The numbers on pulmonary disease in the U.S are staggering – more than 203,000 people were diagnosed in 2007 alone, according to the Centers for Disease Control, which lists nearly 160,000 lung cancer deaths for that year.
Add in other pulmonary afflictions like chronic obstructive pulmonary disease (126,000 deaths in 2005, according to the CDC) and the numbers pass from staggering to mind-boggling.
That’s the space that Sanovas Inc. and its VAS Zeppelin hope to address, according to CEO Larry Gerrans. We sat down with Gerrans, who co-founded the firm in 2002, to discuss his company’s catheter-based platform and why he thinks it’s about to revolutionize the treatment of lung diseases
Gerrans and his team put the addressable patient population, people with pulmonary disease, at 47 million in the U.S. alone and another 96 million at risk. Add industrializing nations such as India and China, where widespread smoking and pollution create millions more cases, and the market assumes astronomical proportions. In the U.S., that could mean a $3.8 billion market this year alone, according to statistics cited on the Sanovas website.
Gerrans told us that the VAS Zeppelin platform actually consists of five technologies involving imaging, catheter-based access and intervention, "smart" technology and drug delivery – all on a scale small enough to fit into the 1mm to 3mm commonly found in the lungs outer reaches. It’s designed to eliminate the need to crack open patients’ chests to access the lungs – and the 7-day in-hospital recovery time for such procedures.
MassDevice: Give us your elevator pitch for Sanovas.
Larry Gerrans: Sanovas is a company that was inspired by the founders and the pioneers of minimally invasive surgery. We’re the guys who developed the endoscopic camera, the first three chip camera.
We developed a lot of the core technologies and surgical techniques and implant systems for laparoscopy, arthroscopy and looked to the pulmonary anatomy to develop the next evolution of technologies for under 1mm to 3mm dimensions. Over about 10 years of development and initiative and tenacity, we’ve arrived at a platform of five technologies that allows us to see the anatomy, we’ve developed and advanced the access technologies, catheter-based access intervention capabilities and we’ve made catheters smarter.
We’ve also developed physiologic metrics and biofeedback to give us better information and provide doctors with the more intuitive command of the operation environment. And we’ve developed the diagnostic capabilities to diagnose the disease and what we call "therapy enabling technologies" for resection, the ability to resect these tumors.
And more importantly, and finally, is a drug delivery capability that allows us to deliver drugs to the submucosal tumors that reside outside the airway.
So for us, over the last 10 years, working with a lot of the intervention pulmonologists that are out there, it’s been an iterative process of design and development to understand what it is that these guys need and the tools that they need to overcome the complexities of operating on the airways. The airways and the lungs are the last frontier of innovation and intervention – simply because you cannot turn them off in order to operate on them. Unlike a heart that you can "turn off," you can open the chest and do bypasses or valve repairs and valve replacements, put it all back together, hit it with the paddles and turn it on.
You can’t perfuse and you can’t bypass the lungs. You have to work on a vital organ, a breathing organ, a moving organ. Consequently there’s a lot of complexity for us to overcome, one of which was the miniaturization of the technologies to get into the spaces of the lungs and visualize them when you get there.
Two, the ability to acquire diagnostic information that was meaningful, no longer just taking epithelial cell samples to determine whether or not you’ve got cancer. Doctors want significant samples so that they can acquire meaningful biopsies for immunologies. And with personalized medicine on the horizon, especially with lung cancer, it’s important. So we’ve developed some core technologies for that.
And then often when you’re in the lungs, you encounter these obstructions that preclude the patient from breathing, and so you want to be able to remove those. It’s been a delicate process to try to do that, because the capillary blood supply in the lungs is part of the O2 exchange. So when you hit it, it bleeds, and an unfortunate reaction is that a patient goes into a diaphragmatic spasm (which is the body’s primal response to the recognition that its suffocating under the duress and inhalation of all these fluids) and is coming off the table. It’s traumatic for everyone to see and it’s tragic for the patient.
Interventional pulmonology and thoracic surgeons have long just preventively medicated these patients, sent them to the hospital or waited for the disease to progress to a point where they could justify going in an cutting and swapping out a patch of the lung, and that’s just bad medicine.
So really what we were inspired to do is to advance the agenda, to advance the capability and that science, given the complexity of the lungs. We developed a platform of technologies that gives doctors not just a tool but a tool belt, and also some new innovations that give us broad application across tubular anatomy. We’re pretty excited about that, because we’ve now got applications in cardiovascular, neurovascular, ENT, GI, general urology. Anywhere you’ve got a tubular anatomy, we’re playing in that space.
Our core focus right now is interventional pulmonology and that’s where we’re going to work to deliver the technologies because there’s an urgent humanitarian need.
MassDevice: Can you dive a bit deeper into the physiologic metrics and biofeedback technologies Sanovas has developed?
LG: The physiosense technology is revolutionary because it provides the doctor with the physiologic metrics to understand what the elasticity of the vessel walls are, understand the densities of the obstructions they’re facing, the diameters of the anatomy they’re in. We take all of that information and we take an algorithm that controls the resection modality to remove the tumors organically.
One of the problems with current methods is that, in order to go into the lungs, doctors have to have the cautery with them, they have to have their laser with them, because if it starts to bleed, they want to fry it. The problem with that, in most cases, is that they actually use the laser and use the cautery to break down the obstructions, but the problem is that these treatments create vaporous discharge. That gets ingested into the blood stream, creates an embolism which results in a stroke, and maybe death. It’s consequential. It’s a big risk, it’s a big problem. So really, effectively what we try to do is just de-risk the procedure and give these guys the ability to control the operative environment to get in and do what they’ve got to do.
So with PhysioSense, we can take those metrics that we acquire in real time, milliseconds, and then render and three-dimensionally image the anatomy on a monitor so they can actually see the evolution of the change and the treatment as it goes.
MassDevice: How long have these platforms been in development at Sanovas?
LG: We’ve been at it for about 18 months now. We did a lot of design/development, really listened to the community, and really got our minds around the right approach. Once we had the consensus among the physicians about what the technologies were that they wanted, that they needed, that they felt had value, we narrowed the scope and we focused on the development of those five core technologies.
So that’s been the initiative the last 18 months. Part of that was just an inspirational pursuit of information and feedback and inquiry and perseverance.
MassDevice: Where are you on the regulatory pathway?
LG: We’re heading into regulatory right now, we’ve got very strong FDA counsel. We’re working with [law firm] King & Spalding, we’ve got Ed Basile, who was a former associate chief counsel at the FDA. And so we’re definitely talking about making sure we’ve got the right pathway.
MassDevice: You’re going to roll out in the U.S. first?
LG: We’re going to roll out in the U.S. first, then we’re going to go EU, or CE Mark in concert, simply because it’s a comparable process, there’s no reason to do one and then the other. We’ve got a lot of confidence in the FDA still, but we also have a lot of confidence in our technologies and we also have confidence in the intellectual talent that we’ve got behind our FDA initiative. We worked very hard to bring on the best minds, the best talents. We’ve got Dr. Beverly Lorell, who is our FDA liaison. She’s the former chief medical officer for Guidant, she’s been a practicing cardiologist for 25 years and is a professor at Harvard. She’s a really, really smart lady and she really understands the process and she understands the technology.
But for us to achieve revenue and to get the company going, and to really deliver the technologies that are needed right now and to meet the urgency of the need that’s in the space, we can deliver imaging capability, we can deliver the tumor resection capability. And then the drug delivery is something that’s obviously going to have to undergo the scrutiny of the FDA.
We really believe that we’ve got a great opportunity there, because one of the things that we found is that the tumors that reside in the lungs are hypoxic. They lack oxygen at the molecular level. That’s consequential because you need oxygen present at the molecular level in order for radiation to be effective and work. A lot of these tumors are non-responsive to radiation therapy – in fact, a lot of lung cancer patients are being unfortunately irradiated, and obviously science is on to it, we understand it. There’s a vital clinical need to oxygenate these tumors to enable therapy or sensitivity of these tumors to radiation.
The reason oxygen is important at the molecular level is because you need oxygen to facilitate transport of the electron beam to the nucleus of the cell to cut the DNA. If that electron beam hits that cell and there’s no oxygen, it just passes right through the cell. What it does is it inevitably arcs the cell which is on the margin of the tumor, which is typically the healthy autologous cell, and then it kills that and then that affects the immune suppression that has taken place around that in order to contain it.
So, effectively, you’ve got all of the soldiers, and the immune response around that tumor trying to contain it. You kill them, the tumor just grows. It’s been a problem and we’ve seen a bunch of patients that have been, unfortunately, over-radiated. The industry and science is better understanding what’s happening at the molecular level, personalized medicine is on the horizon, intelligence has gotten much better, and we’ve got our arms around what’s required.
MassDevice: What pathway will you follow through the FDA – 510(k), 510(k) de novo, straight 510(k), PMA?
LG: We’re going straight 510(k) on almost all the technologies. We believe the drug delivery has a 510(k) opportunity as well and we’re going to pursue that. We want to do the right thing, but at the same time, there’s an urgent humanitarian need, we’re got to get these technologies into the hands of the physicians who can use them and into the patients who desperately need them.
MassDevice: Is an HDE a possibility for the drug delivery platform?
LG: You mean a humanitarian device exemption? Absolutely. In fact, it’s a very perceptive point, something that we’re very tuned into. As it relates to the drugs, these drugs that we’re using are all FDA-approved. A lot of the drugs have been FDA approved for quite some time and they are assets that were acquired from the biological and chemical warfare assets of our military and others. But they came to find later that they’re either too cardiotoxic or too cytotoxic to be delivered systemically in the appropriate dosages to kill the tumor.
So while you might have killed the tumor, you killed the patient in the process, and that doesn’t to anybody any good. So consequently, these products were put on the shelf and they were there when they fell off patent. With the 12 drug-delivery patents that we’ve got, we’re actually taking about 35 of these drugs and putting them back on patent and we’re getting ready to take them off the shelf. That allows us to create what are called "new molecular entities" and makes us really a triple threat. We’re a diagnostic and a device and a drug, and you just don’t find that.
One of the things that’s happening is, given the impact of the cost burden of pulmonary diseases and chronic disease on the GDP and the economy, Congress has a number of lung cancer initiatives. One of the great things that’s happened is the seminal research that was sponsored by the [National Institutes of Health] and the NDI started in 2002, a national lung screening trial. It had 53,000 patients and 33 medical centers across the country. It’s a big study. And it did a comparative effectiveness study between chest X-ray and chest CT.
What they found was that the chest CT arm had a 24.2 percent increased detection of pulmonary anomaly, versus the chest X-ray group, which only had a 6 percent detection rate. It was clearly a statistically significant difference. However, on October 20, 2010, the NIH called off the study for humanitarian reasons because the chest X-ray branch of the study had a recognizable 20.3 percent increase in mortality. They were losing about 1 in 5 patients. They wanted to get those patients over to the CT group.
What that means is, we now have a new method of early detection, analogous to mammography for breast cancer, prostate examinations, colo-rectal examinations, where we’ve seen a discernible reduction in mortality, improving survival in those three cancers because of two things: Early detection, early intervention. Lung cancer has been long-neglected because it was obviously a disease of shame. We know that’s no longer the case, there’s a huge disparity of women who get lung cancer, who never smoke (17 percent) versus men who get lung cancer who never smoke (6 percent). It’s a huge disparity. In Japan the spread is 46 percent. One in eight Chinese men die from lung cancer. It’s the biggest killer of Chinese men. It’s huge.
So Congress is on it with the Lung Cancer Mortality Reduction Act and they’re trying to do what they can to reduce the cost burden of this disease to the GDP, because when you look at the cost burden of disease on the GDP, on the country, it’s $1.1 trillion. But when you look at a subset, such as pulmonary, you’re accounting for 15 percent of that metric. You’ve got to do something about that.
The national screening trial is a beacon of new opportunity for early detection. But while we’ve not achieved a new standard of care for early detection and any time a person presents with a pulmonary complaint they’re going to get a CT, they’re still lacking in intervention, and that’s what we’re after, that’s where we fit in.
We’re going to bring in the tools that are needed for these guys to do the diagnostic bronchoscopy, out to the periphery, to get a good cell culture so they can get a good immunology for personalized medicine and the right [epidermal growth factor receptor] and other immune therapies to remove the obstructive disease, to deliver drugs locally to beat the cancer back locally at inception.
MassDevice: And this is all sort of during one procedure?
LG: Yes. Per [the Centers for Medicare & Medicaid Services], the current length of stay for an endobronchial neoplasm is 7.7 days, which is longer than for open heart surgery. It’s our intention and our inspiration to get these patients out of the hospital in 24 hours. We’re fairly confident we’re going to be able to do it, because we de-risked the procedure. It’s going to improve the reimbursement equation, it’s going to reduce the cost on the system, it’s going to reduce the burden. There’s great value in regard to that.
MassDevice: What’s the reimbursement landscape for this treatment?
LG: It’s very healthy in the U.S. and it’s very healthy internationally.
MassDevice: Do you have your eye on emerging markets? Any of the BRIC countries, for example?
LG: The first thing we’ve done is build the foundational construct to build those markets. We’ve made sure that we’ve got our patents secured, not just the world patent. We’ve got about 25-plus pending with specificity to Europe, to India, to China, to Japan and obviously we’ve got world patents. But the most important thing is to make sure we’ve got our intellectual properties secured in the countries and domains.
Especially, in particular, in a country like India with a billion people and about 400 million in the middle class, you’ve got China with 4 billion and 250 million in the middle class. There’s definitely huge opportunity.
Plus, these are emerging nations and pulmonary disease is a chronic and endemic problem in the U.S. – 47 million people with pulmonary disease currently, 96 million at risk. One in seven people with a chronic obstructive disease in the lungs. That’s just in the U.S.