Acadia Manufacturing Growing Pains Delay Pimavanserin NDA A Second Time
This article was originally published in Pharmaceutical Approvals Monthly
Executive Summary
Company says delay is due to manufacturing scale-up work and does not reflect any change in Parkinson’s psychosis drug’s efficacy or safety profile. In tandem with the news, CEO Hacksell retired, replaced on interim basis by CFO Davis.
A second delay in the filing of an NDA for Parkinson’s psychosis candidate pimavanserin and the simultaneous retirement of CEO Uli Hacksell has resulted in a sell-off of Acadia Pharmaceuticals Inc. stock, but the biotech contends that the delay is due to manufacturing scale-up work and does not reflect any weakness in the compound’s efficacy or safety profile.
The San Diego firm revealed late March 11 that pimavanserin’s submission for psychosis related to Parkinson’s disease, to be branded Nuplazid if approved, now is planned for the second half of 2015. The previous target had been the first quarter of this year. Timelines for the drug were also pushed back in 2013 when the company had to re-design its pivotal trial program after an initial failure (Also see "Acadia’s Persistence With Pimavanserin In Parkinson’s Psychosis Pays Off" - Pink Sheet, 16 Apr, 2013.).
Acadia’s stock finished the day down 22% March 12 at $34.82. But analysts from Jefferies Equity Research and JMP Securities called the downturn a buying opportunity, as the fundamentals underlying the market potential of pimavanserin, a selective serotonin inverse agonist that targets 5-HT2A receptors, remain unchanged (Also see "Parkinson’s Disease Market Snapshot: A Wave Of Drugs For Symptoms" - Pink Sheet, 1 Dec, 2014.). The drug carries a "breakthrough" therapy designation for Parkinson's psychosis, and would be the first approval for the indication.
“While an unfortunate delay, this does not change our analysis of the market opportunity for Nuplazid, and we note that the market is largely generic and there is no pipeline competition on the horizon,” Jefferies analyst Thomas Wei wrote in a March 12 note.
JMP’s Jason Butler remained similarly bullish about pimavanserin’s eventual prospects, saying in a March 12 note that he is confident the delay is not due to any concerns or pushback from FDA.
“We are confident that the sole cause of the delay is the need to better prepare manufacturing quality and supply systems and we believe the probability of approval for Nuplazid is unchanged and remains high,” he said. “We continue to view the clinical benefit of the drug candidate as impressive and clearly differentiated from the limited treatment options currently available and highlight the scarcity value of this novel and high-quality neurology asset.”
On an investor call, Acadia claimed that the retirement of Hacksell, who also is exiting the board of directors but will remain a consultant to the firm for 18 months, was a separate situation from the NDA timing change. Chief Financial Officer Steve Davis steps in as interim CEO. Davis noted that although he only joined Acadia eight months ago, he brings more than 20 years of experience as a CEO and chief operating officer to his new responsibilities.
Issues In Transitioning From Clinical-Stage Company
Davis explained the delay in filing pimavanserin as due to a need to finish manufacturing and quality systems and procedures, which would be reviewed by FDA in connection with the NDA.
“Moving from a clinical-stage company to a commercial-stage company, as we are doing, requires building infrastructure to accommodate commercial-scale operations,” Davis told the call. “These systems include things such as robust quality-assurance systems, documentation and record-keeping systems, commercial-oriented Standard Operating Procedures, or SOPs, systems to monitor activities of third-party suppliers, and simply the management of materials through the supply chain.”
“Establishing the infrastructure I’ve described requires close coordination between our internal manufacturing resources, external third-party suppliers and the quality assurance functions within each organization,” he added. “Because these manufacturing and supply systems are subject to inspection as part of the NDA review process, it is an important that our systems be robust and ready for FDA review and of course for commercial launch.”
Davis acknowledged that investors would be disappointed with the delay, but said Acadia has realigned roles and responsibilities to “shore up deficiencies and position us for success.” Acadia is both expanding the roles of manufacturing consultants working with the company and hiring additional staff to enhance internal capabilities, he said.
“Just to be clear, this has nothing to do with pimavanserin itself. It has nothing to do with the formulation of the drug or synthesis of the drug,” the exec asserted. “This is a small molecule with a very straightforward synthetic group. This is simply a matter of having the correct processes and systems in place. We will do that. This is not the type of issue that prohibits or limits the approval of a drug once you have the appropriate systems in place. I think it's also very important to note that the change in submission timing is not a result of any change in Nuplazid’s clinical or safety profile, nor is it a result of any new interaction with the FDA.”
Jefferies’ analyst Wei suggested that the market’s strong negative reaction to the news may stem partly from the fact that Acadia did not indicate any such problems on its quarterly earnings call less than a month ago.
“Management noted that mistakes had been made, and that they have realized that more work needs to be done since the last earnings call on Feb 26,” he said. “We believe the drug does not require a complicated manufacturing process, and we believe that manufacturing is unlikely to prevent ultimate approval.”