
$8 Billion Electrophysiology Market Poised for Potential Shake Up as PFA Technologies Move to the Forefront
A new emerging class of non-invasive catheter based technologies called pulse field ablation (PFA) have the potential to shake up the large and rapidly growing global electrophysiology market for treating atrial fibrillation. The first of these technologies from Boston Scientific (BSX) is already approved in Europe and they are poised to garner FDA approval starting in 2024. Given early safety and efficacy data along with procedural workflow advantages, PFA could become the dominant technology for treating AFIB in coming years and has potential to alter the competitive landscape dramatically.
Atrial fibrillation (AFIB) affects 5-6 million adults in the United States today and given demographic trends is estimated to grow to 12 million adults by 2030 making it one of the highest growth areas in med-tech. In 2022, we believe there were approximately 300,000 ablation procedures to treat AFIB creating a U.S. market of approximately $3.5 billion. Worldwide there are 37 million individuals with AFIB and the world electrophysiology market is estimated to be between $7 and $8 billion and growing at 11% annually. Average device costs for an ablation procedure are approximately $10,500 in the U.S. comprising with the majority of the costs comprising ablation catheters, ICE catheters for cardiac imaging, and mapping catheters. In the U.S., hospitals on average make approximately $21,000 on average for ablation procedures (Medicare average 2023 rate for APC 5213 is $23,841). Pricing is likely to increase with the new class of pulsed field ablation (PFA) catheters coming to market and Medtronic and others have indicated the new PFA technologies will likely sell at a premium to existing thermal devices.
Untreated atrial fibrillation leads to a significantly higher risk of stroke (3-5x), along with higher risk of heart failure, blood clots, and other complications. Atrial fibrillation usually starts as paroxysmal AFIB which is intermittent and progresses to persistent AFIB which is AFIB lasting more than seven days. Treatment for AFIB typically begins with antiarrhythmic drugs and progresses to catheter ablation or MAZE procedures which are open heart ablations usually done in conjunction with open heart surgery for other conditions. Both procedures create scar tissue or burns on the inside of the heart to break up electrical signals that cause the irregular heartbeats associated with AFIB by electrically isolating the pulmonary veins from the left atrium. The current standard of care is non-invasive catheter based cardiac ablation using radiofrequency (RF) thermal energy catheters or a cryoballoon.
Johnson and Johnson’s Biosense Webster division with its THERMOCOOL SMARTTOUCH™ SF catheter (the most commonly used ablation catheter in the world) and Abbott (ABT) have historically dominated the non-invasive electrophysiology market controlling roughly two thirds of all sales. Johnson and Johnson’s total electrophysiology sales are over $4 billion at its current run rate. They are followed by Medtronic (MDT), Boston Scientific (BSX) and smaller players such as Stereotaxis (STXS), Microport CRM (Hong Kong 0853), Biotronik (private), and Catheter Precision (private). Additionally, there are new players emerging into the PFA market such as Kardium, Pulse Bioscience (PLSE), and Adagio Medical.
The primary efficacy endpoint in treating atrial fibrillation through ablation is typically 12-month freedom from atrial fibrillation and atrial flutter. 12-month efficacy for current thermal ablation catheters has stood between 60% to 80% for paroxysmal AFIB and 50% to 60% for persistent AFIB based upon a study published in European Cardiology. After repeat procedures in patients with paroxysmal AFIB the success rate is 85% to 90%.
PFA uses a series of microsecond duration high amplitude electrical pulses that ablate myocardial tissue without significant heating. The technology is believed to have higher tissue specificity leading to less damage to the underlying tissue or neighboring anatomical structures. Median procedure times have also been shown to be shorter. In European clinical experience mean procedure times for PFA were 58 min. versus 82-128 minutes for cryoballoon and 142-162 minutes for point by point RF ablation. Lower procedure times can contribute positively to safety and both hospital and physician economics. Despite shorter procedure times and what appears to be improved safety based upon early data, It is unclear at this point whether PAF technologies will have greater efficacy than traditional thermal ablation catheters as early data has shown similar outcomes.
Medtronic is poised to be one of the first companies to potentially receive U.S. FDA approval for its PulseSelect™ PFA system. The PULSED AF pivotal clinical study, a prospective, single-arm, multicenter trial, the company enrolled 300 total patients, 150 with paroxysmal AFOB and 150 with persistent AFIB. The study met both its primary safety and efficacy endpoints with one of the lowest rates of adverse event rates seen in ablation catheters to date at 0.7%. However, 12-month efficacy endpoints of 66% for paroxysmal AFIB and 55% for persistent AFIB are in-line with traditional thermal ablation techniques. There has been hope that PAF technologies could have higher efficacy rates than traditional thermal ablation catheters.
In March Medtronic received CE Mark for its Affera™ Mapping and Ablation system. The system allows for the integration of the Sphere-9 PFA catheter, RF ablation catheter, and high-density mapping catheter which maps arrythmias and provides real time feedback through its navigation and mapping software. Speaking to this advantage, Khaldoun Tarakji, M.D., MPH, vice president, chief medical officer, Cardiac Ablation Solutions business at Medtronic stated. “Current technologies require the use of separate HD mapping and ablation catheters. The ability to map, ablate, and validate with the Sphere-9 Catheter enables the physician to eliminate the need to exchange catheters and empowers them to choose the energy source, whether RF or PF, based on the patient’s needs. All this leads to improving efficiency and most importantly, enhancing the safety of ablation procedures for our patients.” The combination of the PulseSelect™ PFA system and the Sphere-9™ mapping and ablation catheter will allow Medtronic to have a fully complementary suite of PFA technologies with an ease-of-use advantage that does not require intraprocedural catheter switching. Medtronic’s SPHERE Per-AF registration study for its Sphere-9™ catheter and Affera™ Mapping and Ablation system is supposed to enroll 477 patients is scheduled to complete enrollment in late 2023.
Boston Scientific who acquired FARAPULSE™ in 2021 appears to be slightly behind Medtronic in the U.S. market from a timing perspective but was the first to have real world clinical experience as its device received a CE Mark in Europe in 2021. The company is running two separate registration studies for its FARAPULSE™ Pulse Field Ablation System. First is ADVENT, a 900-patient randomized clinical trial in paroxysmal AFIB and The company provided results in August at the European Society of Cardiology conference showing similar outcomes to Medtronic with overall efficacy similar to Medtronic. Treatment success was 73.3% in the PFA arm of the study and 71.3% in the thermal arm, which met the primary efficacy endpoint. Unlike the single-arm studies utilized by most competitors, ADVENT is a multi-arm study and compared to standard of care ablation in patients with paroxysmal atrial fibrillation. There was hope the results would allow the company to claim superiority, especially as the company takes on current market leaders Johnson & Johnson and Abbott. The second study being run by Boston Scientific is ADVANTAGE AF which looks to recruit 417 patients with persistent AFIB and is scheduled to read out in the second half of 2024.
In May Boston Scientific reported data from the 1,200 patient EU-PORIA registration study which looked at data from seven high volume European centers. The study demonstrated a 74% overall freedom from recurrence of AFIB and atrial tachycardia and was 80% in patients with paroxysmal AFIB and 66% in patients with persistent AFIB. This data is on the high-end of what is typically seen with ablation technologies and provides further credence to its superiority claim versus traditional thermal technologies.
Johnson & Johnson is poised to come to market with the VARIPULSE™ Catheter and TRUPULSE™ generator. In February 2023, the company presented early data from its inspIRE European pivotal clinical trial that evaluated 226 patients with paroxysmal AFIB. In the study, 71% 12 month effectiveness was achieved with zero adverse events after procedural modifications were made in the first cohort. Johnson & Johnson’s U.S. registration study AdmIRE, is enrolling 362 patients with paroxysmal AFIB and is expected to read out in the first half of 2024.
Like Medtronic, Johnson & Johnson is also betting that the ability to deliver dual energy sources with a single platform will be a market differentiator. In March 2023 Johnson & Johnson initiated their smartfIRE clinical study to evaluate their THERMOCOOL SMARTTOUCH® SF dual energy catheter which will be able to deliver both PFA and RF energy. Describing the importance of this dual energy capability, Celine Martin, Company Group Chairman, Cardiovascular & Specialty Solutions Group at Johnson & Johnson, “As a long-standing leader in the field of cardiac ablation, we are working to bring forward a versatile, best-in-class portfolio of pulsed field ablation solutions – complementary to our radiofrequency ablation catheter portfolio – to address various ablation strategies in the treatment of atrial arrhythmias.” The smartfIRE study is scheduled to enroll 149 participants and be completed in the second half of 2024.
Noticeably absent from the PFA race is Abbott, who has a $1.9 billion electrophysiology business. The company is taking a wait and see approach to the market betting the early technologies will have flaws. The Company is developing a technology called Volt, but it is several years behind PFA market leaders. Abbott’s EnSite X is one of the market leading mapping catheter systems, which are not needed by the newer PFA technologies which have integrated mapping technologies. It is possible that Abbott could look to M&A to bolster its portfolio and speed time to market.
Along with the heavyweight med-tech players, smaller competitors are also in the hunt with PFA technologies including Pulse Biosciences (PLSE), and private companies Kardium and Adagio Medical. Pulse Bioscience has a nanosecond pulse field ablation technology which it believes could differentiate versus existing technologies by preventing the need for heavy sedation and paralytics and potentially improving outcomes. The company has partnered with CardioNXT’s mapping to integrate its iMap system for 3-D mapping and navigation. To date the companies have only completed preclinical studies.
Kardium plans to market its Globe Pulse Field Mapping and Ablation System. The technology incorporates high-definition mapping and single-shot PFA ablation in a single catheter. The company believe the ability to not have to reposition the catheter multiple times in each pulmonary vein during the procedure. The company began it’s U.S. IDE study called PULSAR with the first patients treated in May. It is enrolling patients with both paroxysmal and persistent AFIB and scheduled to read out in early 2025.
Adagio Medical is currently running its PARALLEL clinical study evaluating the safety and efficacy of its CryoPulse™ PFCA catheter in combination with proprietary PFA and iCLAS™ cryoablation consoles. The study which will enroll 78 patients and randomize between the two technologies is scheduled to be completed in the second half of 2024.
Given early data and procedural advanatages, PFA technologies appear poised to shake up the $8 billion global electrophysiology market. Based upon results to date and market positioning, it appears that Boston Scientific, a relatively small player in the space today, and Medtronic could be poised to be the biggest beneficiary of this trend if PFA technologies begin to transition to the standard of care for the treatment of atrial fibrillation.