March 2, 2026 — Leads & Copy — Acadia Pharmaceuticals Inc. (Nasdaq: ACAD) has been informed by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) that 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 plans to request a re-examination of the opinion after reviewing the CHMP’s grounds for refusal.
The CHMP issued the refusal despite the pivotal LAVENDERTM trial successfully meeting its co-primary and key secondary endpoints. The CHMP’s grounds for refusal were based on perceived deficits including the treatment effect observed with trofinetide after 12 weeks, the study not capturing all core symptoms of Rett syndrome, and assessment of longer-term outcomes being influenced by patient discontinuations over time.
Catherine Owen Adams, Acadia’s Chief Executive Officer, said that while the company is disappointed by the CHMP’s recommendation to refuse approval, they continue to be encouraged by the meaningful benefits trofinetide has demonstrated for people living with Rett syndrome. She also said that the strong engagement and positive feedback they have seen from patients, caregivers, and clinicians in the Rett community reinforce their belief in the treatment’s clinical value, and that they remain committed to working constructively with EU regulators to explore next steps and to bring this therapy to patients.
Markus Schulze, caregiver and member of the Rett Syndrome Society Nordrhein-Westfalen from Germany, said that their 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. He also said that it is their 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.
Rett syndrome is a rare, complex, neurodevelopmental disorder and occurs in approximately one of every 10,000 to 15,000 female births worldwide. 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. Rett syndrome is typically caused by a genetic mutation on the MECP2 gene. 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.
Features of Rett syndrome may also include development of hand stereotypies, such as hand wringing and clapping, and gait abnormalities. Most individuals living with Rett syndrome typically live into adulthood and require intense round-the-clock care.
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.
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.
Source: Acadia Pharmaceuticals
