According to InCarda, data from the Phase 3 RESTORE-1 trial of FlecIH-103 flecainide inhalation solution for aroxysmal atrial fibrillation (PAF), which was initiated in July 2022, support continued development despite the early termination of the study due to disappointing efficacy and plasma concentrations. InCarda cites delivery problems with the jet nebulizer used in the study as a reason for the disappointing results. The company says that it has confidence in improved delivery as it moves forward with an Aerogen vibrating mesh nebulizer and expects to re-initiate studies in PAF patients next year.
The company reports that the Phase 3 trial enrolled 54 patients out of an expected 400 before the trial was stopped. Termination occurred after the rate of cardioversion from PAF to sinus rhythm was only 31%, compared to 47% in an earlier Phase 2 study “and unexpected drug-device incompatibility not previously observed in the Phase 2 clinical trial.” InCarda notes that the 31% cardioversion rate was statistically significant compared to placebo and emphasizes that no safety concerns were noted.
Interim data from a Phase 1 bridging study is encouraging, InCarda said, demonstrating that it can achieve the same Cmax using the Aerogen nebulizer as the Cmax achieved using the jet nebulizer in the Phase 2 trial but with only a third of the amount of flecainide. No new safety concerns were identified.
InCarda Chief Medical Officer Luiz Belardinelli commented, “We believe that inhaled flecainide has the potential to be a valuable treatment for patients with recent-onset episodes of PAF. While RESTORE-1 did not achieve the level of efficacy desired and the trial was terminated early, the analysis showed a statistically significant higher conversion rate in the active arm compared to the placebo for the 54 patients evaluated, and the continued encouraging safety and tolerability profile of FlecIH-103 suggest that this treatment could become an important option for patients with acute episodes of recent-onset of PAF. The trial also indicated that patients whose PAF converted to NSR had their symptoms relieved, required fewer interventions, and were discharged earlier from the ER, thus suggesting attractive pharmacoeconomic benefits of orally inhaled flecainide.”
CEO Carlos Schuler said, “I am very excited by the ability of the new drug-delivery platform to deliver flecainide reliably. Given the positive Phase 1 results to date, I am optimistic that we will be able to achieve commercially attractive efficacy and safety and demonstrate pharmacoeconomic benefits in the registrational studies currently being planned.”
Read the InCarda Therapeutics press release.
