Ouch! Acadia's non-opioid painkiller flunks midphase test, weakening a potential rival to Vertex

Acadia Pharmaceuticals’ hopes of chasing Vertex into phase 3 have taken a big hit. Weeks after Vertex’s non-opioid painkiller chalked up a midphase win, Acadia’s rival candidate has failed in a similar setting, leaving its future in acute pain in doubt.

The Acadia trial randomized 239 patients undergoing bunion removal on one foot to receive placebo or one of two regimens of ACP-044, an oral small molecule the company believes modulates redox pathways involved in pain signaling. Participants received the first dose prior to surgery and continued with the treatment for four days in total.

Compared to placebo, neither ACP-044 regimen had a statistically significant effect on cumulative pain intensity scores over 24 hours, causing the study to miss its primary endpoint. The failure left Acacia with a trend favoring the four times daily ACP-044 regimen as the strongest evidence that the drug works.

In the cohort of patients who received ACP-044 every six hours, a 10.5-point improvement in the primary endpoint was seen over placebo but the difference fell short of statistical significance. The p-value was 0.1683. Acadia also reported numerical, but not statistical, improvements in pain scores at 48 hours and 72 hours. The company is yet to share data on the cohort of patients who took ACP-044 once a day.

Acadia is still deciding on the next steps. In a statement, Acadia CEO Steve Davis said the company is still analyzing “the totality of the data to best determine whether further development in acute pain is appropriate.” Investors responded by sending Acadia’s stock down 5% to $21 in after-hours trading. The muted response potentially reflects the fact that Acadia’s prospects rest more on its ability to expand the use of Nuplazid, both in Parkinson’s and new indications, and to get its Rett syndrome asset to market. 

The setback comes weeks after Vertex, no stranger to failure in pain R&D, reported that its latest Nav1.8 inhibitor reduced the pain of patients undergoing bunion removal in the 48 hours after the procedure. With a phase 2 trial in tummy-tuck patients hitting at the same time, Vertex is planning to move into a pivotal trial in the second half of the year.

Acadia’s best chance of following Vertex into phase 3 may now lie in chronic pain. A phase 2 trial in pain associated with osteoarthritis of the knee got underway last year, putting Acadia on track to complete the study in the first half of 2023.

How ACP-044 performs in that trial will go some way to determining how much it pays for the molecule.  Acadia picked up the drug candidate for $52.5 million, primarily in stock, in its 2020 takeover of CerSci Therapeutics. The deal is back loaded, with CerSci shareholders in line to receive up to $887 million in development, commercialization and sales milestones if the acquired assets are successful.

Mizuho analyst Vamil Divan said the news of ACP-044’s trial failure was expected to heighten anticipation for the upcoming FDA advisory committee meeting to discuss Nuplazid in Alzheimer’s disease psychosis (ADP), as investors look for additional growth drivers for Acadia.

“We remain cautious on Nuplazid getting approved in ADP without a new clinical trial, and that drives our Neutral rating on [Acadia] shares,” Divan said in a note.

Editor's note: The article was amended at 11:55am on April 19, 2022 to include analyst commentary.