Global Sole FDA-Approved pVAD Faces Dual Class I Recalls: Is the Interventional Artificial Heart Market on the Brink of Transformation?

$16.6 Billion: Has Johnson & Johnson Struck Gold?

On November 1 last year, Johnson & Johnson announced the acquisition of all shares of Abiomed for $16.6 billion. If predetermined commercial and clinical trial milestones are achieved in the future, shareholders of Abiomed will also receive an additional cash entitlement of up to $35 per share.

After the acquisition, while Johnson & Johnson has been actively promoting Abiomed's Impella series of percutaneous ventricular assist devices (pVAD), it has also received two Level 1 recall notices.

It is reported that the Class I recall identified by the U.S. FDA is the most serious type of recall, and using devices subject to a Class I recall may cause serious injury or death.

Facing Two Consecutive Class I Recalls, Johnson & Johnson and Abiomed Remain Confident, Not Pulling All Products Back. Why Are Johnson & Johnson and Abiomed So Confident? What Are the Reasons Behind These Two Recalls? What Significant Impacts Do They Have on the Industry and Market?

An interventional artificial heart is an innovative device that can increase blood flow and enhance blood perfusion in different ways while reducing myocardial oxygen consumption.Enhance cardiac pumping function in acute heart failure patients in the short term。

Compared with artificial heart products, interventional artificial hearts can treat patients through minimally invasive intervention, with smaller incisions, less harm, and relatively shorter running support time in the body. They are suitable for acute myocarditis with poor conventional treatment effects, cardiomyopathy with shock, refractory heart failure, cardiogenic shock caused by AMI, and high-risk PCI perioperative support.

It is reported that heart failure associated with interventional artificial hearts represents the end-stage of cardiac disease development, with a five-year mortality rate as high as 30-70%, and is widely recognized as "the last battlefield in the field of cardiovascular diseases."

The Harmfulness of Heart Failure and the Large Number of Patients Have Given Birth to "The Next Blue Ocean." According to public data, there are nearly 30 million heart failure patients globally, and about 10.67 million in China. It is expected that the number of heart failure patients will continue to grow as the survival period of cardiac disease patients extends and the aging population intensifies.

Data released by market research firm ReportLinker shows: the global heart failure treatment device market is expected to reach $14 billion by 2025; the size of China's heart failure management market will exceed 10 billion yuan.

Since switching to the interventional artificial heart track in 2005, Abiomed has continuously expanded the indications for the Impella interventional artificial heart and launched new product models. To date, Impella has become a series of products with various models, including Impella CP, Impella 2.5, Impella 5.0, Impella 5.5, and Impella RP.

Among them, Impella CP, 2.5, 5.0, and 5.5 pump blood directly from the left ventricle through retrograde aortic access; while Impella RP provides hemodynamic support to the right heart system by insertion through the inferior vena cava into the pulmonary artery.

In the global market, limited by the high technical threshold of invasive artificial hearts, only a few companies have made investments, andImpella is the only percutaneous cardiac pump technology currently approved by the U.S. FDA., while invasive artificial hearts from other companies are still in the research and development or clinical registration stage.

The globally unique approved status has brought substantial profits to Abiomed. In the fiscal year 2022, Abiomed's revenue reached 1.03 billion US dollars, of which revenue from Impella amounted to 985 million US dollars, accounting for over 95% of the total revenue. It can be said that Impella almost entirely supports Abiomed's valuation.

In addition,With the Impella series of products, Abiomed became one of the 14 tenfold pharmaceutical stocks in the U.S. stock market from 2009 to 2019.。

In the past few months, the Impella series of products, which have been supporting Abiomed's valuation, have encountered two Level 1 recalls. In June 2023, the FDA issued a Level 1 recall for the Impella 5.5 heart pump, involving 466 devices; in July 2023, the FDA again issued a Level 1 recall for Impella devices.

Despite receiving two consecutive Class I recalls, industry insiders believe that there is no issue with the design of Impella. The proof lies in its cumulative application in over 230,000 cases and the consistent recognition it has received from both clinicians and patients. Moreover, the recall notices did not mention any deaths (clinical incidents) related to the reasons for the recall.

So, what are the reasons for the two Level 1 recalls?

In June 2023, the U.S. FDA issued a Class I recall for the Impella 5.5 with SmartAssist system due to perfusate leakage causing a drop in perfusion pressure and triggering device alarms. If not resolved, it may lead to the heart pump stopping, depriving patients of treatment; if the pump fails, critically ill patients could deteriorate further, experience worsening conditions, and potentially suffer severe harm or death.

In response, Abiomed is recalling the Impella 5.5 with SmartAssist specific kits using a phased replacement approach, replacing all affected pumps in inventory. Meanwhile, Abiomed also stated: "Stricter controls should be enforced during both the operation and sterilization processes, strictly following the Instructions for Use (IFU)."

Based on the lessons learned from this incident, relevant companies in China should promptly standardize the proper operation of their products to reduce adverse events caused by improper handling.

In July 2023, Impella was once again subject to a Class I recall by the U.S. Food and Drug Administration (FDA). The reason is that for patients who have undergone transcatheter aortic valve replacement (TAVR), there is a risk of collision between Impella's rotating impeller and the TAVR implant (distal stent). Such collisions may damage or destroy the impeller blades. A damaged impeller system may reduce blood flow or cause the heart pump to stop functioning, potentially delaying treatment or failing to provide sufficient blood flow support for the patient. For patients requiring high-level support, insufficient blood flow can be life-threatening. Another risk is that fragments from broken blades may enter the vascular system, causing embolism.

In response, Abiomed advises physicians to be mindful of the potential interaction between Impella and TAVR; carefully position the impeller system in TAVR patients. Meanwhile, Abiomed plans to update the system instructions and urges clinicians to avoid repositioning the Impella device while it is rotating.

However, Abiomed does not plan to withdraw the Impella devices. Its statement pointed out: "These devices remain available, and Impella technology can continue to be safely used for patients implanted with TAVR valves."

HearHill commented: "There is no issue with the product itself; the recall was mainly due to surgical operation reasons. In subsequent surgeries, clinicians just need to pay attention to the distance between the Impella heart pump and the TAVR metal stent."

Feng Kaili stated, "We also believe that the main cause is insufficient training in physician education and product usage. In fact, when Feng Kaili initiated the PERSIST-I clinical trial last year, we had already noticed this potential risk, so relevant risk warnings have been included in the product manual."

Overall, the two consecutive Class I recalls have neither affected the indications or scope of use for Impella products, nor impacted their market performance—Impella continues to sell strongly. However, it is worth noting that while Impella has received two Class I recall notices in succession, China's interventional artificial heart enterprises are advancing rapidly, achieving leapfrog development.

The interventional artificial heart is undoubtedly a high-tech, high-threshold track, but there are still a group of innovative companies in China that have made their moves. Among them, XIN HENG RUI, Core Medical, Tongling Biomimetics, HearHill, LifeShield, Sunview Technology, magAssist, and Fengkaili Medical not only completed financing against the trend during the capital winter, but also made rapid progress in the development of related interventional artificial hearts.

For example, the first-generation interventional artificial heart product SynFlow 3.0 from magAssist has entered the clinical trial stage. It completed the PERSIST-I clinical trial in November 2022, entered the special review process for innovative medical devices at the end of last year, and will soon launch the large-scale PERSIST-II trial.

Core Medical's self-developed CorVad interventional ventricular assist system successfully completed its first clinical trial surgery on July 24 and entered the green channel on July 27.

LifeShield Medical, magAssist, and Shengshi Technology have completed their first animal experiments; Tongling Bionic and HearHill are about to commence clinical trials;

XIN HENG RUI, which has just completed its financing, will accelerate the registration and clinical trials of its OmniHeart percutaneous ventricular assist device…

Technically, various companies have chosen different technological approaches and optimized and upgraded their products through differentiated strategies to address the limitations exhibited by Impella products.

Currently, depending on the location of the power unit, interventional artificial hearts are divided into two types: motor built-in and motor external. The widely used Impella 2.5, Impella CP, and Impella 5.0 adopt the motor built-in approach. In contrast, the Impella ECP system, which is still in the research and development stage, adopts the motor external approach.

Among them, companies such as LifeShield Medical and HearHill have adopted the built-in motor technology route. magAssist and Fengkaili Medical have opted for the external motor technology route. Some companies have simultaneously invested in both technology routes.

It is reported that,Intra-ventricular artificial heart products with an integrated motor design feature shorter transmission distances and reduced vibration. Consequently, these intra-ventricular artificial heart products cause less damage to the myocardium and heart valves, provide more stable fluid dynamics, generate fewer vortices, inflict minimal harm on blood cells, and present a lower risk of hemolysis and tissue damage.However, since the motor is placed inside the body, the size of the product is also larger.

Taking LifeShield Medical as an example, the outer diameter of the catheter for its interventional artificial heart is 14Fr. It can access the left ventricle through two peripheral routes: percutaneous femoral artery and axillary artery, providing an average flow rate of 3.0L/minute. This product primarily targets two indications: protection during high-risk PCI procedures and cardiogenic shock, with a usage duration ranging from 2 hours to 3 days.

In terms of the sealing and cooling of micro motors, LifeShield Medical has adopted an innovative "non-perfusion sealing" technology solution. According to reports, the "non-perfusion sealing" technology avoids the potential perfusion fluid leakage issues found in Impella products, helps reduce production process complexity, and cuts costs. During use, clinicians do not need to establish an extracorporeal perfusion pathway, enhancing safety and operability.

Currently, the LifeShield Medical intravascular artificial heart has completed its first animal experiment. The experimental data shows that its hemolysis level is much lower than clinically relevant values, there were no blood clots or thrombosis at key pump locations, and no major clinical complications occurred.

Similarly, VCBeat's biotech subsidiary has also optimized its interventional artificial heart product with a built-in motor design. Not only did they overcome the challenge of integrating a built-in motor with liquid sealing technology, but they also enhanced hemolysis performance by optimizing the power unit and impeller design, surpassing acceptable standards for hemolysis indicators. By reducing hemolysis, they extended the treatment duration of the interventional artificial heart. Additionally, through structural optimization and material selection, they eliminated the risk of the device breaking or leaving residues within the heart chamber.

Based on innovations in micro-motors, low-hemolysis impellers, liquid sealing technology, and a new anticoagulant cooling system, the interventional artificial heart developed by Tongling Bionic has the advantages of low hemolysis, easy operation, and no risk of breakage inside the body.

Compared with the motor-integrated route, the interventional artificial heart products adopting the motor-external route have the advantages of small size, minimal trauma, low bleeding risk, and better postoperative wound recovery.However, it also has the problem of high technical requirements for flexible drive shafts, foldable impellers, etc. Currently, only a few companies globally have mastered such technology.

According to clinical needs, Fengkaili Medical has simultaneously developed in-body motor technology and out-of-body motor technology. Among them, the product based on the out-of-body motor technology route is progressing faster.

According to reports, the interventional artificial heart product of Fengkai Li Medical's extracorporeal motor route has the advantages of small size, no temperature rise, and easy operation, making it more suitable for short-term (hours to days) clinical use. Moreover, as the external motor can be reused, the cost per surgery will be significantly reduced.

Currently, the first-generation interventional artificial heart product SynFlow 3.0 from Fengkaili Medical has entered the clinical trial stage. The first clinical indication is protection for high-risk stent surgery. The PERSIST-I clinical trial has been completed, and the PERSIST-II large-scale trial will be launched soon.

magAssist has also chosen to develop extracorporeal motor technology. According to reports, magAssist mainly focuses on three core indicators—“trauma, flow, and support time”—in the development of its interventional artificial heart. The interventional artificial heart developed by magAssist has an interventional size of 9Fr, which can reduce vascular complications. Its flexible shaft and soft impeller design offer excellent passability, allowing for unobstructed movement through the aortic arch and valves. Additionally, the foldable impeller design provides greater hydraulic efficiency at lower rotational speeds, with a flow rate sufficient to meet the needs of patients with cardiogenic shock.

Currently, magAssist's NyokAssist interventional artificial heart has completed animal experiments in China after the final improvements.

In addition to the aforementioned companies, other enterprises in China have also upgraded and iterated interventional artificial hearts through their own original technologies.

For example, Core Medical's CorVad interventional artificial heart uses built-in axial dual-motor technology, offering advantages such as small size, high flow, low heat generation, long service life, and excellent blood compatibility. Compared with overseas products already on the market, CorVad provides greater flow at the same catheter size. Currently, multiple models of CorVad are under development, providing comprehensive treatment solutions for high-risk clinical patients with different flow requirements and varying support durations, meeting mid- to short-term circulatory support needs.

Shengshi Technology, relying on its numerical simulation and experimental simulation testing technology for hemodynamics, has independently designed and developed several medium- and short-term mechanical circulatory support products, effectively addressing core technical challenges commonly faced by such products, including hemolysis, thrombosis, and poor long-term stability.

XIN HENG RUI's interventional artificial heart product adopts an efficient fluid design, with a flow rate of over 4.0L/min. In terms of blood compatibility, the product’s hemolysis index NIH is 90% lower than the industry standard, causing less damage to blood. Meanwhile, the product’s miniature implantable motor boasts advantages such as small size, high power density, excellent biocompatibility, and high reliability, enabling continuous and stable operation for more than 7 days. Additionally, the product is equipped with an intelligent safety monitoring system, which uses built-in algorithms to determine the position and operating status of the blood pump, enhancing the safety of continuous operation in non-operating room environments (such as ICU and transport), better meeting clinical needs. Currently, this product is applying for the NMPA Innovative Medical Device Special Review Procedure.

As of now, an increasing number of domestically produced interventional artificial hearts are moving from animal experiments to clinical trial stages, and will soon be approved in batches. Only then will the competition in this field truly begin.

Reference: "Global burden of heart failure: a comprehensive and updated review of epidemiology"