Kyowa Pharmaceutical, Inc.: istradefylline

Please refer to your new drug application(NDA) dated March 29, 2007, received April 25, 2007, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act for oe (istradefylline) tablets | 20mg, and 40mg.

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

We acknowledge that you have submitted three well-controlled studies (Studies 005, 006, and 013) that show effectiveness for the adjunctive use of istradefylline 20mg, 40mg, and 60mg/day (without clear evidence of dose response) in decreasing the percent of time awake spent in the OFF state in patients with advanced Parkinson's Disease (PD).

Several other well-controlled studies of adequate size, however, do not show such an effect and in one of those studies, Study EU-007, an active control, entacapone, gave an almost significant result (p=0.06) while istradefylline showed essentially no effect.

PD show advantages compared to placebo on signs and sympto does not is based on cross-study comparisons, which are typical that the totality of the evidence justifies our concerns.

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.