Acadia Pharmaceuticals Inc. CEO Stephen Davis told BioWorld Today that the firm has "done everything you would want to do to be prepared for a successful launch" of Nuplazid (pimavanserin) to treat psychosis associated with Parkinson's disease (PDP), and is approaching the launch in a "pharma-esque" manner.

"One of the things they do typically really well is understand the marketplace and the dynamics," he said, and San Diego-based Acadia has conducted extensive market research, put in place a disease-awareness program, and built a strong team.

The San Diego-based firm submitted its new drug application (NDA) after delays that troubled some on Wall Street. Although the NDA is "what people primarily focus on and what comes top of mind," Acadia also had to prepare for clinical and manufacturing inspections related to quality assurance, Davis said. "There are a certain amount of enhancements that you need to make to your system in able to be commercial-ready," he said. "We frankly just needed more time on just the manufacturing-quality front, to get that system up and running and sufficiently robust to be prepared for commercial-scale manufacturing and, importantly, to be ready for these inspections that we very likely will have with the FDA."

A phase II trial is under way in Alzheimer's disease psychosis (ADP), too. Acadia said it believes the selective serotonin inverse agonist, which preferentially targets 5-HT2A receptors, could dodge many of the debilitating side effects of existing antipsychotics, none of which is approved for use in PDP or ADP patients.

"We've shown very strong anti-psychotic activity in PDP, but we've also shown anti-psychotic activity in schizophrenia," where more testing will be done as well, said Davis, who has been with Acadia for a little over a year and was just named permanently to his position after serving as interim CEO. "The underlying pathophysiology of those diseases of course is very different, but we're not treating the underlying disease, we're treating a symptom, and the symptoms are actually very similar," he said. "We have a situation where the field has not advanced dramatically in more than a couple of decades," and Nuplazid is "totally different from every anti-psychotic on the market today," especially with regard to the safety profile.

Not only are available anti-psychotics not recommended for PDP and ADP patients, but they also have black-box warnings on the labels because they increase mortality in those populations. Even short of death, consequences are anything but ideal. "People are more familiar with this in PDP, but they don't fully appreciate it sometimes in ADP," Davis said. "In PDP, taking these anti-psychotics actually interferes with the treatments they're receiving to treat the motor symptoms, [which are] the primary symptoms you have in Parkinson's disease." In ADP, when taken off label, such drugs "actually worsen cognition" by a factor equal to one year's disease advance, he said. "They're typically used only when patients get so severe, they just have to have something."


Cowen and Co. analyst Ritu Baral, reporting Aug. 27 on a meeting with Acadia management, wrote that execs "indicated the screen failure rate of the ongoing phase II trial in ADP has been slightly higher than expected, but that they have no intention of relaxing the stringent entry criteria of the trial. While the entry criteria of the single-center trial have not been formally released, Acadia did indicate that enrollment focuses on advanced patients that have more severe ADP, allowing for potential greater treatment effect. While enrollment rates have been variable, the company believes this is in no way reflective of the ADP market opportunity, which they believe to be 3-4 times the size of the PDP opportunity."

Signing up patients in the ADP trial is "not like enrolling another statin" experiment, CEO Davis noted. "You never know exactly how these enrollment curves will go," and the process is "taking a little bit longer than the company originally imagined it might," though this has nothing to do with entry criteria or logistics. "You want to make sure when you enroll these studies that you don't compromise in any way," he said, and predicted completion of enrollment in the first half of next year.

Meanwhile, Acadia's "strategy is very clear," Davis said. "We plan to launch this drug independently in the U.S." and consider partnerships in other territories. The firm has "significant access to capital," he said. Some company watchers have speculated about when the next financing might come, a habit "not specific to Acadia," he said. "Biotech companies consume capital until they get to a point where they're cash flow-positive, and so investors are always trying to anticipate when a financing will come, because it gives them an opportunity to acquire a larger block of stock than they might be able to acquire readily in the marketplace. [Biotech firms] are relatively thinly traded frequently. What you're seeing is nothing more than that."

The FDA has given Nuplazid breakthrough designation and Acadia has asked for priority review. "It's not guaranteed but is very common" to get one after the other, Davis pointed out.

J.P. Morgan analyst Cory Kasimov, in an email alert, called the NDA news "welcome relief for the story, and [we] are not surprised by this morning's initial move" in the stock price. "Bottom line, we continue to see Acadia as an intriguing name in the space equipped with a differentiated asset targeting high-unmet-need indications."

Aegis Capital Robert LeBoyer said the NDA filing "is early in our expected range. If priority review is granted, approval could come as early as March 2016. This would be an important development that could lead to product launch much earlier than our estimates, representing additional upside from our price target," which is $54, he wrote in a research report. The FDA has 60 days to review the NDA and decide about priority review.

The company's shares (NASDAQ:ACAD) closed Thursday at $39.13, up $1.06.