CHMP negative opinion for Daybue (trofinetide) in the treatment of Rett syndrome – Acadia Pharmaceuticals

The EMA has recommended the refusal of the marketing authorisation for Daybue, intended for the treatment of Rett syndrome, a rare inherited condition that affects the brain and nervous system. Acadia Pharmaceuticals presented the results from a main study in 187 girls and women with Rett syndrome who received either Daybu(e) or placebo (a dummy treatment) every day for 12 weeks. The main measures of effectiveness were changes in patients’ scores on two standard scales: the Rett Syndrome Behaviour Questionnaire (RSBQ) scale, which measures patients’ behavioural, emotional and physical symptoms, and the Clinical Global Impression of Improvement (CGI-I) scale, which measures patients’ overall health improvement as observed by their clinician.

The EMA considered that the size of Daybu’s effects observed after 12 weeks of treatment are too small and are therefore not expected to be clinically meaningful for patients. The Agency also noted that the study did not assess several key symptoms of Rett syndrome and that the conclusion on the long-term effectiveness data was complicated by the large number of patients who withdrew from the study.

The Agency also considered that the proposed use for Daybu — treatment of Rett syndrome — was not representative of the patients included in the main study, as the latter did not involve patients across the different disease stages. Therefore, the Agency’s opinion was that the benefits of Daybu in the treatment of Rett syndrome have not been demonstrated and it recommended refusing marketing authorisation. Acadia Pharmaceuticals, may ask for re-examination of the opinion within 15 days of receiving the opinion.