Acadia Pharma’s plan to develop pimavanserin as a treatment for additional indications is in disarray after the drug failed a phase 3 trial in schizophrenia.
The company said it doesn’t intend to carry out any more trials of pimavanserin, disappointing investors and driving its shares down nearly 19% in after-hours trading.
The drug is already approved as Nuplazid for psychosis caused by Parkinson’s disease, but Acadia’s efforts to extend its label have been fruitless, with the latest failure following FDA rejections of the drug for dementia and Alzheimer’s disease-related psychosis in 2021 and 2022.
In the ADVANCE-2 trial, pimavanserin was unable to show a statistically significant improvement over placebo on the study’s primary endpoint, the change from baseline to week 26 on the Negative Symptom Assessment-16 (NSA-16) total score. Acadia said the trial was affected by a higher-than-expected improvement in symptoms in the placebo arm.
While current antipsychotics are effective at treating positive symptoms of schizophrenia like hallucinations and delusions, they tend to be ineffective at negative symptoms like a lack of motivation, social withdrawal and blunted emotions.
Pimavanserin’s failure in the trial is another heavy blow to patients and clinicians hoping for the first approved therapy for this hard-to-treat aspect of schizophrenia, coming after the FDA rejected Minerva Neurosciences’ marketing application for its drug candidate roluperidone.
Acadia’s chief executive Steve Davis said the company was “disappointed” by the data and, while it will continue to analyse the results, confirmed that the company will not conduct any additional trials of pimavanserin.
Nuplazid is doing well in its approved indication, bringing in around $550 million in sales last year, but it accounts for almost three-quarters of Acadia’s total revenues and the company will now have to look elsewhere for its future growth.
The company will be hoping for positive news with its other pipeline drugs, which include ACP-101 (intranasal carbetocin) for the treatment of hyperphagia in Prader-Willi syndrome (PWS), in the phase 3 COMPASS PWS trial, and 5-HT2A receptor inverse agonist ACP-204 for Alzheimer’s psychosis in phase 2.
It also has a candidate called ACP-2591 with potential in Rett syndrome and Fragile X syndrome which is in early clinical development.
ICER delivers its verdict on KarXT
One new treatment for schizophrenia that could be on the horizon is Karuna Therapeutics’ M1/M4 muscarinic receptor agonist KarXT (xanomeline tartrate/trospium chloride), which was filed for approval in the US last November and could be the first drug with an entirely new mechanism of action to reach the market in decades.
The influential Institute for Clinical and Economic Review (ICER) in the US has released the final version of a report on KarXT, suggesting that the current evidence is “not adequate to demonstrate superior net health benefits for KarXT compared to generically available aripiprazole,” although it did seem to be better than two other generics, olanzapine and risperidone.
Given that conclusion, ICER has set a pretty low cost-effectiveness threshold for the drug, suggesting it should be priced at between $16,000 and $20,000 per year. A recent study estimated the total cost of schizophrenia in the US to be around $16,000 per patient per year, with approximately $5,000 of that total accounted for by medications.
Bristol-Myers Squibb announced a $14 billion takeover of Karuna last December, which was driven by the potential of KarXT in schizophrenia as well as other disorders including Alzheimer’s psychosis and bipolar disorder and is due to complete in the first half of this year.
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