Tuesday, August 25, 2009

Iloperidone Approved as “Second-Generation” Benefits Debated

The FDA recently approved iloperidone (Fanapt, Vanda Pharmaceuticals) for the treatment of schizophrenia, reversing a July 2008 determination that the New Drug Application (NDA) was “not approvable.” An FDA spokesperson explained in an interview in Forbes (May 8), “Vanda provided the FDA with additional data and arguments that led us to reinterpret results of several of their studies.”

The favorable judgment culminated a circuitous product development path. The compound had been developed by Hoechst Marion Roussel, but the rights were sold to Titan Pharmaceuticals in 1997, and then to Novartis in 1998, before Vanda Pharmaceuticals acquired them in 2004. Vanda succeeded in garnering regulatory approval, in large part by redesigning the clinical trials supporting the NDA.

Rather than comparing the efficacy of iloperidone with risperidone and haloperidol, which had not previously favored iloperidone, the new trials compared iloperidone with placebo and used ziprasidone as an active control. In this design, the active agents were shown to have comparable efficacy in improving symptoms measured on the 30-item Positive and Negative Syndrome Scale (PANSS) and were both statistically superior to placebo.