Neuren AGM 30th May, page-23

Excerpt from FDA report: (doesn't mean much to me - interpretation anyone?)

1.2. Conclusions on the Substantial Evidence of Effectiveness The placebo-controlled study ACP-2566-003 was an adequate and well-controlled study that supports approval of trofinetide for the treatment of children and adults with Rett syndrome. ACP-2566-003 was a multicenter study that provided reliable and statistically significant evidence that treatment with trofinetide for 3 months demonstrated benefit on the co-primary endpoints of the Rett Syndrome Behavior Questionnaire (RSBQ) and clinician rating of the Clinician Global Impression of Improvement (CGI-I). The study also demonstrated a statistically significant difference favoring trofinetide on the prespecified secondary endpoint of the Communication and Symbolic Behavior Scales Developmental Profile – Infant and Toddler – Social Composite Score (CSBS-DP-IT-SCS). This scale, developed as a screening tool to alert clinicians to potential communication deficits in infants and toddlers, is not fit for purpose for determining a treatment-related benefit in the complex concept of social reciprocity and communication ; however, the finding of a benefit on this endpoint in trofinetide Reference ID: 5139595 (b) (4) Clinical Review Michael A. Dimyan, MD NDA 217026 DAYBUE (Trofinetide) CDER Clinical Review Template 14 Version date: March 8, 2019, for all NDAs and BLAs patients is still supportive of overall effectiveness. Further confirmatory evidence of effectiveness was obtained in study NEU-2566-RETT-002, a multisite Phase 2 single-blind placebo run-in, randomized double-blind, placebo-controlled dose ranging clinical trial. The objective of NEU-2566-RETT-002 was to investigate the safety, tolerability, and pharmacokinetics of treatment with 3 different doses of oral trofinetide in girls ages 5 to 15 with Rett syndrome. A total of 82 subjects were enrolled and five outcome measures explored, but the primary support for effectiveness came from comparison of RSBQ and CGI-I in 24 placebo-treated subjects and 27 subjects receiving 200 mg/kg twice daily of trofinetide. Although formal statistical testing for efficacy was not prespecified, the least square means difference between trofinetide and placebo in RSBQ met nominal significance (p=0.042) as did CGI-I (P=0.029).