Final Results from Phase 2 INSTANT Trial of InRhythm™ for the Treatment of Newly Diagnosed and Recurrent Paroxysmal Atrial Fibrillation Presented at 2022 American Heart Association Scientific Sessions
Data Demonstrate Orally Inhaled Flecainide May Provide a Safe, Effective, and Convenient First-Line Treatment Option for Cardioversion of Recent-Onset Newly Diagnosed and Paroxysmal Atrial Fibrillation
Topline Results from the Ongoing Pivotal Phase 3 RESTORE-1 Trial of InRhythm Expected in Early 2024
SAN FRANCISCO, Nov. 07, 2022 (GLOBE NEWSWIRE) — InCarda Therapeutics, Inc. (“InCarda”), a privately-held biopharmaceutical company developing inhaled therapies for cardiovascular diseases, today announced that final data from the company’s Phase 2 INSTANT trial of InRhythm (orally inhaled flecainide) were presented at the 2022 American Heart Association Scientific Sessions. The results were featured in a poster presentation entitled, “Orally Inhaled Flecainide for the Conversion of Recent-Onset, Symptomatic Atrial Fibrillation to Sinus Rhythm: Final Results from the Phase 2 INSTANT Trial,” at the conference, which is being held November 5-7, 2022 in Chicago.
InRhythm is a novel, orally inhaled therapeutic candidate designed to rapidly deliver flecainide, a well-established antiarrhythmic agent, to the heart via the lungs to restore sinus rhythm (SR) in patients with recent-onset newly diagnosed and recurrent paroxysmal atrial fibrillation (PAF) and to relieve their associated symptoms. The therapy is being developed initially for use in a medically supervised setting such as a hospital, emergency room, or physician office and subsequently as a portable treatment that can be self-administered by patients in a non-medically supervised setting (such as the home).
The INSTANT trial was a Phase 2, multicenter, open-label, single-arm study that identified 120 mg as the optimal dose for acute conversion of newly diagnosed AF and recurrent PAF with oral inhaled flecainide and then conducted further safety and efficacy analyses in the target population. In the study, a total of 98 patients received oral inhaled flecainide via an 8-minute nebulization using a breath-actuating nebulizer, followed by 90 minutes of continuous monitoring. Final data demonstrated a conversion rate of approximately 47%, with a median time to conversion of less than 14 minutes from start of inhalation. By Day 5, nearly all patients (97.3%) who converted to SR remained in SR without further treatment. Cardiac adverse events were uncommon and transient, none required treatment, and all resolved without sequelae.
“The results of the INSTANT trial highlight a favorable risk-benefit profile for InRhythm for acute cardioversion of recent-onset AF, suggesting that the therapy may provide a safe, effective, and convenient first-line treatment option for AF conversion,” said Dr. A. John Camm, M.D., professor of clinical cardiology at St. Georges University of London, United Kingdom, and an advisor to InCarda. “These are especially promising findings when one considers the limitations of current treatment options, particularly in the United States. The potential for InRhythm to serve as an effective treatment option that is more rapid, safer and less resource intensive than current therapies is an exciting prospect for both AF patients and the clinicians who treat them.”
InCarda is currently conducting the pivotal Phase 3 RESTORE-1 clinical trial (NCT05039359), a multicenter, randomized, double-blind, placebo-controlled clinical study designed to confirm these Phase 2 efficacy and safety findings in a larger population of patients with recent-onset, symptomatic newly-diagnosed AF or recurrent PAF. The study plans to enroll approximately 400 patients to receive InRhythm (n=300) or a vehicle-matched placebo inhalation solution (n=100). The study’s primary endpoint is the proportion of patients whose AF converts to SR within 90 minutes after initiation of dosing. Safety, as well as several secondary clinical endpoints including AF-related symptoms, hospitalizations, the need for other AF-related interventions, and time to discharge, will also be assessed. Topline study results are expected in early 2024.
“We are pleased to share the final results from the INSTANT study with the scientific community at the 2022 AHA Scientific Sessions. The data presented provided us the rationale for the ongoing pivotal RESTORE-1 study, which is expected to further demonstrate that InRhythm has a therapeutic profile that will meaningfully improve the care of patients with AF,” said Luiz Belardinelli, M.D., chief medical officer at InCarda. “In addition to the benefits offered to patients in terms of rapid restoration of SR and alleviation of symptoms, the RESTORE-1 study is designed to demonstrate that InRhythm will likely reduce healthcare utilization costs by enabling patients to be discharged much more quickly without requiring prolonged hospitalization and by eliminating the need for electrical cardioversion.”
About Atrial Fibrillation (AF)
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia (abnormal heart rhythm) and is characterized by rapid and irregular heartbeats often resulting in palpitations and other symptoms that can be debilitating. A chronic, progressive condition, AF is estimated to affect six million people in the U.S., with that number expected to double by 20501. This expected increase is partially due to the correlation between AF prevalence and an aging population, with approximately 9% of those aged 65 and older affected by the condition1. AF is associated with significant morbidity and a substantial reduction in quality of life, with the condition potentially resulting in exercise intolerance, congestive heart failure, tachycardia-induced cardiomyopathy and stroke. The annual cost of AF to the U.S. healthcare system is estimated at more than $26 billion1.
Paroxysmal AF (PAF) is a type of AF in which episodes occur intermittently and resolve spontaneously in fewer than seven days. Approximately 25% of PAF patients progress to the permanent form of AF within five years2. Common symptoms of PAF can include racing heartbeat, chest pain or pressure, a fluttering feeling in the chest, weakness, fatigue, dizziness, sweating and lightheadedness. Current treatments for patients with PAF rely upon either chronic administration of oral antiarrhythmic drugs or acute hospital-based procedures such as intravenous drug administration and electrical cardioversion, neither of which fully address the unmet need of patients for a rapid-acting treatment that can be administered whenever an episode of PAF occurs. There are currently no approved treatments that can be patient self-administered whenever an episode of PAF occurs.
InRhythm (flecainide for inhalation) is a novel inhaled therapeutic candidate designed to rapidly deliver flecainide, a well-established antiarrhythmic agent, to the heart via the lungs, to restore sinus rhythm (SR) and relieve the patient’s symptoms following the onset of new or recurrent episodes of PAF. InRhythm is intended to address the unmet need for a non-invasive, rapid-acting treatment that can be administered in a medically supervised setting (initial indication) and, ultimately, self-administered by patients anywhere they happen to be, whenever they experience an episode of PAF. Phase 1 clinical results in healthy volunteers demonstrated that InRhythm rapidly and safely delivered flecainide resulting in ECG changes consistent with the potential to restore SR in patients with PAF. The INSTANT Phase 2 trial of InRhythm in patients with recent-onset PAF provided proof-of-concept that oral inhaled flecainide with an administration regimen of eight minutes can safely and rapidly convert recent-onset PAF to normal sinus rhythm. InCarda is currently conducting the pivotal Phase 3 RESTORE-1 trial of InRhythm. With intellectual property protection through 2040, InRhythm represents a first-in-class, potential multi-billion dollar global opportunity to address a significant unmet medical need.
About InCarda Therapeutics
InCarda Therapeutics, Inc. is a privately-held, clinical-stage biopharmaceutical company developing first-of-their-kind inhaled therapies for acute cardiovascular diseases and conditions. The company is leveraging the ability of inhaled therapy to deliver medicine in the “first pass” to cardiac tissue, presenting a small, but effective dose of drug directly to affected regions of the heart. This permits rapid-onset, lower off-target tissue exposure of the drug, lower exposure to cardiac tissue and, more importantly, has the potential to be patient self-administered in a non-medical setting (e.g., home). InCarda employs a de-risked approach by using approved drugs with a long history of efficacy and safety as candidates for the new dosing paradigm via inhalation. The company’s lead development product, InRhythm, is in Phase 3 development to treat acute episodes of PAF, a prevalent atrial arrhythmia. For more information, please visit: www.incardatherapeutics.com.
1 J Am Coll Cardiol. 2014 Dec 2;64(21):2305-7
2 Am Heart J. 2005 Mar; 149(3):489-96
Vida Strategic Partners (media)