

First you have failed to provide substantial evidence for the effectiveness of gepirone ER in the short-term or longer-term treatment of major depressive disorder (MDD).

Although this was not the protocol specified primary endpoint for 3 of the 12 trials, we felt it was a reasonable common measure because it is so widely used as a primary endpoint in depression trials.

In 2 of these 12 trials (CN105-053 and ORG 134006), an active comparator was superior to placebo and gepirone ER was not, as follows:

3.5%) and does not represent substantial evidence of effectiveness.

First, we disagree with your approach to trying to repair this study by establishing rules for identifying so-called protocol violators, either because they did not technically meet criteria for randomization or were non-compliant in some manner during the trial.

Thus, we do not find this post hoc attempt to rescue this study by eliminating 40 patients several years after the blind was broken credible or valid.

As noted in our June 23, 2004, not approvable letter for this application, it is difficult to know how to advise you regarding any future work with gepirone ER.

2. The provided stability data for the original biconvex tablets and the Organon modified flat tablets is not sufficient to support your request for 36 month expiration date for the drug product.

Within 10 days after the date of this letter, you are required to amend the application, notify us of your intent to file an amendment, or follow one of your other options under 21 CFR 314.120. If you do not follow one of these options, we will consider your lack of response a request to withdraw the application under 21 CFR 314.65. Any amendment should respond to all the deficiencies listed.

We will not process a partial reply as a major amendment nor will the review clock be reactivated until all deficiencies have been addressed.