Acadia Pharmaceuticals Announces Plan to Request Re-Examination Following Negative CHMP Opinion for Trofinetide for the Treatment of Rett Syndrome

SAN DIEGO--(BUSINESS WIRE)--Acadia Pharmaceuticals Inc. (Nasdaq: ACAD) today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) informed the company it has formally adopted a negative opinion regarding the Marketing Authorization Application for trofinetide for the treatment of Rett syndrome in patients two years of age and older. Acadia has reviewed the CHMP grounds for refusal in detail and intends to request a re-examination of the opinion.

While the pivotal LAVENDER^TM trial successfully met its co-primary and key secondary endpoints, the CHMP issued a refusal based on perceived deficits including: the treatment effect observed with trofinetide after 12 weeks, while measurable, was viewed as limited in magnitude; the study did not capture all core symptoms of Rett syndrome; and that assessment of longer‑term outcomes was influenced by patient discontinuations over time. Acadia believes this feedback provides important information as it considers the intended re-examination.

“While we are disappointed by the CHMP’s recommendation to refuse approval, we continue to be encouraged by the meaningful benefits trofinetide has demonstrated for people living with Rett syndrome,” said Catherine Owen Adams, Acadia’s Chief Executive Officer. “The strong engagement and positive feedback we have seen from patients, caregivers, and clinicians in the Rett community reinforce our belief in the treatment’s clinical value. We remain committed to working constructively with EU regulators to explore next steps and to bring this therapy to patients.”

“Our family and others who play an important role in the delivery of care know first-hand the challenges that individuals living with Rett syndrome face every day,” said Markus Schulze, caregiver and member of the Rett Syndrome Society Nordrhein-Westfalen from Germany. “It is our hope that this important therapy will be approved to help the EU Rett community better navigate life with Rett syndrome.”

Trofinetide is approved in the United States, Canada and Israel, where it represents the first and only treatment approved for Rett syndrome.

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 when the child loses 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 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 brain plasticity, and the deficits in synaptic function may be associated with Rett manifestations.^4-6

Features 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. 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 or 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 to 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, 2025 as well as our subsequent filings with the Securities and Exchange Commission from time to time. 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:e000717.
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 Med Econ. 2023;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.