Data Demonstrate Achievement of Rapid Conversions from Atrial Fibrillation to Normal Sinus Rhythm
Study Findings Provide Proof of Concept for First-of-its-Kind Inhaled Antiarrhythmic for Treatment of Paroxysmal Atrial Fibrillation (PAF)
Provides Roadmap for Start of Pivotal Phase 3 in Medically Supervised Setting in 2021
San Francisco, CA – November 13, 2020 – InCarda Therapeutics, Inc. (“InCarda”), a privately-held biopharmaceutical company developing first-of-their-kind inhaled therapies for cardiovascular diseases today announced the presentation of positive data from the open-label, dose-escalation Part A portion of the company’s multinational INSTANT Phase 2 clinical trial of InRhythm™ (flecainide for inhalation) in patients with recent-onset paroxysmal atrial fibrillation (PAF) at the American Heart Association’s (AHA) Scientific Sessions 2020. The positive study results reported today during the AHA conference provide the first proof of concept for inhaled flecainide as a potentially safe and effective therapeutic option for rapidly converting PAF to normal sinus rhythm (NSR).
InRhythm is a novel inhaled therapeutic candidate designed to rapidly deliver flecainide, a well-established antiarrhythmic agent, to the heart via the lungs to restore NSR and to relieve symptoms associated with acute episodes of PAF. The therapy is being developed initially for its use under medical supervision in 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) to rapidly achieve conversion of PAF to NSR.
Dr. Harry J.G.M. Crijns, professor, chair of cardiology and board member of the Cardiovascular Research Institute Maastricht (CARIM) at Maastricht UMC+, and co-principal investigator of the INSTANT trial, presented data from Part A of the INSTANT trial. The results demonstrated the rapid achievement of therapeutic plasma levels (Cmax > 200 ng/mL) of flecainide via oral inhalation with InRhythm. Approximately 80% of patients who received the study’s highest administered dose (120 mg) achieved a flecainide Cmax > 200 ng/mL. For all study participants who reached these therapeutic plasma levels, nearly 50 percent achieved a successful conversion from PAF to NSR. Importantly, those successful conversions occurred rapidly, with a median time to conversion of 3.6 minutes after the end of the administration of InRhythm (total inhalation time for InRhythm administration is eight minutes). The treatment was shown to be safe and well-tolerated, and the majority of adverse events were transient, mild in severity and resolved without treatment.
“There is growing clinical and scientific evidence to support the importance of rhythm control in the overall management of atrial fibrillation,” said Jeremy N. Ruskin, M.D., professor of medicine at Harvard Medical School and founder and director emeritus of the Cardiac Arrhythmia Service at Massachusetts General Hospital and co-principal investigator of the INSTANT study. “Currently available treatment options for the acute conversion of atrial fibrillation to normal sinus rhythm are limited and do not fully address the unmet needs of improving patients’ symptoms and quality of life and reducing healthcare costs. This novel therapy for rapid restoration of normal rhythm, if successful in pivotal clinical trials, has the potential to play a significant role in addressing these unmet clinical needs.”
Based on these positive study results, InCarda has commenced enrollment of Part B of the INSTANT study which includes a confirmatory cohort using the selected optimal therapeutic dose (120 mg) and a pilot study referred to as the “Patient-led Sub-study.” In this latter study patients who have already experienced a safe cardioversion with InRhythm will receive training so that they can self-administer InRhythm under medical supervision when another (“recurrent”) episode of PAF occurs. In addition to current study sites in the Netherlands and Belgium, InCarda will start recruiting patients in the US later this year.
“The data presented today from the INSTANT study provide the first proof of concept of this novel strategy to deliver flecainide via oral inhalation to rapidly restore NSR in patients with symptomatic episodes of recent-onset PAF. These data will be used to finalize the design of a multinational, Phase 3 trial of InRhythm to support marketing approval for in-hospital, medically supervised use. We expect to initiate this study in the first half of 2021,” said Luiz Belardinelli, M.D., chief medical officer of InCarda.
“With six million atrial fibrillation patients in the US contributing to over $26B in annual healthcare expenditures, and more than 30 million atrial fibrillation patients worldwide, there is a tremendous opportunity for InCarda to uniquely address this important and growing need,” said Grace E. Colon, Ph.D., chief executive officer of InCarda. “We look forward to the next steps in the development of this important new therapy and reporting on several key company milestones over the next year.”
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 normal sinus rhythm (NSR) and relieve the patient’s symptoms following the onset of an episode 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 NSR in patients with PAF. InCarda is currently conducting the INSTANT Phase 2 trial of InRhythm in patients with recent-onset PAF. InRhythm represents a first-in-class, 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 2 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