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

Key Terms

committee for medicinal products for human use regulatory

The Committee for Medicinal Products for Human Use is the expert scientific panel within the European medicines regulator that assesses whether medicines for people are safe, effective and of acceptable quality, and issues formal opinions used in the drug-approval process. Its assessments act like a gatekeeper or safety inspector for entering the European market, so the committee’s opinion can materially affect a drug’s commercial prospects, regulatory risk and a company’s stock valuation.

chmp regulatory

The CHMP is the European Medicines Agency’s expert panel that evaluates whether a medicine for people should be recommended for approval across the EU. Think of it as a technical review board whose positive or negative opinion strongly affects a drug maker’s ability to sell a product in the European market, shaping potential revenues, regulatory risk and investment timelines for companies developing or marketing therapies.

european medicines agency regulatory

The European Medicines Agency is the central drug regulator that evaluates and authorizes medicines for use across the European Union and related countries, similar to a referee or safety inspector who checks that a medicine is safe and effective before it can be sold. Its decisions matter to investors because approvals, rejections, or safety warnings directly affect a drug maker’s ability to sell products, generate revenue, and face legal or reputational risks, which in turn influence stock value.

marketing authorization application regulatory

A marketing authorization application is a formal request submitted to a government regulator asking permission to sell a prescription medicine or medical product in a country or region. Think of it like asking for a business license after showing evidence the product is safe and works; investors care because approval determines whether the product can generate sales, how soon revenue starts, and how much regulatory risk and uncertainty remains.

rett syndrome medical

A rare genetic disorder that disrupts normal brain development in young children, most commonly girls, leading to slowed growth, loss of purposeful hand use, repetitive hand movements, motor problems, speech loss, and cognitive and breathing irregularities. Investors watch it because its severity and few treatment options create clear medical need and potential markets for therapies; think of it as a broken traffic signal in the brain that, if fixed, could restore many downstream functions.

mecp2 gene medical

A gene that provides instructions for a protein acting like a master switch in brain cells, helping regulate the activity of many other genes during development. Mutations in this gene can lead to severe neurodevelopmental disorders, so it is a major target for diagnostics and therapeutic research; investors watch such targets because successful tests, drugs, or gene therapies can drive significant value for biotech companies.

synaptic plasticity medical

Synaptic plasticity is the brain’s ability to change the strength and number of connections between nerve cells so learning, memory and recovery from injury can occur; think of it as turning up or down volume knobs on the wiring of the brain or forging new walking paths through a forest. It matters to investors because many drugs, devices and diagnostic tests aim to enhance or measure these connection changes as a way to treat cognitive and neurological disorders, so evidence of effects on synaptic plasticity can drive clinical value, regulatory interest and commercial potential.

dendrites medical

Dendrites are the branching extensions of nerve cells that receive and combine incoming signals from other cells, like antennae gathering different radio stations and passing a blended signal to the cell body. Investors should care because many neurological diseases and treatments affect these structures; evidence that a drug, device or test protects, restores or measures dendritic function can signal a meaningful biological effect, influence regulatory approval and shape commercial potential.

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.

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