Acadia to challenge negative opinion on Daybue approval in EU
European committee says data do not sufficiently demonstrate benefits
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Acadia Pharmaceuticals will request a reexamination of a negative opinion recommending against approval of trofinetide, its oral therapy for Rett syndrome, in the European Union (EU). The therapy is already approved in the U.S., Canada, and Israel under the name Daybue.
The opinion was issued by the Committee for Medicinal Products for Human Use (CHMP), the branch of the European Medicines Agency responsible for evaluating new drugs and recommending whether they should be approved or not in the EU. Final authorization is granted by the European Commission, which typically follows the CHMP’s recommendations.
Acadia submitted its application seeking EU approval of trofinetide last year. Before the formal opinion was issued, the company had been orally informed of a negative trend vote on the application, meaning the CHMP was unlikely to recommend approval of the therapy. The committee has now formally concluded that the available clinical data do not sufficiently demonstrate the therapy’s benefits in patients ages 2 and older with Rett syndrome.
“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,” Catherine Owen Adams, Acadia’s CEO, said in a company press release. “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.”
The company said it has reviewed the committee’s reasoning and intends to ask the CHMP to reexamine the application. Under EU regulations, drug developers have 15 days after receiving a formal opinion from the CHMP to request such a reexamination. The company would then have about two months to submit detailed reasons supporting its request, after which the committee would have roughly two months to reassess its decision.
“We remain committed to working constructively with EU regulators to explore next steps and to bring this therapy to patients,” Adams said.
Approvals in US, elsewhere based on clinical trials
Trofinetide, sold as Daybue, became the first treatment approved in the U.S. for Rett syndrome in 2023. The therapy was approved in Canada the following year, and more recently, Acadia announced its approval in Israel. In all three countries, the therapy is indicated for Rett patients ages 2 and older.
Data from several clinical trials supported these approvals. A Phase 3 LAVENDER clinical trial (NCT04181723), which tested trofinetide given twice daily for 12 weeks against a placebo in girls with Rett ages 5 to 20, found that the therapy significantly improved measures of neurobehavioral symptoms severity and overall health compared with a placebo. Participants in LAVENDER were then followed in two extension trials — LILAC-1 (NCT04279314) and LILAC-2 (NCT04776746) — which showed that improvements in these measures were maintained over time.
In a separate study, dubbed DAFFODIL (NCT04988867), which evaluated trofinetide in girls as young as 2, the therapy was found to improve measures of overall health and quality of life, with notable benefits in communication, eye contact, and hand use. Data from real-world use of trofinetide in the U.S. have also shown results generally consistent with those seen in clinical trials.
Despite these findings, the CHMP concluded the available data were insufficient to support trofinetide’s approval in the EU. Specifically, while the pivotal LAVENDER trial met its main and key secondary goals, regulators considered the treatment effect observed after 12 weeks of therapy, although measurable, to be relatively modest.
The committee also noted that the study did not assess all core Rett symptoms and that interpretation of long-term outcomes was influenced by patient dropouts during follow-up.
Acadia said the committee’s feedback will help guide its request for reexamination.
“Our family and others who play an important role in the delivery of care know [firsthand] the challenges that individuals living with Rett syndrome face every day,” said Markus Schulze, caregiver and member of the Rett Syndrome Society Nordrhein-Westfalen in Germany. “It is our hope that this important therapy will be approved to help the EU Rett community better navigate life with Rett syndrome.”
