Long-Term Trofinetide Treatment Persistence and Dosing Patterns in Rett Syndrome: A Post Hoc Analysis of Linked Trial and Real-World Specialty Pharmacy Data

Trofinetide (TRO) approval by the US FDA enabled participants from the placebo-controlled (LAVENDER) and open-label extension (LILAC-1 and LILAC-2) trials to continue TRO commercially. We assessed participant characteristics, adverse events (AEs), dosing patterns, and time on TRO among LILAC-2 participants who continued or did not continue TRO post-approval. This retrospective post hoc analysis used participant-level data from the LAVENDER, LILAC-1, and LILAC-2 trials linked with specialty-pharmacy data to categorize TRO continuers and non-continuers by post-launch prescription (RX) shipment status. Demographics (e.g., age, race) were evaluated at baseline (LAVENDER). Outcomes included Rett Syndrome Behavior Questionnaire (RSBQ) total and domain scores, Clinical Global Impression-Improvement (CGI-I) score from baseline through LILAC-2, highest recorded AE severity for each AE during LILAC-2, and dosing patterns (mean twice-daily dose by volume [ml], weight [mg/kg]; percent target daily dose [%TDD]) pre- and post-launch. Post-launch treatment persistence (allowable RX shipment gap ≤ 90 days) and time on TRO were also assessed. Among 77 LILAC-2 participants alive and eligible ( n = 73) to shift to real-world usual care, 57/73 (78.1%) were classified as TRO continuers; the rest were non-continuers. Baseline mean age was 10.5 vs 11.9 years; most were white (89.5% vs 100.0%). Both groups achieved clinically meaningful total RSBQ improvement from baseline to LILAC-2 week 52 (8.2 and 6.2 points), with improvements also observed across RSBQ domains and CGI-I. AEs were predominantly mild to moderate, especially among continuers. TRO continuers showed gradual dose reduction during trials with stabilization post-launch (~ 40 ml), while TRO non-continuers showed fluctuations throughout; post-launch %TDD showed minimal change of ~ 92.7% (month 1) and ~ 91.0% (month 12) among TRO continuers. Average time on TRO among continuers was 4.3 years from baseline through available real-world follow-up. Approximately 75% of LILAC-2 participants continued TRO post-approval; all persisted for ≥ 12 months post-launch and exhibited stable dosing patterns. Both groups demonstrated clinically meaningful RSBQ improvements through week 52 of LILAC-2 and predominantly mild-to-moderate AEs during LILAC-2.