- Acadia Pharmaceuticals won't continue studying its neurological disease drug pimavanserin in schizophrenia patients who don't respond well to antipsychotic therapy, announcing Monday afternoon negative results from a Phase 3 study in that treatment setting.
- Data showed adding pimavanserin to drugs like Risperdal or Abilify didn't reduce schizophrenia symptoms by any more than antipsychotic treatment alone when measured using a disease scale known as PANSS. Acadia did note, however, a slight improvement on a secondary endpoint looking only at the so-called "negative" symptoms of the mental illness.
- Pimavanserin, approved in the U.S. for treatment of hallucinations associated with Parkinson's disease psychosis, is Acadia's main drug, and carving out new indications for its use is the biotech's principal development strategy. Shares in the company fell in Tuesday trading in response to the news.
Acadia executives admitted pimavanserin's trial failure but, with a Phase 2 study of the drug in schizophrenia still ongoing, spent time on a Monday conference call trying to persuade investors of a silver lining.
That mid-stage trial is also testing pimavanserin as an add-on treatment to antipsychotics, but focuses on patients with predominantly negative symptoms rather than on those with an inadequate response to background therapy. Negative symptoms like withdrawal manifest as an absence, rather than "positive" symptoms such as hallucinations.
Acadia's Phase 3 study found pimavanserin ineffective on reducing both positive and negative symptoms, but showed a statistical sliver of improvement when only negative symptoms were measured.
"In the six-week trial, the effect that we saw are, to us, encouraging," said Serge Stankovic, Acadia's president, on the conference call.
Results from the Phase 2 study, which is designed to run for six months, are due later this year and could be used in an application to the Food and Drug Administration if positive, noted Acadia CEO Steve Davis.
Still, the Phase 3 data on negative symptoms only barely cleared the threshold to show a statistical difference versus the control arm — making Acadia's optimistic outlook a tougher sell.
Acadia executives also noted geographical differences in how patients responded to pimavanserin. The Phase 3 study was mostly run out of sites in Central and Eastern Europe, with less than 20% of the 396 patients in the trial enrolled at sites in the U.S. and Canada.
"The unique challenge for schizophrenia studies in particular is the variability of results that can be seen among clinical trial sites in the United States, relative to other regions," said Davis, citing the frequency at which U.S. patients are treated at sites where they have never received care before.
Looking only at a subgroup of European patients, Acadia found a significant result on the primary PANSS measure of both positive and negative symptoms.
Relying on subgroup analyses to prove a benefit can be a fraught endeavor, however, thanks to a lack of statistical robustness in the positive signs highlighted by executives, however. Acadia investors seemed to agree, sending shares in the company down by nearly 15% Tuesday.
Acadia is also studying pimavanserin in dementia-related psychosis and major depressive disorder.