Shares of San Diego-based Acadia Pharmaceuticals $ACAD shot up this morning after the company scored a success in a mid-stage study of its 5-HT2A -targeting drug Nuplazid (pimavanserin) in Alzheimer’s disease psychosis. But the biotech also had to face off against some expert opinion that was not in the least bit impressed by the results, especially factoring in a failed secondary endpoint that forced shares to slide back in the backlash.
Acadia’s drug — already approved for Parkinson’s disease psychosis — hit the primary endpoint in the mid-stage test. Using the NPI-NH Psychosis score, investigators tracked a 3.76 point improvement in psychosis at week 6 compared to a 1.93 point improvement for placebo, a statistically significant response. There were 181 patients enrolled in the study.
While much of the field is focused on either amyloid beta or tau, two toxic proteins that may trigger the Alzheimer’s, Acadia is focused on treating symptoms of the disease. Already pegged as a likely blockbuster, a new approval for Alzheimer’s could significantly expand this drug’s market reach, though the biotech has some ways to go before it can make a start.
One big problem for Acadia: Their drug failed to hit an important milestone on the psychosis score at week 12. In their 8-K, filed today, the company concedes the failure, noting: “On the secondary endpoint of mean change in NPI-NH Psychosis score at week 12, pimavanserin maintained the improvement on psychosis observed at the week six primary endpoint, but did not statistically separate from placebo.”
Alfredo Fontanini, an associate professor of neurobiology at Stony Brook University School of Medicine, was not impressed, tweeting that “this is not a signal finding trial, we know Pima affects hallucinations, point is can it sustain it at 12 weeks in ADP? No, ergo fail.”
Paul Matteis at Leerink also raised some thorny questions about the drug’s future. He wrote:
(T)his wasn’t a free call option in our view, but in any case we expect the shares to trade meaningfully higher today on the news as the ADP market and the AD agitation markets are very large. Nonetheless, looking ahead, we note that the benefit in this study is smaller than that seen in PDP, and it is unclear (1) whether or not ACAD can use the NPI psychosis score as a Ph 3 endpoint (should it decide to advance the program), (2) whether this result, which was generated at a set of nursing homes affiliated with the King’s College of London, is replicable across a larger number of clinical centers, and (3) what kind of safety database the FDA will require (we’d expect it to be large, given the agency’s current approach to labeling risks) to approve an anti-psychotic in Alzheimer’s.
Those questions began to influence investors’ attitudes early today. Acadia’s stock, which initially spiked 50%, was up only 13% after the market opened.
Nuplazid won FDA approval last spring, but only after regulators expressed their safety concerns, noting a distinct increase in the number of deaths as well as the rate of adverse events among the patients taking the drug compared to the control arm of the study — even if there was no obvious clue what was triggering those events.
“Alzheimer’s disease patients suffer from a number of debilitating symptoms, of which psychosis carries a poor prognosis and is associated with earlier placement into nursing homes,” said Steve Davis, Acadia’s President and Chief Executive Officer. “Data from the -019 Study provide solid evidence that pimavanserin can improve psychosis in another major neurological disorder and provide strategic momentum for the further development of pimavanserin to address the needs of AD Psychosis patients.”
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