Cerebral protection developer Claret Medical recently won FDA de novo clearance for its Sentinel device designed to trap blood clots and prevent stroke during heart valve replacement procedures.

The Sentinel uses a pair of filters, 1 in the brachiocephalic artery another in the left common carotid artery, to trap debris released during transcatheter aortic valve replacement that could cause a cerebral embolism.

The device has seen a rough road to approval, however, after missing the primary efficacy endpoint in its pivotal trial. Despite that, the device saw nearly unanimous support from an FDA advisory panel and was cleared by agency.

The clearance is the 1st for such a device from the FDA, according to CEO Azin Parhizgar, who spoke to MassDevice.com about what the approval means, and what’s next for the cerebral protection developer.

Below, edited for clarity, is a transcript of our conversation.

MassDevice: You’ve won FDA De Novo clearance for your Sentinel TAVR filter – what does that mean for your team and Claret and where will you go next?

Azin: With any new technology, you target your markets. You have a cadence in terms of going to market, especially in the healthcare space. You have regulatory boundaries around you, and you work to clear them efficiently.

One of the biggest markets in the world is the US market, so being cleared in the US market opens up a large opportunity for the company, and for the technology. It validates the use and beneficial effects of the Sentinel, because we have conducted one of the most rigorous studies to date, and navigated the river of FDA currents. So it’s one of the biggest milestones for the company so far.

MassDevice: What are your plans for a market release?

Azin: The plan is to have a cadenced launch that would assure the safe use of the device, first and foremost. Any novel technology requires some level of training, to make sure that clinicians use the device not only with respect to the correct intended use, but also that they go through the learning curve of how to handle and use the device.

So, the initial plan is to limit the launch to the IDE trial sites in the US – and that’s up to 17 centers. We chose those IDE centers when we started the trial, as they were centers of excellence for TAVR. So, that has given us a leg up in terms of having made our way into these centers that are already very experienced in TAVR and handle a high volume of procedures.

So that’s the initial launch plan – to carefully launch into those centers of excellence, and then evaluate the pricing and work on the reimbursement at the same time. Then once the company achieves an established footprint in the US, the decision will be whether there should be an exit, or whether we move into a full market launch to realize the full value of the technology in the marketplace, which is the intent of the company if we decide to stay independent.

MassDevice: To step back for a moment, the company’s pivotal trial of the Sentinel device failed to meet its efficacy endpoints, but still gained nearly unanimous support from an FDA panel for approval.  In retrospect, are you looking at that as a study design issue, or is there something else to consider in terms of those efficacy results?

Azin: Very good question.  So, as you mentioned, we had a pretty much unanimous vote of approval from the panel.  And the panel was actually – and I have enough experience with panels and tenure in this industry to say – one of the largest and most rigorous panels that I’ve ever encountered.

The study failed the primary efficacy endpoint, which was a surrogate imaging endpoint. And it was a surrogate endpoint that was not quite validated in this field. It was a very difficult and challenging endpoint because it’s MRI imaging-based with a short window of acquisition.

The primary reason it failed was because the study became underpowered based on the observed variance in the surrogacy endpoint for a number of study logistical issues. However, as we delved into the secondary and post-hoc analyses, that’s when the precision of the treatment effect started to be unveiled, which was the clinical impact of the device on neurological outcomes.

The key data and the key benefit that the clinicians want to see with a device of this type is clinical benefit. And we’re demonstrating very clearly that there’s a greater than 60% treatment effect, in terms of stroke reduction, during the acute period post-procedure. This is when embolic protection devices of this type are the most effective, and that’s the only time that they’re effective, because, by definition, they’re temporary and after the procedure is done you remove them. So, the impact of using that device is primarily post-procedural, and procedural.

In my experience, there are very few treatments, device or drugs, that show a treatment effect of 60% plus.  Although the surrogate imaging endpoint did show a 42% difference,  it just didn’t hit statistical significance, based on it being underpowered.

If you look at the totality of the evidence that we produced, it was very compelling – capturing and removing debris in 99% of the patients, with the size of debris that we captured indicative of causing blockages of intracerebral vessels. All of that data in totality gave a pretty impressive level of confidence to the panel, and, ultimately, to the FDA to clear the device.

It’s important to note that stroke reduction is actually in the device labeling.  When FDA allows you to put your post-hoc data into the label, it’s significant. So, I find that’s one of the most impressive aspects of the clearance.

MassDevice: Your device has been cleared in the EU for 3 years – what sort of post-market data and information do you have on the device from that region?

Azin:  The post-market data in Europe shows a wealth of positive performance data. We have been physically capturing debris – that’s one of the modes of action for the device – which differentiates us from the competition because you can visually see what you’re collecting and removing. With other devices you cannot actually assess the debris since they do not capture the material. With other devices, because debris are deflected, you can bring them downstream to other end organs. We, on the other hand, actually do capture and remove them.

We see consistent data from Europe, and we did a post-market study in about 250 patients.  We saw data that was consistent with what we saw in US, that more than 95% of the patients had debris captured and removed. This should translate to the same type of stroke benefits that we’re seeing in the US study.

Lastly, in Europe, there’s a study that has not yet been published but we presented it at the FDA panel. The study encompasses more than 580 patients and was not sponsored by Claret, and is one of the most impressive sets of outcomes data that we have.  The study shows a 70% reduction in stroke and death at 7 days when you use Claret embolic protection.

So, there are 2 powerful studies that are indicating the same level of neurological benefits that TAVR patients can realize from the use of our embolic protection devices.

MassDevice: So, what’s next in the pipeline for the Sentinel device?

Azin: At this point, the device is very well vetted in terms of its safety and efficacy. So we’re going to focus primarily on the launch and adoption of this device in the US market and continued adoption in the European market. The secondary focus of the Company is on reimbursement from CMS (Centers for Medicare & Medicaid).

We are working hard to bring reimbursement to fruition, and we believe there will be two things driving both adoption and reimbursement of this technology. The first driver of the adoption, I believe, is going to be patients actively asking for the device to protect them from stroke. There have been surveys of patients indicating that the majority of patients fear debilitating stroke, or any stroke, more than death itself.

So, they will demand this device once they sit down with their physicians and go through the risk sharing information as part of informed consent process.  Physicians will have to discuss with the patient that there is a device available that can reduce your risk of procedural stroke by more than 60%, and ask if they want it used in their procedure. So, more and more patients will demand the device.

The second driver is to focus on getting supplemental reimbursement, so that it can help the adoption of the technology more and more.  TAVR is still a pretty expensive procedure because there are only 2 players in the US market, Medtronic and Edwards, and both have premium pricing.

The prices will eventually erode, as all technologies do once more competition comes into the market. So, supplemental reimbursement will be important for us, but not essential due to better TAVR margins eventually. That’s the plan for US, for the foreseeable future.

MassDevice: Anything else to say about Claret Medical?

Azin: What is really important for us, as a company, is that we are the 1st and only embolic protection device for TAVR that has been cleared in the US. This gives us a first mover advantage and a tremendous competitive edge. The next closest competitor in the States is more than 18 to 24 months behind us. They are still in their IDE trial enrollment phase in the US.

And these trials are very difficult because they’re rigorous and include a variety of assessments  – MRI, neurological assessments – and are tough to conduct. And I believe that Claret has done one of the landmark studies of its kind in this space.

So, by virtue of being the front runner, and the only one in the market, Claret has a tremendous opportunity to really open up this space. The fact that we have a very clear clinical benefit should not only help the company thrive, but also help the patient and the physician thrive.