Authors :
Presenting Author: Stan Skafidas, Professor – University of Melbourne
Pat Kelly, CEO, MSEE – Remagine Labs
Steven Duvall, PhD – Remagine Labs
Heather Benson, PhD – Remagine Labs
Zhang Qian, PhD – Remagine Labs
HaoZhe Yoh, PhD – University of Melbourne
Yang Yu, PhD – University of Melbourne
Tian Li, PhD – University of Melbourne
Annika Ahrens, BPharmSc (Hons) – Remagine Labs
Rationale: Fenfluramine is approved for treating Dravet syndrome and Lennox-Gastaut syndrome, but its oral liquid formulation presents clinical challenges: adherence issues, plasma concentration variability, and imprecise dosing, especially in pediatric populations. A programmable, electronically controlled transdermal patch could address these limitations by offering smoother pharmacokinetics, reduced caregiver burden, and improved patient outcomes.
Methods: We developed a wearable iontophoretic patch for fenfluramine hydrochloride (FFA·HCl), designed for pediatric-friendly, long-term transdermal delivery. In vitro permeation was assessed using porcine skin mounted in custom Franz diffusion cells (n=3), with a PVA-based hydrogel containing FFA·HCl under 0.125 mA/cm² current. Passive (no current) controls were included. Flux and lag time were derived from regression analysis of the cumulative permeation curve. Simulated plasma concentrations were modeled using a two-compartment pharmacokinetic model derived from published FINTEPLA® submission data for a 70 kg adult, informed by in vitro flux values and published therapeutic ranges. A placebo wear test using NaCl-loaded patches was conducted in a healthy adult volunteer to evaluate wearability and local effects over 8 hours.
Results:
Iontophoretic delivery achieved 39.4-fold higher steady-state flux (70.2 ± 7.4 µg/cm²/h) compared to passive controls, with half the lag time (1.15 h vs 2.52 h). Extrapolated to a 15 cm² patch, cumulative delivery over 24 h was consistent with the 26 mg/day oral-equivalent dose. Simulated plasma profiles demonstrated that patch-based delivery can achieve and maintain plasma concentrations within the clinical therapeutic range (mean 43.87 ± 28.61 ng/mL, per Schoonjans et al., Epilepsia 2022), with smoother profiles and less fluctuation than oral dosing. Additional simulated scenarios illustrated programmability benefits, including gear-shift style rapid ramps, steady-state modulation via current control, and multi-day titration mimicking clinical response patterns. No irritation or discomfort was observed in the 8-hour placebo wear test. Longer-duration wear and human skin sensitivity studies are planned.
Conclusions:
A programmable iontophoretic patch can safely deliver therapeutic doses of fenfluramine with controlled and consistent pharmacokinetics. This platform offers a non-oral alternative aligned with the needs of pediatric epilepsy patients and enables clinician-led personalization. These results support advancement toward formulation optimization, safety studies, and first-in-human trials in 2026.
Funding:
Supported by the Australian Government through a Cooperative Research Centres Projects (CRC-P) grant.