Budiodarone is a clinical-stage oral drug candidate that is being investigated for its potential to treat refractory atrial fibrillation (AF), defined as those patients refractory to other anti-arrhythmic drugs or catheter ablation. Budiodarone is also being studied to suppress ventricular arrhythmias and device firing in patients with implantable cardioverter defibrillators (ICDs).
Results from two Phase 2 clinical trials in AF and pre-clinical data suggest that budiodarone may potentially offer dose-dependent reduction of atrial fibrillation burden (AF burden), suppression of symptoms and AF recurrence. As part of the budiodarone clinical development program, we intend to demonstrate budiodarone’s potentially enhanced safety profile compared to the gold standard amiodarone, based on budiodarone’s lower risk of long term tissue accumulation and related organ toxicities. Budiodarone has a more rapid onset of action compared to amiodarone. Experience with budiodarone in initial clinical trials demonstrates that, unlike amiodarone, budiodarone can be easily dose adjusted to optimize effect.
In late 2016, the budiodarone U.S. patent portfolio was expanded with claims directed to two new indications for clinical development, significantly extending the product IP protection for minimally 15-20 years in the U.S. These two indications include 1) the use of budiodarone in treating patients with refractory AF who have failed other first line therapies and 2) the use of budiodarone in combination with novel oral anticoagulants (NOACs) in such patients.
The combination of budiodarone, an anti-arrhythmic drug candidate with a potentially favorable risk-benefit profile, with an effective anticoagulant (NOAC) might have the clinical potential to be used both short term to produce effective and safe pharmacological cardioversion of AF and long term to maintain sinus rhythm and maximize the reduction in stroke risk.
Budiodarone is still under development and has not been shown to be safe and effective and has not been approved by any regulatory agency.
In our Phase 2 clinical trials to date,1,2 budiodarone has shown a significant reduction in AF burden in a dose-related fashion. AF episodes of long duration are currently understood to correlate with increased risk of stroke. High AF burden is associated with increased risk of hospitalization in AF patients. Budiodarone is in development to treat episodes of atrial fibrillation, improve symptoms and recurrence in patients who are refractory to other anti-arrhythmic drugs or catheter-based ablation.
Implantable cardioverter defibrillators (ICDs) prolong life by treating ventricular arrhythmias when they occur. Many patients with ICDs have disabling symptoms due to sustained arrhythmias which may also lead to painful shocks from the device. These sustained life-threatening ventricular arrhythmias can be suppressed with an effective oral anti-arrhythmic drug. About two million people worldwide have an ICD, and up to 50% of these patients require additional treatment with an anti-arrhythmic agent to reduce arrhythmias and ICD firing.3,4 Existing therapies are limited in their efficacy, and some of the drugs have high rates of toxicity over time. Armetheon is investigating budiodarone for the prevention of life threatening ventricular arrhythmias and device firing in patients with ICDs. If developed for this indication, budiodarone could become the first anti-arrhythmic agent specifically approved for this patient population.
When arrhythmias in an ICD recipient result in disabling symptoms or a device firing, efforts to prevent future arrhythmia episodes may include ablative therapy or drug therapy. Ablation is of limited success, often temporary, and is almost always augmented with drug therapy. There are currently no approved anti-arrhythmic drugs for management of ventricular tachycardia (VT) in ICD patients.