CHMP Negative Opinion on Acadia's Rett Syndrome Drug: Implications for Investors and Pharma Teams
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The European Medicines Agency's CHMP has adopted a negative opinion on Acadia Pharmaceuticals' trofinetide (Daybue) for Rett syndrome, citing concerns from the pivotal Lavender trial. This decision impacts Acadia's European market strategy and raises questions for pharma teams developing rare disease therapies.
CHMP’s stance on Acadia’s Rett syndrome drug shifted from refusal to recommendation in four months. After a negative opinion on trofinetide (EU name Daybu) in February 2026, the committee completed re-examination and adopted a positive opinion on 25 June 2026 for neurobehavioural symptoms in patients aged 5 years and older—still pending European Commission authorisation.
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Key Takeaways
- CHMP adopted a negative opinion on the Daybu (trofinetide) MAA for Rett syndrome (patients 2+), citing limited 12-week effect size, incomplete symptom capture, and discontinuation-affected long-term data from LAVENDER.
- Acadia announced it would request re-examination under EU rules (15 days to request; 60 days to file grounds; up to 60 days for CHMP re-review).
- On 25 June 2026 CHMP issued a positive opinion for Daybu 200 mg/ml oral solution for neurobehavioural Rett symptoms in ages 5+ (EMEA/H/C/006482).
- European Commission approval is not automatic; orphan designation maintenance is under separate EMA review.
Why did CHMP first give a negative opinion on Daybu?
Acadia’s Business Wire release said CHMP formally adopted a negative opinion on the Marketing Authorization Application for trofinetide for Rett syndrome in patients two years of age and older. The company said the pivotal LAVENDER trial met co-primary and key secondary endpoints, but CHMP viewed the 12-week treatment effect as limited in magnitude, said the study did not capture all core Rett symptoms, and said longer-term outcome assessment was influenced by discontinuations.
EMA materials describing the refusal explained that the main study enrolled 187 girls and women for 12 weeks with RSBQ and CGI-I endpoints, and that the agency did not consider benefits demonstrated for the proposed broad Rett treatment claim.
Source: Business Wire: Acadia plans re-examination after negative CHMP opinion; ClinicalTrials.gov: LAVENDER NCT04181723.
What did the June 2026 re-examination change?
On 25 June 2026, EMA’s Daybu medicine page states that CHMP, following a re-examination procedure, adopted a positive opinion recommending marketing authorisation for Daybu for treatment of neurobehavioural symptoms of Rett syndrome. The applicant is Acadia Pharmaceuticals (Netherlands) B.V. / Acadia Pharmaceuticals B.V.
The recommended product is a 200 mg/ml oral solution of trofinetide (ATC N07XX24). Benefits are described as primarily based on pivotal study 003, a 12-week placebo-controlled trial with statistically significant co-primary and key secondary improvements; effect sizes were small but judged clinically relevant on the totality of data. Common adverse effects listed include diarrhoea, vomiting, and weight loss.
- Negative CHMP opinion: February 2026 (Acadia re-examination path)
- Positive CHMP opinion after re-examination: 25 June 2026
- Recommended age: 5 years and older (narrower than the refused 2+ claim)
- Pivotal evidence: LAVENDER / study 003 (NCT04181723), n=187
Source: EMA: Daybu (trofinetide) medicine page; Business Wire: DAYBU recommended for EU approval by CHMP.
What should investors and rare-disease teams watch next?
A positive opinion is not a marketing authorisation. Teams should track the European Commission decision, the final SmPC indication language, and whether orphan designation is maintained. The age floor moving to 5+ versus the refused 2+ claim is a material label constraint for EU launch modeling.
In the U.S., trofinetide is already approved as DAYBUE / DAYBUE STIX for ages 2+, so the EU path is a geographic expansion story conditioned on Commission timing—not a first-ever approval globally.
Related coverage: Acadia Parkinson’s campaign, EMA CHMP backs four new medicines, and FDA decisions Q2 2026.
What remains unproven
CHMP’s positive opinion does not guarantee Commission authorisation or national reimbursement. Long-term real-world durability beyond the 12-week pivotal window and the clinical meaning of small effect sizes will remain debated in payer dossiers.
Mechanism of action in Rett syndrome is still described as not fully understood on the EMA overview page.
Related NovaPharma coverage
- EMA CHMP backs four new medicines
- Acadia Pharmaceuticals Parkinson’s campaign
- FDA decisions in Q2 2026
Frequently Asked Questions
Why did CHMP first refuse Acadia’s Daybu for Rett syndrome?
After reviewing the pivotal LAVENDER trial (NCT04181723) in 187 patients, CHMP said 12-week effect sizes were too small to be clinically meaningful, several key Rett symptoms were not assessed, and long-term data were complicated by discontinuations, so benefits were not demonstrated for the proposed use.
What is the current CHMP opinion on Daybu (trofinetide)?
On 25 June 2026, following re-examination, CHMP adopted a positive opinion recommending marketing authorisation for Daybu for neurobehavioural symptoms of Rett syndrome in adults and paediatric patients aged 5 years and older.
Is Daybu approved in the EU yet?
Not yet. A positive CHMP opinion is a recommendation; European Commission marketing authorisation is still required before Daybu can be marketed across the EU.
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