Acadia Pharmaceuticals Provides Update on Regulatory Submission for Trofinetide for the Treatment of Rett Syndrome in the European Union

- Company expects to receive a negative opinion following oral explanation feedback and intends to request re‑examination upon review of formal adoption.

SAN DIEGO--(BUSINESS WIRE)--Acadia Pharmaceuticals Inc. (Nasdaq: ACAD) today announced that the Company was informed by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) of a negative trend vote on its Marketing Authorization Application (MAA) for trofinetide for the treatment of Rett syndrome, following its recent CHMP oral explanation. Subject to the outcome of the CHMP vote in February, Acadia intends to request a re-examination of the opinion by the CHMP upon its formal adoption.

“While the negative trend vote is disappointing and not what we hoped for, we believe the strong data that supported the approval of trofinetide for the treatment of Rett syndrome in the United States, Canada, and Israel speak to the meaningful benefits that trofinetide can deliver,” said Catherine Owen Adams, Chief Executive Officer. “We now have more than 1,000 patients on active treatment globally, from newly diagnosed 2-year-olds to adults who have lived with their disease for decades. Our ongoing real-world experience study in the U.S. continues to show outcomes that closely mirror the impact observed in rigorous randomized clinical trials conducted across a broad age range. We look forward to working with the EMA and other stakeholders to advance trofinetide as an important potential treatment option in the EU. Our commitment to the Rett syndrome community in the EU remains steadfast, and we are fully dedicated to making trofinetide available to individuals and families who urgently need a new therapeutic option.”

Pursuant to EU legislation, an applicant has the right to request a re-examination of a CHMP opinion within 15 calendar days of receipt of the opinion, followed by submission of the grounds for the request for re-examination within 60 calendar days of receipt of the opinion. The CHMP has up to 60 days after receipt of these grounds to re-examine its opinion.

About Rett Syndrome

Rett syndrome is a rare, complex, neurodevelopmental disorder and occurs in approximately one of every 10,000 to 15,000 female births worldwide.^1-3 A child with Rett syndrome generally exhibits an early period of apparently normal development until six to 18 months, when many of their skills seem to slow down or stagnate. This is typically followed by a regression phase (general duration few weeks) when the child loses for example acquired communication skills and purposeful hand use. The child may then experience a plateau period in which they could show mild recovery in cognitive interests, but body movements and other disease features may remain severely diminished. As they age, those individuals living with Rett may continue to experience a stage of motor deterioration which can last the rest of the patient’s life.² Rett syndrome is typically caused by a genetic mutation on the MECP2 gene.⁴ In preclinical studies, deficiency in MeCP2 function is thought to lead to impairment in synaptic communication, and the deficits in synaptic function may be associated with Rett manifestations.^4-6 Symptoms of Rett syndrome may also include development of hand stereotypies, such as hand wringing and clapping, and gait abnormalities.⁷ Most individuals living with Rett syndrome typically live into adulthood and require intense round-the-clock care.^1,8

About Trofinetide

Trofinetide is a synthetic analog of the N-terminal tripeptide of insulin-like growth factor.¹ The mechanism by which trofinetide exerts therapeutic effects in patients with Rett syndrome is unknown. In animal studies, trofinetide has been shown to increase branching of dendrites and synaptic plasticity signals.⁹

About Acadia Pharmaceuticals

Acadia is committed to turning scientific promise into meaningful innovation that makes the difference for underserved neurological and rare disease communities around the world. Our commercial portfolio includes the first and only FDA-approved treatments for Parkinson’s disease psychosis and Rett syndrome. We are developing the next wave of therapeutic advancements with a robust and diverse pipeline that includes mid- to late-stage programs in Alzheimer’s disease psychosis and Lewy body dementia psychosis, along with earlier-stage programs that address other underserved patient needs. At Acadia, we’re here to be their difference. For more information, visit us at acadia.com and follow us on LinkedIn and X.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include all statements other than statements of historical fact and can be identified by terms such as “may,” “will,” “should,” “could,” “would,” “intends”, “expects,” “plans,” “anticipates,” “believes,” “estimates,” “projects,” “predicts,” “potential,” “guidance,” “continue” and similar expressions (including the negative thereof) intended to identify forward-looking statements. Forward-looking statements contained in this press release, include, but are not limited to, statements about our plan to pursue the re-examination process, our beliefs about the benefits of trofinetide, and our commitment to making trofinetide available in the European Union. Forward-looking statements are subject to known and unknown risks, uncertainties, assumptions and other factors that may cause our actual results, performance or achievements to differ materially and adversely from those anticipated or implied by our forward-looking statements. Such risks, uncertainties and other factors include, but are not limited to, the inherent uncertainty regarding development of product candidates, including the outcome of the CHMP vote and the results of any re-examination of the CHMP’s formal opinion; our dependency on the continued successful commercialization of our products and our ability to maintain or increase sales of our products; our ability obtain necessary regulatory approvals to commercialize our products and product candidates; if and when approved, market acceptance of our products and our ability to continue to stay in compliance with applicable laws and regulations. Given the risks and uncertainties, you should not place undue reliance on these forward-looking statements. For a discussion of these and other risks, uncertainties and other factors that may cause our actual results, performance or achievements to differ, please refer to our annual report on Form 10-K for the year ended December 31, 2024 as well as our subsequent filings with the Securities and Exchange Commission from time to time, including our quarterly report on Form 10-Q for the quarter ended September 30, 2025. The forward-looking statements contained herein are made as of the date hereof, and we undertake no obligation to update them after this date, except as required by law.

References
^1	Fu C, Armstrong D, Marsh E, et al. Consensus guidelines on managing Rett syndrome across the lifespan. BMJ Paediatrics Open. 2020; 4:1-14.
^2	Kyle SM, Vashi N, Justice MJ. Rett syndrome: a neurological disorder with metabolic components. Open Biol. 2018; 8:170216.
^3	May DM, Neul JL, Satija A, et al. Real-world clinical management of individuals with Rett syndrome: a physician survey. J of Med Econ. 26(1), 1570–1580.
^4	Amir RE, Van den Veyver IB, Wan M, et al. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat Genet. 1999; 23(2):185-188.
^5	Fukuda T, Itoh M, Ichikawa T, et al. Delayed maturation of neuronal architecture and synaptogenesis in cerebral cortex of Mecp2-deficient mice. J Neuropathol Exp Neurol. 2005; 64(6):537-544.
^6	Asaka Y, Jugloff DG, Zhang L, et al. Hippocampal synaptic plasticity is impaired in the Mecp2-null mouse model of Rett syndrome. Neurobiol Dis. 2006; 21(1):217-227.
^7	Neul JL, Kaufmann WE, Glaze DG, et al. Rett syndrome: revised diagnostic criteria and nomenclature. Ann Neurol. 2010; 68(6):944-950.
^8	Tarquinio DO, Hou W, Neul JL, et al. The changing face of survival in Rett syndrome and MECP2-related disorders. Pediatr Neurol. 2015; 53(5):402-411.
^9	Acadia Pharmaceuticals Inc., Data on file. Study Report 2566-026. 2010.