Acadia Pharmaceuticals has not been silent about the recent rejection from the European Medicines Agency and has vowed to seek a review of the regulatory body’s Committee for Medicinal Products for Human Use (CHMP)’s decision to limit the scope of its Rett syndrome treatment Dayview.
The CHMP’s negative decision on February 26 blows a hole in Acadia’s pivotal Lavender trial, which compared Dayview (trofinetide) to a placebo in 187 women with Rett syndrome, a rare neurodevelopmental disorder.
Now, after considering the CHMP’s refusal, Acadia has vowed to request a reconsideration of the opinion, claiming in a March 2 release that it now has a better understanding of the European regulator’s concerns.
“While we are disappointed with CHMP’s recommendation to deny approval, we remain encouraged by the meaningful benefits trofinetide has shown for people with Rett syndrome,” CEO Katherine Owen Adams said in a statement. “We remain committed to working constructively with EU regulators to explore next steps and bring this treatment to patients.”
In the Acadia study, patients were randomly assigned to receive Dayview or a placebo over a 12-week period and were assessed primarily through caregiver ratings, the Rett Syndrome Behavioral Questionnaire (RSBQ), and the Physician’s Clinical Global Impression-Improved (CGI-I) scale.
The FDA approved approval for Daybue in 2023 based on this study, followed by Canada’s health regulator in 2024 and, more recently, Israel’s Ministry of Health. However, the CHMP took the view that, based on the trials, “the benefits of Dave in the treatment of Rett syndrome are unproven,” and explained it in its refusal using the name of the drug, which would be its commercial name in the EU.
The EMA said the magnitude of the drug’s effect after 12 weeks was “too small” to be expected to be clinically meaningful for patients, and noted that the trial did not assess “some important symptoms of Rett syndrome”. Meanwhile, Acadia’s long-term efficacy data was “complicated” by a “large number” of patients who discontinued the study, the agency said.
Ultimately, 154 of Lavender’s 187 patients elected to proceed to the company’s open-label extension study, while the company’s long-term study, Lilac-2, consisted of 77 patients who had previously completed both trials.
European regulators also determined that the proposed use of Dayview was “not representative of the patients included in the main study, as the main study did not involve patients across different disease stages.”
Acadia had been planning a reexamination since Feb. 2, when CHMP issued a “negative trend vote” to the company during a closed-door meeting regarding the application.
“While the negative trend vote is disappointing and not what we had hoped for, we believe the strong data supporting the approval of trophinetide for the treatment of Rett syndrome in the United States, Canada and Israel speak to the meaningful benefits that trofinetide can offer,” Owen Adams said at the time, noting that more than 1,000 patients across a wide range of ages worldwide are currently being treated. She also pointed to a U.S.-based real-world empirical study that showed results that “closely mirror” the effects observed in Acadia’s clinical trials.
EU law allows drug applicants to request a reconsideration within 15 calendar days of an official opinion, Acadia further explained at the time. The company must then submit the basis for the request within 60 days, after which the CHMP must reconsider its opinion within up to 60 days.
Acadia’s Daybue is the world’s first drug specifically approved to treat Rett syndrome, a complex genetic disorder that occurs in 1 in 10,000 to 15,000 female births worldwide. Acadia estimates that the disease affects approximately 6,000 to 9,000 patients in the United States. In Europe, where the company first applied for approval of Daybue in January 2025, the drug could help about 9,000 to 12,000 patients with the disease, the company said.
In 2025, the company achieved Owen Adams’ goal of annual sales of more than $1 billion for the first time, based on $391 million in sales for Dayview and $692 million in sales for the older Parkinson’s psychosis drug Nuplazid.
The company expects $460 million to $490 million from Daybue this year as it aims to grow its oral solution version of the powder, called Daybue Stix, following FDA approval of the new product in December.
