Alyssa Peckham,1 Amitha Ananth,2 Loan Robinson,1 Claire Zhu,1 Ratna Revankar,1 Louise Cosand1
1 Acadia Pharmaceuticals Inc., San Diego, CA
2 University of Alabama at Birmingham, Birmingham, AL
Objective: To estimate the time to response (TTR) to trofinetide in patients with Rett syndrome (RTT) who participated in the trofinetide clinical trials.
Background: Trofinetide is approved for the treatment of RTT in patients aged ≥2 years in the US, and patients aged ≥2 years weighing ≥9 kg in Canada. Anecdotal, real-world reports from RTT experts at US centers of excellence suggest that some patients require more than 12 weeks to respond to trofinetide.
Design/Methods: Participants who received trofinetide for 52 weeks were included. Participants
randomized to trofinetide in LAVENDER were included if they had a Clinical Global Impression-
Improvement (CGI-I) score at week 12 in LAVENDER (month 3) and week 40 in LILAC (month 12). Participants randomized to placebo in LAVENDER were included if they had a CGI-I score at week 12 in LILAC (month 3) and week 12 in LILAC-2 (month 12). For some participants, the CGI-I score at month 6 (ie, weeks 12 and 26 in LILAC for the trofinetide and placebo groups, respectively) was analyzed. TTR periods included 0-3 months, 3-6 months, and 6-12 months. Results were pooled across treatment arms.
Results: Overall, 80 participants met analysis criteria. By month 12, 58 (72.5%) participants
improved, 21 (26.3%) neither improved/worsened, and 1 (1.3%) worsened. Of those improved, there were 33 (56.9%) participants with an estimated TTR within 0-3 months, 12 (20.7%) within 3-6 months, and 12 (20.7%) within 6-12 months. There was 1 (1.7%) participant who improved after month 3 and by month 12, but TTR estimation was not possible due to missing month 6 value.
Conclusions: Trofinetide should be administered for at least 6 months, and potentially up to 12
months, to allow for adequate TTR.
