Acadia falls on negative trial result in schizophrenia – US biotech Acadia Pharmaceuticals (Nasdaq: ACAD) saw its stock fall by 15% today on the back of a negative top-line result from its 396-patient “Enhance” Phase III study of Nuplazid (pimavanserin) in treatment resistant schizophrenia. The company, which is a mid-size holding of the UK’s International Biotechnology Trust (IBT), has an approval in the US for Nuplazid in Parkinson’s Disease psychosis and has working to expand the label into other areas.
The company reported yesterday that the Enhance study failed to meet its goal of showing a statistically significant difference (ie p<0.05) on the Positive and Negative Syndrome Scale (PANSS) total score (p=0.0940). The company claimed the results did show a consistent trend (usually code for p<0.1) in psychotic symptoms and in a key secondary endpoint, the Clinical Global Impression-Severity (CGI-S) score (p=0.0543). It also noted the majority of patients in the study were enrolled in Europe (>80%) and consistent positive results were observed on PANSS total score (unadjusted p=0.0234), and CGI-S score (unadjusted p=0.0214) in this pre-specified subgroup (this however, suggests there is must have been worse results in non-European patients). (Note, sub-group results would normally be expected to reach a higher level of statistical confidence (say, p<0.025) in order to be declared significant, so as to compensate for the effect of multiple analyses, and in any case this is only possible after a positive result in the primary analysis).
The company also stated that in the full analysis set, Nuplazid showed significant improvements on two pre-specified measures of negative symptoms: PANSS negative symptoms scale sub-score (unadjusted p=0.0474) and PANSS Marder negative factor score (unadjusted p=0.0362). Negative symptoms of scizophrenia are those such as apathy, lack of emotion and poor social functioning and are considered more difficult to treat than positive sumptoms such as hallucinations and delusions.
The company is conducting a Phase II study called Advance in negative symptoms of schizophrenia, which should read out soon, and if positive this may become the focus of future clinical development in the condition. Acadia is also conducting the “Harmony” Phase III study in dementia related psychosis, for which an interim readout is expected later this year with a possible early efficacy stop before its scheduled completion next year.
Acadia has recently initated the Clarity-2 Phase III study (and plans to initiate a similar “Clarity-3 study shortly) to evaluate Nuplazid in major depressive disorder with inadequate response to standard antidepressant therapy.