Alucent Biomedical Re-Envisioning PAD Treatment with a Natural Vascular Scaffold
Start-up Alucent Biomedical is using a light-activated molecule, delivered via a balloon catheter, to create a natural vascular scaffold in diseased peripheral vessels, with the aim of providing a long-lasting treatment option that maintains patency while leaving nothing behind in the vessel.
Alucent Biomedical Inc. is rethinking peripheral artery disease (PAD) treatment with a novel natural scaffolding technology based on a light-activated drug therapy delivered via a balloon catheter. This first-of-its-kind drug-device therapy, known as Natural Vascular Scaffolding (AlucentNVS), is designed to provide a more natural and effective way of establishing and maintaining arterial patency in the lower extremities compared with existing treatments such as stents and traditional drug-coated balloons; essentially accomplishing “stenting without a stent.” According to company CEO Myles Greenberg, MD, the overarching goal is to avoid the common follow-on complications associated with permanent metal stents, such as restenosis and reintervention; to “open the vessel but not do anything to it that’s going to cause it to close down later.”
Alucent’s NVS Vessel Restoration System with Photoactivated Linking is an all-inone system—including a drug-coated angioplasty balloon and light fiber—that combines standard angioplasty techniques with light-activated protein linking. The procedure begins by inflating the drugcoated catheter at the lesion site. As is the case with all balloon angioplasty catheters, when the catheter is inflated in the vessel it breaks the natural links within the native collagen and elastin fibers that serve as the structural proteins in the vessel wall. At that point, while the balloon is inflated and the vessel is open, the light-activated drug coated onto the balloon’s surface diffuses into the disrupted tissue. A light fiber is then illuminated within the vessel, activating the drug, which acts as a catalyst to reform new linkages in the native collagen and elastin in this open position, essentially creating a natural scaffold, or a natural “stent,” that holds the vessel open. Following the procedure, the light-activated drug is rapidly metabolized and eliminated by the body, Greenberg says.
Because the therapy leaves no foreign material behind, nor does it leave a disrupted vessel wall as does standard angioplasty, the hope is that the arterial wall will retain its natural function and flexibility and there will be no proinflammatory response that can lead to restenosis and retreatment. “One of the beauties of this therapy,” notes Greenberg, “is that we don’t actually change the biomechanics of the vessel. That was critically important to us,” he adds, “because the downstream negative effects of both stenting and angioplasty are likely due, at least in part, to the fact that they massively perturb the natural biomechanics of the vessel.”
The company has done extensive preclinical work investigating this issue, says Greenberg, and has found no evidence that AlucentNVS causes changes to the natural vessel stiffness; nor does it change the endothelial cells themselves, unlike some drug-device therapies in use today, such as paclitaxelcoated balloons (paclitaxel is a cytotoxic drug). “We have shown in a number of preclinical studies that we do not induce the same proinflammatory response as naked angioplasty or metal stents,” he says, noting that a chronic atherosclerotic animal model demonstrated that the treatment was able to keep the vessel open and did not induce restenosis. “So empirically, at least with the model we’ve studied, we’re not having the same deleterious effect as current therapy.”
Moreover, Greenberg notes that based on human cadaver testing, the treatment appears to be effective even in calcified vessels, which are among the most difficult PAD lesions to treat. “We have demonstrated in those cadaver models that by using simple pre-dilation of the lesion, which is a common practice, we get adequate penetration of our therapy into those calcified vessels.” And, although this has not yet been studied in clinical trials, other vessel preparation techniques, such as debulking with atherectomy, could also be employed pre-procedure in highly calcified vessels, he says.
The bottom line, notes Greenberg, is the technology should fit easily into the existing PAD workflow. “This is a very easy-to-use device,” he explains, noting it looks very similar to existing drug-coated balloons, although its mechanism of action is very different. And the process of using it is “quite simple,” he adds. “You put a standard wire across the lesion, as you normally would, insert the device, blow up the balloon, turn on the light for 60 seconds, and then deflate and remove the catheter.”
In May 2020, Alucent initiated a small, Phase I human safety study (ACTIVATE I) of NVS for PAD in the superficial femoral and/or proximal popliteal artery; that study is partly enrolled and will likely need to await resolution of the COVID-19 pandemic before completion. A larger, multicenter efficacy study—ACTIVATE II, testing a commercial version of the system—could begin by mid-2021. That will be followed by a pivotal study for US regulatory approval, which will involve a CDRH-led PMA combination product regulatory pathway.
The company is also developing a version of the device for use below-the-knee and hopes to begin a feasibility study of that system in the next few years. It is also in the early stages of developing the therapyfor the assisted maturation and ongoing usability of arterio-venous (AV) fistulas in dialysis patients, with a first-in-human trial for that application currently targeted for early 2022. In fact, notes Greenberg, there are numerous clinical areas that potentially could benefit from the technology. For example, one of the more interesting potential opportunities the company has identified involves preventing progression of abdominal aortic aneurysms.
The PAD opportunity alone represents a $3.2 billion global market, the firm says, with the majority of that in the US (see Figure 1). And it is a particularly underserved clinical area, with failure rates of up to 50% or greater in realworld lesions treated with existing angioplasty and stenting technologies, resulting in many potentially preventable limb amputations every year.
The next few years will be critical for Alucent as it ramps up its clinical trial program. If successful, the company will fulfill a promise several years in the making, and one with a somewhat convoluted history. The photoactive chemistry behind NVS was originally conceived by Ron Utecht, PhD, who initially started a company called Photobiomed that was acquired by Avera Health, a South Dakota healthcare system. At the time, Avera established a subsidiary, Alumend, to research the technology for various applications, and the vascular field was quickly identified as the best nearterm opportunity. The Avera Research Institute, in collaboration with Utecht, then founded Alucent Biomedical to focus on applications for NVS in the vasculature, and in 2017, Alucent became a standalone company (Utecht continues to serve on the company’s Scientific Advisory Board). Alucent has an exclusive license to nine issued US and foreign patents granted to Alumend, with several more patents pending on the technology.
Avera continued as Alucent’s sole owner and investor until the fall of 2020 when Alucent closed on a $35 million Series B financing led by two new investors: an unnamed large, multinational strategic as well as Fresenius Medical Care Ventures. The Series B brings Alucent’s total raise to date to about $60 million.
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