CHMP Recommends EU Approval of DAYBUE® (trofinetide)
Acadia Pharmaceuticals Inc. has announced a significant regulatory milestone for its rare disease portfolio after the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion recommending the approval of DAYBU® (trofinetide) for the treatment of neurobehavioral symptoms associated with Rett syndrome in adults and children aged five years and older.
The favorable recommendation follows a re-examination procedure and marks an important step toward making the therapy available to patients across Europe. If the European Commission grants marketing authorization, DAYBU® would become the first medicine approved in the European Union specifically for the neurobehavioral symptoms of Rett syndrome, addressing a long-standing unmet medical need for patients and families affected by this rare neurological disorder.
The positive opinion also represents a major achievement for Acadia Pharmaceuticals as it continues to expand its global presence in rare neurological diseases and advance innovative therapies for conditions with limited treatment options.
A Major Milestone for Patients with Rett Syndrome
Rett syndrome is a rare, severe neurodevelopmental disorder that primarily affects girls and is caused in most cases by mutations in the MECP2 gene. Although affected children often appear to develop normally during the first months of life, they eventually experience a progressive loss of acquired skills, including speech, purposeful hand movements, and motor function.
The disorder is also characterized by a broad range of neurobehavioral symptoms that significantly affect communication, social interaction, cognition, emotional regulation, and daily functioning.
Families caring for individuals with Rett syndrome often face lifelong challenges, as the condition affects nearly every aspect of a patient’s physical, emotional, and cognitive development.
Despite decades of research, treatment options specifically targeting the neurobehavioral manifestations of Rett syndrome have remained extremely limited, particularly within Europe.
The CHMP’s positive opinion therefore represents an important advancement for the Rett syndrome community.
Re-Examination Results in Positive Regulatory Outcome
Acadia Pharmaceuticals explained that the favorable recommendation follows a formal re-examination process conducted by the European Medicines Agency.
Under EMA procedures, applicants may request a re-evaluation when an initial opinion raises concerns regarding an application. During this process, the submitted evidence undergoes an additional scientific review before the CHMP issues its final recommendation.
Following completion of this reassessment, the committee concluded that the available clinical evidence supports granting marketing authorization for DAYBU® for eligible adult and pediatric patients aged five years and older.
The positive recommendation now moves the application to the European Commission, which is responsible for issuing the final legally binding decision regarding approval throughout the European Union.
Potential First Approved Therapy in the European Union
If the European Commission follows the CHMP recommendation, DAYBU® would become the first therapy specifically approved within the European Union for treating the neurobehavioral symptoms of Rett syndrome.
Such approval would represent a historic milestone for the European rare disease community.
A centralized marketing authorization would allow the medicine to become available across all 27 European Union member states, as well as Iceland, Liechtenstein, and Norway, providing broader access for eligible patients throughout the region.
For many families, approval would mark the first time a medicine specifically developed to address core aspects of Rett syndrome becomes available through European healthcare systems.
Company Reaffirms Commitment to the Rett Community
Catherine Owen Adams, Chief Executive Officer of Acadia Pharmaceuticals, described the CHMP’s positive opinion as an important achievement in the company’s broader mission to improve treatment options for individuals living with rare neurological disorders.
She noted that patients across the European Union currently have no approved therapies specifically indicated for the neurobehavioral symptoms of Rett syndrome.
According to Adams, Acadia remains committed to bringing innovative treatments to patients and believes DAYBU® has the potential to make a meaningful difference in the lives of affected individuals, caregivers, and the broader Rett syndrome community.
She also expressed satisfaction with the outcome of the EMA re-examination process, describing it as an important step toward expanding access to the therapy across Europe.
Clinical Evidence Supports Regulatory Recommendation
The CHMP’s recommendation was based primarily on findings from the company’s Phase 3 LAVENDER™ clinical trial, which evaluated the efficacy and safety of DAYBU® in patients with Rett syndrome.
The study demonstrated statistically significant improvements across key clinical measures that assess the severity of symptoms associated with the disorder.
One of the primary endpoints involved the Rett Syndrome Behavior Questionnaire (RSBQ), a validated assessment tool designed to measure behavioral and neurological symptoms experienced by individuals with Rett syndrome.
Patients receiving DAYBU® showed clinically meaningful improvements on this scale compared with baseline assessments.
The study also demonstrated favorable outcomes using the Clinical Global Impression-Improvement (CGI-I) scale, an internationally recognized measure that evaluates overall clinical improvement as assessed by healthcare professionals.
Together, these findings provided evidence that treatment with DAYBU® may improve several of the core neurobehavioral symptoms that substantially affect daily functioning and quality of life.
Addressing a Significant Unmet Medical Need
The neurobehavioral manifestations of Rett syndrome extend far beyond developmental delay.
Patients frequently experience communication difficulties, repetitive hand movements, anxiety, irritability, social withdrawal, abnormal behaviors, and impaired cognitive functioning.
These symptoms can severely limit independence while placing considerable emotional, physical, and financial burdens on caregivers and families.
Because no medicines have previously been approved within the European Union specifically to treat these aspects of the disease, physicians have generally relied on supportive care and symptom management using medications developed for other neurological conditions.
Acadia believes DAYBU® offers the potential to directly address important features of Rett syndrome rather than simply managing individual symptoms.
If approved, the therapy could significantly expand available treatment options for clinicians caring for this rare patient population.
Rett Syndrome Europe Welcomes the Recommendation
The positive CHMP opinion has also been welcomed by patient advocacy organizations representing individuals affected by Rett syndrome.
Pedro Rocha, President of Rett Syndrome Europe, emphasized that families have waited decades for a therapy specifically approved to treat the neurobehavioral symptoms associated with the condition.
He noted that these symptoms affect nearly every aspect of daily life, influencing communication, independence, education, family relationships, and overall quality of life.
According to Rocha, the committee’s recommendation provides renewed hope for thousands of individuals living with Rett syndrome throughout Europe, as well as for their parents, caregivers, and support networks.
The recommendation also reflects years of advocacy by patient organizations seeking greater research investment and improved access to innovative therapies.
European Commission Review Is the Final Regulatory Step
Although the CHMP’s recommendation represents a major regulatory milestone, the marketing authorization process is not yet complete.
The application will now be reviewed by the European Commission, which makes the final decision regarding approval of medicines within the European Union.
The Commission generally considers the scientific recommendation issued by the CHMP before adopting its final legally binding decision.
Acadia expects the review to conclude within the coming months.
Should approval be granted, DAYBU® would receive centralized marketing authorization valid throughout all EU member states and participating countries within the European Economic Area.
This would allow national healthcare systems to begin evaluating reimbursement and patient access pathways according to local regulations.
Expanding Acadia’s Global Rare Disease Strategy
The positive CHMP opinion further strengthens Acadia Pharmaceuticals’ strategy of expanding innovative therapies for rare neurological disorders across international markets.
The company has increasingly focused on developing treatments that address diseases with substantial unmet medical needs, particularly conditions affecting the central nervous system where approved therapeutic options remain limited.
Securing European authorization for DAYBU® would represent an important addition to Acadia’s global commercial portfolio while reinforcing its commitment to supporting patients living with rare, complex neurological disorders.
The company continues working closely with regulatory authorities, healthcare professionals, patient organizations, and caregivers to improve awareness, diagnosis, and access to emerging therapies.
The CHMP’s positive opinion marks a significant step toward making DAYBU® available to patients with Rett syndrome across Europe. If the European Commission grants final approval, the therapy would become the first medicine specifically authorized in the European Union for the treatment of neurobehavioral symptoms associated with this devastating rare disorder.
Supported by positive Phase 3 clinical data and renewed regulatory confidence following the re-examination process, DAYBU® has the potential to transform the treatment landscape for Rett syndrome by offering patients and clinicians a targeted therapeutic option where none currently exists. For thousands of families living with the daily challenges of Rett syndrome, the anticipated European decision represents more than a regulatory milestone—it offers the possibility of meaningful progress in addressing one of the condition’s most burdensome and life-altering aspects.
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
Symptoms of Rett syndrome may also include development of hand stereotypes, 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 DAYBU ®
DAYBU ® (trofinetide) is a synthetic analogue of the N-terminal tripeptide of insulin-like growth factor 1.
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.
