Bifeprunox vs Placebo for Schizophrenia

Background

Bifeprunox is a novel antipsychotic drug designed to treat schizophrenia; however, research into the drug was ceased due to rejection of license to go to market by the US Food and Drug Administration (FDA) who could not approve the drug for acute or long-term symptoms of schizophrenia because more research was required to demonstrate convincing effects “beyond those already achieved” with currently licensed drugs. In addition, there were concerns expressed over one death of a person while on the drug.

Objectives

To review the effects of bifeprunox compared with placebo for schizophrenia.

Search Methods

We searched the Cochrane Schizophrenia Group’s Trials Register, October 23, 2015 and contacted authors of included studies.

Selection Criteria

All randomized clinical trials focusing on bifeprunox vs placebo for schizophrenia.

Data Collection and Analysis

We extracted data independently. For binary outcomes, we calculated risk ratio (RR) and its 95% CI, on an intention-to-treat basis. For continuous data, we estimated the mean difference (MD) between groups and its 95% CI. We employed a fixed-effect model for analyses.

Main Results

Four trials could be included. We found evidence of missing data and poor reporting. When bifeprunox was compared with placebo for schizophrenia, the mean change of the intervention groups for the Positive and Negative Syndrome Scale (PANSS) positive subscale was a 1.89 decline (n = 549, 2 randomized controlled trials [RCTs], MD CI 2.85–0.92, low quality) while the PANSS negative subscale showed a 1.53 decline (n = 549, 2 RCTs, MD CI 2.37–0.69, low quality). There was a clear difference regarding deterioration (n = 231, 1 RCT, RR 0.71, CI 0.54–0.93, very low quality) and measures of global state (figure 1). The total number of participants with ≥7% weight increase was similar between intervention and placebo (n = 483, 1 RCT, RR 1.00, CI 0.97–1.03, moderate quality). There was no usable data for the quality of life and economic outcomes.

Fig. 1.

Comparison: bifeprunox vs placebo. Outcome: global state: mean change (Clinical Global Impressions-Severity Scale [CGI-S], greater decline = good).

Authors’ Conclusions

The results from this review alone show some positive effects and favorable adverse effect profile for bifeprunox—although there are few data overall and none are of high quality. These data alone would not seem to have been enough for the FDA to make their decision to halt progress of the drug to market. We can only assume that we are missing important data. Both the FDA and the relevant pharmaceutical companies have not made all relevant data accessible. Because some of these trials also involved an additional haloperidol, olanzapine, quetiapine, or risperidone arm, these data are relevant to not only to evaluation of bifeprunox. In not making all data accessible it is hard to see how the FDA and the drug companies have fulfilled their full obligations to people with schizophrenia or their clinicians (for full details, please see Chattopadhyay et al¹).