InCarda Therapeutics Reveals RESTORE-1 Phase 3 Trial Results and Future Development Plans

InCarda Therapeutics, Inc., a biopharmaceutical company based in San Francisco, has announced significant advancements in the development of its inhaled flecainide acetate solution, FlecIH-103, aimed at treating paroxysmal atrial fibrillation (PAF). The progress follows a detailed analysis of the RESTORE-1 Phase 3 clinical trial, which, despite its early termination, provided promising data supporting the inhaled treatment's efficacy and safety.

The RESTORE-1 trial was designed to evaluate the efficacy and safety of FlecIH-103 when administered via a jet nebulizer. This Phase 3 trial aimed to enroll 400 patients but was halted prematurely after 54 patients had been enrolled. This early termination was due to lower-than-anticipated efficacy and plasma flecainide levels, not due to safety concerns. Despite these challenges, the trial demonstrated a statistically significant cardioversion rate of 31% in the treatment group compared to the placebo group.

The trial results were presented at the 2024 European Society of Cardiology meeting in London. They highlighted the rapid restoration of normal sinus rhythm (NSR) in patients with PAF, with a median time of approximately 13 minutes from the start of dosing. Additionally, early restoration of NSR led to significant pharmacoeconomic benefits. Notably, 80% of patients whose atrial fibrillation (AF) converted to sinus rhythm were eligible for discharge from the hospital within two hours, compared to 30% of those whose PAF did not convert. Moreover, 83% of patients who converted to NSR within 90 minutes were symptom-free, versus 28% in the non-conversion group.

The trial's early termination prompted InCarda to transition to a novel drug-delivery platform developed by Aerogen Ltd., which offers a more efficient and reliable delivery method. This new platform utilizes a vibrating mesh aerosol generation engine and a breath-synchronized dosing system, enhancing flecainide delivery to the heart through the lungs.

Preliminary interim results from a Phase 1 clinical study conducted in Australia using this new delivery system have been promising. The study showed that peak plasma flecainide concentrations were similar to those achieved in the Phase 2 INSTANT trial, with only one-third of the drug amount needed compared to the previous nebulizer method. Additionally, electrocardiographic changes observed were transient and within safe ranges.

InCarda plans to complete the ongoing Phase 1 study and explore additional dosing regimens, including booster doses. The company aims to initiate new safety and efficacy trials in 2025, focusing on both medically supervised settings and portable self-administration.

Dr. Luiz Belardinelli, Chief Medical Officer of InCarda, expressed optimism about the potential of inhaled flecainide as a valuable treatment for patients with recent-onset PAF. He noted that despite the early termination of RESTORE-1, the trial demonstrated a statistically significant higher conversion rate in the active treatment group, along with encouraging safety and tolerability profiles.

InCarda's co-founder and CEO, Carlos Schuler, Ph.D., also voiced excitement about the new drug-delivery platform's capabilities. He highlighted the positive Phase 1 results and expressed confidence in achieving commercially viable efficacy and safety in upcoming registrational studies.

PAF is a type of atrial fibrillation characterized by intermittent episodes that resolve spontaneously. It can cause symptoms like rapid heartbeat, chest pain, and dizziness. Current treatments include chronic oral antiarrhythmic drugs or acute hospital-based procedures, none of which offer a rapid-acting, self-administered solution for patients. Inhaled flecainide aims to fill this gap, providing a quick and effective treatment option for acute PAF episodes.

InCarda continues to advance the development of inhaled flecainide, leveraging intellectual property protection potentially extendable through 2045. The company remains committed to addressing the significant unmet medical need for rapid, self-administered treatment options for PAF.

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