CorWave: The Natural Evolution of Technology

Last month, RW spoke with Charlotte Rasser, Ph.D., Strategy & Scientific Affairs Manager at CorWave, an exciting French medtech start-up that develops innovative cardiac assist devices for heart failure patients. CorWave’s implantable blood pumps are based on a breakthrough membrane technology. CorWave was founded in 2012 by the start-up studio MD Start and is funded by investors including Bpifrance, EIC Fund, Financière Arbevel, M&L Healthcare, Novo Holdings, Seventure, Sofinnova Partners, and Ysios. The company has secured €80 million of equity and nondilutive financing and currently employs over fifty people.??????????????

Above is the CorWave SA LVAD???????????????????????????????

Heart pumps may sound like a futuristic phenomenon, but these devices have been widely used in clinical settings for many decades now. Initially designed as a bridge to a heart transplant when a patient’s own heart was too weak, these devices provide blood flow to the body and allow the patients to get stronger with an improved quality of life. They are now widely utilised as a valuable form of treatment, presenting end-stage heart failure patients with the priceless gift of more time; however, they also carry significant risks to the patient. Over 70% of patients implanted with heart pump will be re-hospitalized with a major complication, such as stroke, infection, or bleeding, within one year.

Cardiovascular disease is the leading cause of death globally, taking an estimated 17.9 million lives each year (based on the latest statistics provided by the World Health Organisation). The rising prevalence of this disease, along with long waiting periods for heart transplants, have offered growth opportunities in the market during the forecast period. The heart assist device market is projected to reach USD 5.5 billion by 2026 from USD 2.1 billion in 2021, at a CAGR of 21.6% from 2021 to 2026, and this is backed by increasing investments, funds, and grants for research on heart failure treatment.

CorWave's breakthrough technology differs from today's commercially available heart pumps (or “LVADs”, for “left ventricular assist devices”) by its physiological operation, including the ability to mimic the pulse and blood flow rates of a healthy heart, and ultimately, CorWave's membrane pump technology is expected to reduce the complications associated with the current devices and to improve the management of heart failure patients.

At the core of the CorWave products, ‘CorWave LVAD’ and ‘Nemo’, is the disruptive and patented pumping technology known as ‘The Wave Membrane’. The membrane is the result of more than 20 years of research and development. This disruptive technology radically differentiates CorWave’s products from commercially available LVADs based on a rotary pump technology, and uniquely allows CorWave LVAD and Nemo to provide physiological blood flow. Utilizing this technology, CorWave LVAD restores blood flow while generating high fidelity pulsatility, unlike continuous-flow rotary pumps which dampen the native pulse so much that patients literally do not have a pulse. The CorWave pump operation is like that of the native heart: it can faithfully recreate the ejection (systole) and filling (diastole) phases without exposing the blood to high shear conditions.

Above is the CorWave SA Wave Membrane Technology

CorWave has taken inspiration from nature to tackle heart failure, with the technology inspired by the undulating motion of marine animals to generate blood flow. This movement provides an efficient way for the animals to move fluid, propelling them through water. In CorWave’s pumps, a polymer membrane reproduces a similar, though reversed, interaction: the membrane is fixed, and the fluid (blood) is propelled. The movement can be produced with different membrane geometries, specifically, a discoidal shape and a rectangular shape. Both of CorWave’s ‘wave-membrane pumps’ are driven by an electromagnetic actuator, which generates the oscillations of the polymer membrane. These oscillations trigger the propagation of circular concentric waves along the membrane (like a sound-speaker), which drives the propulsion of blood.

Having recently seen CorWave announce that it has completed the first 90-day preclinical study to evaluate its left ventricular assist device operating synchronously with the native heart without the use of sensors, we were intrigued to hear some more about the company from the perspective of its Strategy & Scientific Affairs Manager.

“CorWave was founded in 2012, by a start-up studio called MD Start. The idea was to use our Wave Membrane technology to develop heart assist pumps. It’s a biomimetic technology based on a polymer membrane. The company progressively grew to a 1300 square meter building hosting our R&D centre, with laboratories, design offices, etc. It’s been almost 10 years

In medtech, the development times are usually long, and times in the cardiac pump industry are exceptionally long. Typically, in this industry, it takes around 10 to 15 years to get a project from the beginning to clinical use, so that’s the kind of timeline we’re looking at.”

At what stage is CorWave right now?

“We’re still at the preclinical level, and to prepare for the upcoming clinical phase, we’ve recently hired a VP of Regulatory, Quality and Clinical Affairs. Having someone with experience in this domain, who has contributed to over 10 or 15 trials and gained approvals for many devices in the cardiovascular device space, will be highly beneficial in our future growth.

We’ve also hired a VP of Manufacturing to prepare for industrialisation, transforming our prototypes into medical devices prepared in a qualified environment.”

You mentioned the wave membrane technology, could you explain how that powers the LVAD device?

“It works in the same way that a fish or eel swims in water, creating movement by undulating. In our case, we have a flexible membrane which undulates. The membrane is fixed at one extremity, so instead of the membrane moving in the fluid, it’s the fluid that moves in the opposite direction, so that we can create the flow of the heart pump.”????????????????????????????????????????????????

How is that wave membrane technology beneficial in comparison to those of competitors?

“Current cardiac pumps are based on a rotary technology. They are reliable and small enough to be implanted next to the heart but the price that the patients must pay is that the flow that is produced is almost constant. The patients don’t have a pulse anymore. This lack of pulse has consequences on the body, and it is associated with a number of severe complications (stroke, gastrointestinal bleeding…) which are the main limitation of these devices.

Besides, when a healthy person exercises, their heart can generate a blood flow that is four times higher than that of a resting state. Patients with current cardiac pumps don’t have these differences in blood flow, so they still suffer from heart failure symptoms when they exercise. With the wave membrane technology, we’re able to generate a flow that follows the heart, to recreate a pulse and adapt to patients’ needs when they exercise.”

I understand that for patients who aren’t eligible for the LVAD device, you also have the Nemo device?

“Yes, that’s the second product we’re developing, although right now we’re focusing on CorWave LVAD. Nemo is smaller and is designed to be placed on the chest, just under the skin, so you don’t need to open the heart to implant it. It is linked to the heart by a catheter that is put through the vessels, so the implantation is less invasive than that of an LVAD. It has less flow capacity, so it’s not for the patients who need full support. LVADs need to provide at least 5 litres per minute of blood flow in typical pressure conditions because that’s what is needed for full support. With Nemo, we provide less than that, it is a solution for patients who have less advanced, or different types of heart failure.”

Above is the CorWave SA Nemo

So, for both of those devices or more specifically the LVAD device, what are the expansion plans? How do you go about gaining FDA approval/CE marking?

“We will conduct clinical trials in Europe and the US. There is no exact time frame for this as of now, but we are really focusing on completing the development of CorWave LVAD to offer a device to clinicians and patients that is safe and fulfils all its promises.”

There is much medtech innovation currently occurring in France, what do you think the key drivers are for this?

“There are many different aspects, but the collaboration between clinicians, researchers, and entrepreneurs is key. We see a lot of projects that come from clinicians and inventors getting together to build innovations. In France, we feel that the government sees this as a priority so there are efforts being made to provide adequate funding in this area.”

Are Total Artificial Hearts something that CorWave plans to develop in the future?

“Not necessarily any time soon. But what can be used in the field is BiVADs, which is when two LVADs are attached to the heart (one to each ventricle), where you don’t replace the heart, but you assist both ventricles. CorWave LVAD is meant for the left ventricle of the heart because in most cases it’s the one that fails first. In some cases, an LVAD can be used as an RVAD, to support the right ventricle by making a small adjustment to the LVAD. So, in the future, these are possibilities for how our device can be used, but currently, it’s not an indication we are looking at.”

So, what adaptation would need to be made for the LVAD to be used on the right ventricle?

“The main thing is adjusting the setting because you need less power on the right ventricle, which is smaller, and pumps the blood only to the lungs, whereas the left ventricle pumps the blood to the whole body. So that’s a software setting but you need to be sure that the pump works well at this setting. The second thing is that the right ventricle is anatomically smaller. The LVAD has an inflow cannula, a tube that goes into the ventricle to get the blood, which is then accelerated in the pump and goes out into the aorta, the artery that goes out of the heart. The inflow cannula has the correct dimensions for the left ventricle but if you put it on the right ventricle, you would want it to be slightly shorter. What surgeons do is usually put a few rings of felt around the cannula, outside of the ventricle so that the length of the cannula inside the right ventricle is smaller. So, a small surgery trick is required to make this change.”

Interesting – could you explain the LVAD implantation procedure in a little more detail for our readers?

“Yes. So, the surgeon needs access to the heart. The most common procedure is a sternotomy: you open the sternum with a long incision. Then, you sew what’s called a sewing ring on the apex of the heart (bottom of the left ventricle) and once that’s secured, you make a hole in the heart muscle, within the sewing ring. Following this, you secure the pump to this ring, with the inlet cannula going into the left ventricle. Finally, to get the blood from the pump to the aorta, you sew an artificial vessel from the pump to the aorta.”

It was a pleasure speaking with Charlotte and gaining a greater insight into CorWave’s fascinating Wave Membrane technology, that certainly sets their LVAD and Nemo devices apart from competitors in the field. Through its international team of excellence that has achieved critical R&D milestones, the company has positioned itself to one day seize a portion of the pie in a multi-billion-dollar market. At RW Search we eagerly await CorWave’s continual progression in the field as they develop through the pre-clinical stage of their ground-breaking devices.