Acadia Pharmaceuticals Inc. (Nasdaq: ACAD) today announced top-line results from a Phase 2 randomized, double-blind, placebo-controlled clinical trial evaluating the efficacy and safety of ACP-044 for acute pain following bunionectomy surgery. The primary endpoint, a comparison of cumulative pain intensity scores over 24 hours between the ACP-044 1600 mg once daily, ACP-044 400 mg four times daily and placebo treatment arms, was not met.

A trend favoring the ACP-044 400 mg once every six hours treatment group was observed on the primary endpoint, a difference of -10.5 points compared to placebo (p = 0.1683; effect size = 0.219). These numerical trends were consistently better than placebo, but not statistically significant, at 48 hours and 72 hours.

“We are disappointed that the ACP-044 bunionectomy study did not meet its primary endpoint, especially given the significant need for novel, non-opioid treatment options for postsurgical pain. We will continue to analyze the totality of the data to best determine whether further development in acute pain is appropriate,” said Steve Davis, Chief Executive Officer. “We’d like to thank the study participants as well as the investigators and staff who contributed to this study.”

Most adverse events were mild-to-moderate and there were no serious adverse events related to ACP-044. Fewer patients discontinued treatment in the ACP-044 arms than in the placebo group.

Acadia is currently evaluating ACP-044 in an ongoing study in osteoarthritis, a model of chronic pain, which is expected to complete in the first half of 2023.

About Phase 2 Proof-of-Concept Bunionectomy Study

The Phase 2 clinical trial design, evaluating the safety and efficacy of the investigational drug ACP-044 for the treatment of acute postoperative pain following orthopedic surgery (bunionectomy), was a multicenter, randomized, double-blind, parallel-group, placebo-controlled clinical trial involving 239 patients undergoing bunion removal on one foot. Patients were randomized to one of the following three groups: 1600 mg of ACP-044 administered once daily (n=78), 400 mg every six hours (n=81), or placebo (n=80). Patients were first dosed prior to surgery and continued treatment for a total of four days. Patients self-reported their pain intensity using the Numeric Rating Scale (NRS), which scores pain on a scale of 0-10.

About ACP-044

ACP-044 is a non-opioid, novel, first in class, redox modulator investigational drug in development for the treatment of acute and chronic pain.¹ ACP-044 is an orally bioavailable small molecule with minimal brain distribution that is believed to function as a redox modulator of reactive oxygen species such as peroxynitrite. Reactive oxygen species arise from tissue injury and inflammation and are thought to intensify pain through a variety of different pathways.^2,3,4,5,6 ACP-044’s mechanism of action is believed to modulate redox pathways involved in pain signaling by reducing increased levels of reactive oxygen and nitrogen species such as peroxynitrite.¹ Downstream effects of increased reactive oxygen and nitrogen species levels may result in peripheral and central nerve sensitization, cytotoxicity, inflammation, and pain.^2,3,4,7 Redox modulation represents a novel and promising approach to acute and chronic pain management. ^2,3,4,5,6

About Acute Postoperative Pain

Pain is a major healthcare issue, with high prevalence, significant patient burden and substantial economic impact.⁸ A high unmet need remains in postoperative pain with more than 50 million surgical cases in the U.S. annually and approximately 75% of patients reporting postoperative pain as moderate, severe, or extreme. ^9,10

Currently, opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) are the leading treatment options for acute postoperative pain.¹¹ Opioid overdose is the leading cause of death in the U.S. for people aged 18 to 45 years and in 2021, led to an average of 128 overdose deaths each day, per CDC estimates. As such, there is a great need for additional effective and safe treatment options as part of a multimodal treatment strategy.

About Acadia Pharmaceuticals

Acadia is advancing breakthroughs in neuroscience to elevate life. For more than 25 years we have been working at the forefront of healthcare to bring vital solutions to people who need them most. We developed and commercialized the first and only approved therapy for hallucinations and delusions associated with Parkinson’s disease psychosis. Our late-stage development efforts are focused on treating psychosis in patients with dementia, the negative symptoms of schizophrenia and Rett syndrome. Our early-stage development efforts are focused on novel approaches to pain management, cognition and neuropsychiatric symptoms in central nervous system disorders. For more information, visit us at www.acadia-pharm.com and follow us on LinkedIn and Twitter.

Forward-Looking Statements

Statements in this press release that are not strictly historical in nature are forward-looking statements. These statements include but are not limited to statements regarding the timing of future events. These statements are only predictions based on current information and expectations and involve a number of risks and uncertainties. Actual events or results may differ materially from those projected in any of such statements due to various factors, including the risks and uncertainties inherent in drug development, approval and commercialization. For a discussion of these and other factors, please refer to Acadia’s annual report on Form 10-K for the year ended December 31, 2021 as well as Acadia’s subsequent filings with the Securities and Exchange Commission. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. This caution is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. All forward-looking statements are qualified in their entirety by this cautionary statement and Acadia undertakes no obligation to revise or update this press release to reflect events or circumstances after the date hereof, except as required by law.

¹ Acadia. Data on file. 2021.

² Grace PM, Gaudet AD, Staikopoulos V, Maier SF, Hutchinson MR, et al. Nitroxidative signaling mechanisms in pathological pain. Trends Neurosci. 2016;39:862-879.

³ Zahan OM, Serban O, Gharman C, Fodor D. The evaluation of oxidative stress in osteoarthritis. Med Pharm Rep. 2020;93:12-22.

⁴ Fraunbeger EA, Scola G, Laliberte VLM, Duong A, Andreazza AC. Redox modulations, antioxidants, and neuropsychiatric disorders. Oxid Med Cell Longev. 2016;2016:4729192.

⁵ Janes K, Neumann WL, Salvemini D. Anti-superoxide and anti-peroxynitrite strategies in pain suppression. Biochim Biophys Acta. 2012;1822:815-821.

⁶ Little JW, Doyle T, Salvemini D. Reactive nitroxidative species and nociceptive processing: determining the roles for nitric oxide, superoxide, and peroxynitrite in pain. Amino Acids. 2012;42:75-94.

⁷ Rosenberger DC, Blechschmidt V, Timmerman H, Wolff A, Treede RD. Challenges of neuropathic pain: focus on diabetic neuropathy. J Neur Transmis. 2020;127:589-624.

⁸ Duenas M, Ojeda B, Salazar A, Mico JA, Faille I. A review of chronic pain impact on patients, their social environment and the health care system. J Pain Res. 2016;9:457-467.

⁹ ORManager.com; Can your hospital survive ASC, Aug 2020; https://www.ormanager.com/can-hospital-survive-growing-dominance-ascs/

¹⁰ Chou R, Gordon et al Management of Postoperative Pain: A Clinical Practice Guideline J Pain. 2016 Feb;17(2):131-57. doi: 10.1016/j.jpain.2015.12.008.

¹¹ Wilson N, Karise M, Seth P, Smith H IV, Davis NL. Drug and Opioid-Involved Overdose Deaths — United States, 2017–2018. Murkily Rep 2020;69:290–297.

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