Budiodarone is an oral anti-arrhythmic agent in Phase 2b clinical development for the treatment of patients with atrial fibrillation. Budiodarone was designed to have the efficacy of amiodarone, a drug that has been used for many years, despite its adverse side effects, because physicians consider it to be the most effective drug for treating patients with atrial fibrillation. Amiodarone accumulates in many different organs and can only be metabolized by CYP450, potentially leading to serious side effects that are not immediately reversible upon withdrawal of the drug. Since budiodarone is predominantly metabolized through the esterase pathway, accumulation in the organs and drug-drug interactions are expected to be reduced.
Budiodarone's affinity for the major calcium, potassium and sodium ion channels, as well as certain receptors in the heart, very closely matches that of amiodarone. Budiodarone, like amiodarone, contains iodine which we intentionally retained since we believe it contributes to amiodarone's efficacy. A variety of preclinical studies with budiodarone provide evidence that the drug preserves the efficacy of amiodarone but with more rapid metabolism and no tendency towards accumulation.
Atrial Fibrillation
Atrial fibrillation is the most common form of cardiac arrhythmia, or abnormal heart rhythm, affecting greater than 6.4 million people in the United States, Europe and Japan. It is estimated that atrial fibrillation is responsible for more than 75,000 strokes per year in the United States alone. Atrial fibrillation is caused when the atria quiver instead of beat. During atrial fibrillation, the atria contract and relax erratically between 350 and 600 times per minute versus normal heart rhythm of 60 to 80 beats per minute. Patients with atrial fibrillation experience debilitating symptoms and suffer a compromised quality of life. Because the pumping function of the atria does not work properly in atrial fibrillation patients, blood is not completely emptied from the heart's chambers, causing it to pool and sometimes clot. In patients with atrial fibrillation, clotted blood can dislodge from the atria and flow to the brain, causing stroke. Atrial fibrillation also compromises the pumping function of the heart often leading often to intolerable symptoms that need therapy.
Atrial fibrillation treatments focus on a reduction of symptoms and returning the heart to normal rhythm. Concerns surrounding available atrial fibrillation treatments include both safety and efficacy issues. The most common treatment for atrial fibrillation is drug therapy. Current pharmacological treatments for atrial fibrillation are limited in their use due to safety and efficacy issues, while non-pharmacological approaches such as implantable devices and surgery are currently less favored because of their costs and invasive nature.
Budiodarone Development Status
We have completed one pilot Phase 2 clinical trial in patients who suffer from repeated episodes of atrial fibrillation, or paroxysmal atrial fibrillation, along with a later Phase 2b clinical trial in the same type of atrial fibrillation patient. This is a patient population that is particularly difficult to treat. In the pilot study, budiodarone quickly reduced the amount of time these patients were in atrial fibrillation by up to 87%.
The Phase 2b study, based upon the design of the pilot study, has recently been completed in patients with similar atrial fibrillation. The results were essentially the same in both studies. In this Phase 2b study, atrial fibrillation burden (or the percent of time patients spend in atrial fibrillation) was significantly reduced in two dose groups tested. The reduction in burden was up to 83% as compared to baseline in the third month of treatment at the 600 mg BID dose, and the overall dose response effect across all three doses tested was both robust and linear with a p=0.0001. Based upon these results, we believe we have sufficient data to seek a large pharmaceutical company partner to continue to develop the product candidate through Phase 3 clinical trials and commercialization. We anticipate that the partner will be responsible for these late-stage development and commercialization costs.
Clinical Trial Information
Would you like to learn about budiodarone in clinical trials? Details on the current trials, and contact information for questions you may have, can be found at ClinicalTrials.gov. There are currently no clinical trials underway testing budiodarone. Please continue to check back for details on future clinical trials.
The ClinicalTrials.gov website is maintained as a public service by the United States National Institutes of Health and contains information provided by us.
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