Kona Medical, Inc. is pioneering the use of focused ultrasound (FUS) to noninvasively treat hypertension through ablation of the renal nerves. Renal nerves are located near the renal arteries supplying blood to the kidneys and can play a significant role in regulating blood pressure. Recent clinical data have shown that ablation of renal nerves can result in profound and lasting reduction in hypertension in patients whose blood pressure is not adequately controlled by medication.
Founded in 2010, Kona Medical is headquartered near Seattle, is privately held, and has raised more than $60 million to date, including a recent $10 million to take their technology to China.
Q&A with Kona Medical Founder and CEO, Michael Gertner, MD
Q. How did you get involved in starting Kona? What is the unmet medical need in hypertension and why renal denervation? Why ultrasound?
A. My last company was a noninvasive radiation treatment for macular degeneration. When I finished there, I went to a cardiology meeting where catheter-based renal denervation was presented for the first time. I knew that the nerves could be treated from outside, and potentially this was a better way to treat the nerves given their variable location. However, radiation wasn’t the way to do this because nerves are difficult to ablate with ionizing energy, requiring high doses of radiation with precise targeting. The only other really penetrative energy is ultrasound. As a surgeon, I looked at renal arteries many times through the patient’s back. I figured we’d target the renal artery Doppler signal (not necessarily the nerves), and this is how we could do it noninvasively. Luckily, some venture capitalists also believed that this could be done. The unmet clinical need is hypertension. Despite many proven medications, more than 60% of patients continue to have uncontrolled blood pressures, leading to substantial morbidity and mortality. Current technology for renal nerve ablation requires a catheter procedure, which is expensive and subjects the patient and cardiologist to radiation. These technologies are also not suitable for repeat treatments.
Q. In general, what is the current status of your company?
A. We have raised $65 million in the last 3.5 years, of which $50 million has been closed in the past 12 months. We have treated 48 patients now with excellent results. However, we’ve been using a catheter inside the blood vessel to assist with targeting and tracking even though all the therapeutic energy is delivered from outside the patient. We are now treating patients using Doppler guidance and ultrasound imaging for targeting and tracking of the blood vessels. Our next major milestone will be a 50-patient study with ultrasound tracking and targeting conducted completely outside the catheterization laboratory and without any puncture of the skin. Beyond this, we need to develop a commercially acceptable embodiment of the system and work with the U.S. Food and Drug Administration to begin U.S. trials.
Q. How many years has your Surround Sound® Renal Denervation System been in development, and what are its origins?
A. The idea is four years old. I started out thinking about this in terms of MR-guided FUS, but for a number of reasons realized that this wasn’t a viable concept. Investors said “go with ultrasound imaging or go home.” Then, a stroke of luck: a company called Therus was essentially going out of business and had spent more than $40 million developing a technology to use FUS to close femoral blood vessels after angiography. I acquired the company and the technology and then hired the principles from the company to get Kona started. We also contracted with a company called Verasonics, which has a platform that allows for rapid experimentation with ultrasound. The path to noninvasive has been staged. As mentioned, we used a targeting catheter at first to segue to the completely noninvasive treatment.
Q. What are some of the technical challenges your group has to overcome to develop a fully noninvasive system?
A. The biggest challenges have been: 1) to get the therapy transducer to fit in the window behind the patient with an acceptable range of energy spread across to protect the skin; and 2) imaging the renal arteries and tracking respiration using ultrasound within this therapeutic window. Down the road, the challenge will be consolidating the system into a commercially viable embodiment.
Q. What other challenges will you have to tackle moving forward?
A. Because FUS is not yet a well-accepted form of therapy, we will face several regulatory and adoption challenges. There are not a lot of FUS experts within the regulatory authorities, and so the staffs are cautious. Additionally, hypertension is traditionally a medically treated condition, and because this is a disruptive technology, there is not an existing community of user physicians that will readily understand or champion the treatment. We will need to identify the specialists – whether interventional radiologists, cardiologists, or others – who will be early adopters and help drive widespread adoption. From a payer perspective, we have an excellent value proposition in terms of safety, costs, and efficiency.
The best and only way to deal with these issues is to start early and provide irrefutable scientific and clinical rigor. This was one of the reasons to raise a lot of funds for this project. We’ll perform a sham-controlled study for our phase III. Using the catheter to understand the motion parameters is also helpful in this respect. We’ve also had a modeling program going with a professor at the University of Washington since before I officially started the company. We’ve got thousands of hours of run time now for this problem.
From the patient standpoint, the requirement for the treatment is that it takes only a few minutes to set up and a few minutes to administer, which will be great marketing points. I also predict that we will be inherently safer than a catheter (which applies heat through the wall of the artery), and this will also help on the marketing side. In my experience, physicians will follow patient preferences (e.g., minimally invasive surgery). If the procedure is easy for physicians to learn, this will also drive adoption, and so this is one of our system requirements. Overall, our success will be tied to that of our invasive competitors. We need the market to expand. Medtronic just finished a pivotal study – we need that data to be positive to maintain enthusiasm for the market. If there is widespread interest in renal denervation, then we are confident that our technology will eventually capture a substantial share of the market and that there will be funding to support its commercialization.
Q. Tell us about your WAVE studies and the results.
A. The WAVE I and WAVE II clinical studies were conducted to evaluate and safety and efficacy of our Kona Surround Sound™ System using FUS on 24 WAVE I and 18 WAVE II patients in Australia, Canada, and the Czech Republic that were followed for at least 6 months and 3 months, respectively. The studies safely produced clinically significant drops in both systolic and diastolic blood pressure. (Read more about the studies.) These studies used a targeting catheter inside the renal artery—as mentioned in a previous question. From a development standpoint, we wanted to take the targeting and tracking challenges out of the equation and assure that we could in fact deliver the therapy safely and effectively through the window behind the patient. WAVE I and II accomplished this, and now we move to completely noninvasive ultrasound guidance in WAVE III to get to equivalent results.
Q. Is your noninvasive system ready for clinical trials? When will WAVE III start?
A. Yes, our fully noninvasive system is ready for trials. Without the catheter, we now use Doppler for targeting and tracking during the FUS treatment. The first 2 patients were treated noninvasively in WAVE III at the end of October. We’re going back to the Czech Republic in December and then to New Zealand in January and expect at least 25 patients treated by the end of the first quarter next year.
Q. Who are your competitors in renal denervation, and what are the benefits of your technology over other approaches?
A. Every major medtech company has done an acquisition or has an internal program, but as far as we know they are all catheter-based. We are differentiated and believe we will be the first choice for patients and clinicians. Our treatment has many benefits over alternative denervation approaches—it is noninvasive and can be done in the ambulatory setting with minimal anesthesia. In addition, without catheterization, there are no groin complications, no disposables, and the treatment is cheaper. Ultimately, FUS may be a better way to treat the nerves – you can retreat, and it is safer on blood vessels than catheter-based radiofrequency. From an anatomical standpoint, the nerves are located diffusely around the blood vessels, and there are likely technological challenges in the delivery of radiofrequency from inside the vessel. Kona, using its “Surround Sound” delivery, can treat a very large volume of tissue quickly. How large and how quickly will be the subject of our pre-clinical and clinical studies for years to come.