Delivering Drugs Straight to the Heart – InCarda’s Acute Atrial Arrhythmia Treatment

Narsi Rangachari, co-founder of InCarda Therapeutics talked about InCarda’s novel approach to delivering drugs straight to the heart.

Scheme of atrial fibrillation (top) and sinus rhythm (bottom). The purple arrow indicates a P wave, which is lost in atrial fibrillation. (Photo credit: Wikipedia)

Approximately 20 million patients a year in the US, experience one or more forms of acute cardiac conditions. Current therapies to treat acute conditions are not optimal. They are slow, have not effective presenting higher risk. Current therapies also seem to cause a great deal of patient discomfort, resulting sometimes in poor quality of life, frequent and continuing ER visits, and extended hospital stay. Cardiac conditions add a tremendous burden to the overall healthcare costs. Cardiac arrhythmias rank as number 7 among the top 10 reasons for hospitalizations. There are little to no acute interventions in treating patients with atrial arrhythmias.

Atrial Fibrillation (also called Afib or AF) is a serious but non-life threatening condition that causes irregular and often-rapid heartbeats and many a time where the patient experiences debilitating symptoms. Global prevalence of AF is over 34 million and growing, with more than 5 million Americans estimated to suffering from the disease. Oral tablets approved for chronic treatment of AF are 30-50% effective, have very slow onset and are generally not suited for acute intervention. Few of the new drugs have made it to the market and these have not proven to be safe and effective. Ablation is an expensive and invasive procedure requiring repeat procedures, require hospital stays and are often associated with serious adverse events.

InCarda’s patented technology focuses on targeting the drugs to the heart via the lungs, said Rangachari. He spoke about a variety of technologies available to deliver drugs to and through the lungs. These included portable nebulizers, dry powder aerosols and breath controlled pulmonary delivery. The benefit of inhalation in treating atrial arrhythmias is that it delivers a “first pass” to cardiac tissue, delivering a bolus of drug directly to regions of the heart where stimuli for acute atrial arrhythmias arise. This permits rapid onset, lower off-target tissue exposure of the drug and – importantly – can be self-administered by the patient. InRhythm currently under development to treat widespread symptomatic atrial arrhythmia conditions like paroxysmal atrial fibrillation (PAF) uses approved drugs in a new dosing paradigm. InCarda has developed a de-risked approach by employing well studied, first line drugs, with long histories of efficacy and safety. In addition, the Company is using validated endpoints with established clinical assays and using commercially available inhalation devices for clinical evaluation. It was a very interesting talk and was followed by Q&A.

PS – See similar article on Pearl Therapeutics http://bit.ly/NnPhwI , a tiny company that focused on inhalation drug delivery for conditions like asthma and COPD and was bought by Astra Zeneca for $1.15 Billion.

Ambulatory ECG Monitoring

David Bondietti, VP of Marketing and Business Development at BioMedical Systems, talked about ambulatory ECG monitoring systems, at www.bio2devicegroup.org event.  There are four broad categories of devices that can record an ambulatory electrocardiogram or the electrical activity of the heart, while an individual is doing usual activities.  Sometimes heart problems become noticeable during certain activities like exercise, eating or even sleeping and continuous monitoring can detect abnormal heartbeats.

Holter monitoring devices were among the first ambulatory devices and they can now record every beat for up to 24 to 72 hours and give very detailed reports, recording up to 100,000 heartbeats in 24 hours..  All ECG data is analyzed via holter analysis software, all findings are validated by 4 certified cardiac technicians and these devices remain the gold standard in cardiac care.  These devices require very little patient compliance and they record all data, not just sporadic data.  However, short recording duration is a major limitation and additional limitation is that it takes some time to get the results.  Continuous recorder can be implanted under the skin for up to a year of recording but iRhythm has latest holter technology.  It’s zio patch goes over a patient’s chest and allows up to 14 days of continuous ECG recording.  It can then be mailed back to iRhythm where the report is generated.

Post system event monitoring device is a newer credit card size “Heart Card” device that a patient carries and when they feel something, they can open the shirt and place the device on the chest.  The strength of this device is that the patient is not attached to a machine and is not required to wear electrodes.  However, a major limitation in this device is that it could miss the onset of abnormal rhythms that give a lot of insight into cardiac problems.  Alive Cor has a sleeve that fits over iPhone or Android phone and patient can place two thumbs on the sleeve and ECG data is recorded and via blue tooth transmitted to the provider.

Loop Cardiac event monitoring devices are preplaced but only record when activated. Patient can wear two electrodes for up to 30 days.  When a patient has symptoms, a patient needs to press a button and record the heart rhythm.  The limitation is that there is no quantification of abnormalities; it only gives qualitative information.  Additionally, it does not record the onset of symptoms.  Some next gen devices save a small amount of information about how the heart was beating when the button was pressed; allowing for some presymptom recording.  This feature is useful for people who may lose consciousness for instance, when they had heart problems and can press the button only after regaining consciousness.  Some newer devices have auto triggers with event monitoring and added algorithms.  They all require landline for transmission of data.  These are generally not for patients with serious, life threatening cardiac arrhythmias.  Medtronic’s implantable Reveal Plus Insertable Loop Recorder, can record ECG up to 3 years.  It is ideal for long term follow up for post-ablation AF patients.  The limitation is that it has to be implanted.  However, next gen device may be so tiny that instead of having to implant it, it might be possible to inject it.

Mobile Telemetry Wireless ECG devices, introduced in early 2000, require no patient interaction to transmit the data.  They have built-in algorithms to detect abnormality and record 2-3 channels of ECG, though a few allow up to 8 channels.    Bondietti’s company BioMedical System’s TruVue wireless ambulatory device is the first mobile system that can transmit ALL of a patient’s ECG during the monitoring period.  It comprises of a sophisticated arrhythmia analysis algorithm with automatic wireless data transimission to provide a comprehensive long term ECG monitoring.  Patient wear sensors around a neck, under a shirt that are connected by electrodes, attached to their chest.  The sensor continuously digitizes a two channel electrocardiogram and transmits it via wireless link technology to a handheld unit that a patient can carry.  Via the cellphone data plan, the handheld unit can transmit every beat of the two channel ECG to secure servers, located at the company’s 24 X 7 monitoring center, staffed by certified cardiac technicians.  A patient may be monitored with this system for a duration of up to 30 days.  This provides a comprehensive long term ECG monitoring solution for patients with ongoing cardiac arrhythmia.

The talk was followed by Q&A.

English: Example of holter ECG software screen shot. (Photo credit: Wikipedia)