Single Pivotal Phase 3 Trial to Support Filing of New Drug Application
Positive Phase 2 Efficacy and Safety Data for InRhythm Recently Highlighted as “Editor’s Pick” in Circulation: Arrhythmia and Electrophysiology
SAN FRANCISCO, CA – July 26, 2022 – InCarda Therapeutics, Inc. (“InCarda”), a privately-held biopharmaceutical company developing inhaled therapies for cardiovascular diseases, today announced enrollment of the first patient in the company’s pivotal Phase 3 RESTORE-1 clinical trial of InRhythm™ (orally inhaled flecainide) in patients with newly-diagnosed atrial fibrillation (AF) or recurrent paroxysmal atrial fibrillation (PAF). At an End-of-Phase 2 (EOP2) meeting with the U.S. Food and Drug Administration (FDA), InCarda received FDA concurrence that this single Phase 3 trial would be acceptable to support the filing of a New Drug Application (NDA) for InRhythm for the acute conversion of recent-onset AF to sinus rhythm (SR) under medical supervision.
RESTORE-1 is a Phase 3, multicenter, randomized, double-blind, placebo-controlled clinical study designed to evaluate the efficacy and safety of InRhythm compared with placebo in 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 (e.g., 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 late 2023.
“The initiation of this groundbreaking pivotal Phase 3 trial represents an important milestone for both InCarda and the large and underserved AF patient community, demonstrating InCarda’s success leveraging our significant combined expertise in cardiovascular disease and inhalation technology. We believe that InRhythm has the therapeutic profile to substantially move the needle for AF patients, potentially offering them a first-of-its-kind inhaled treatment that can safely and rapidly convert recent-onset AF episodes to sinus rhythm. We look forward to confirming the best-in-class efficacy and safety results from our Phase 2 program,” said Grace Colón, Ph.D., president and chief executive officer of InCarda.
InRhythm is a novel, orally inhaled therapeutic designed to rapidly deliver flecainide, a well-established antiarrhythmic agent, to the heart via the lungs to restore SR and relieve AF-related symptoms in patients with recent-onset, newly diagnosed or recurrent PAF. The therapy is initially being developed for use in a medically supervised setting such as a hospital or emergency room and then, in the future, as a portable treatment that can be self-administered by patients. InCarda successfully completed a Phase 2 study for InRhythm under medical supervision demonstrating that therapy can safely and rapidly convert recent onset AF to SR, with a median time to conversion of less than 15 minutes after initiation of inhalation treatment.
“We are excited to have enrolled the first patient in the RESTORE-1 study, as we believe that orally inhaled flecainide has the tremendous potential to offer AF patients a much more rapid and non-invasive treatment for restoring normal sinus rhythm,” said Mark Y. Lee, MD, FACC, RESTORE-1 study investigator at MemorialCare Long Beach Medical Center. “Current acute treatments of AF episodes in the hospital consist of IV rhythm control medications with poor risk-benefit, IV rate control medications that can reduce symptoms but don’t directly treat the AF, or electrical shock that is highly resource intensive and potentially traumatizing for patients. We have seen significant patient interest in participating in the RESTORE-1 study, which underscores the demand for better acute treatments for AF conversion.”
InCarda’s Chief Medical Officer, Dr. Luiz Belardinelli, further stated, “Advancing the development of InRhythm into this pivotal Phase 3 study represents a major step towards demonstrating that episodes of recent onset AF can be safely and rapidly terminated via pulmonary delivery of anti-arrhythmic drugs such as flecainide. The results of the Phase 2 INSTANT study give us confidence that the Phase 3 trial will demonstrate a favorable benefit-risk profile for InRhythm. In addition to rapid conversion and symptom relief, we plan to demonstrate a reduction in the time and expense required to treat patients with AF in-hospital, including rapid hospital discharge and the avoidance of electrical cardioversion and hospitalization. We are very appreciative for the support and dedication of our clinical trial investigators and advisors, and give thanks to the many healthy volunteers and patients with AF who have participated in our trials to date.”
Results from InCarda’s Phase 2 INSTANT study were recently published in an “Editor’s Pick” manuscript in the peer-reviewed publication Circulation: Arrythmia and Electrophysiology. The published data from the INSTANT study showed that for the first time, a single dose of inhaled flecainide can rapidly convert recent-onset (≤ 48 hours), symptomatic episodes of newly diagnosed AF or recurrent PAF to SR. Cardiac adverse events were uncommon, none required treatment, and all resolved without sequelae. This dose-ranging study also identified the optimal dose of InRhythm (120 mg), which InCarda is studying in the pivotal Phase 3 RESTORE-1 study. The manuscript may be accessed at https://www.ahajournals.org/doi/10.1161/CIRCEP.121.010204.
Additionally, the company presented results from the Phase 2 INSTANT study in a poster presentation at the Heart Rhythm Society’s Heart Rhythm 2022 conference The presentation, entitled, “Orally Inhaled Flecainide for the Conversion of Recent-onset, Symptomatic Atrial Fibrillation to Sinus Rhythm: Results from the INSTANT Phase 2 Study,” can be accessed via InCarda’s website by visiting https://incardatherapeutics.com/2022/05/02/incarda-presents-phase-2-safety-and-efficacy-data-for-inrhythm-orally-inhaled-flecainide-at-the-2022-heart-rhythm-society-conference-in-san-francisco.
Additional Phase 2 data from INSTANT will be presented in two moderated poster presentations at the upcoming European Society of Cardiology conference. Both presentations will take place on August 29th in Barcelona, Spain.
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