Benign prostatic hyperplasia (BPH), or enlargement of the prostate gland, affects about half of men between the age of 51 and 60 and up to 90% of men over the age of 80. Symptoms include difficulty with initiating urination, weak urine flow, post-void dribbling, and the need to wake up frequently during the night to urinate. Not only are these symptoms bothersome and negatively affect an individual’s quality of life, they may also lead to more serious conditions like bladder stones, urinary tract infections, or bladder and kidney damage. Unfortunately, many people with BPH choose to live with their symptoms due to the limitations and adverse effects associated with current treatment options. NxThera, an early-stage Minnesota-based medical device company, hopes to rectify these shortcomings and provide BPH patients with a new sense of hope with their FDA-cleared Rezūm system. The Rezūm system is a device that utilizes radiofrequency energy to create thermal energy in the form of water vapor to destroy and eliminate excessive prostatic tissue growth caused by BPH in order to resolve patient symptoms through a minimally invasive procedure with few-to-no side effects. We at Medgadget had the opportunity to sit down with Mr. Bob Paulson, President and CEO of NxThera, to ask him more about this exciting new technology.
Kenan Raddawi, MD, Medgadget: Can you please describe the Rezum Therapy System and the technology behind it?
Bob Paulson, CEO of NxThera: Rezūm uses thermal energy created with radio frequency power to very rapidly and efficiently ablate prostate tissue. The Rezūm system convectively delivers thermal energy to the prostate as compared to traditional heat ablation technologies that conducts thermal energy within tissue, and that conduction has certain limitations.
When water is phase-shifted from its liquid state to vapor state, it creates stored thermal energy in the form of steam, or vapor. In a nearly pure state of 93 to 94-percent vapor, the molecules are small enough to flow through the tissue interstices. As 105°C vapor is delivered into 37°C tissue, the water vapor phase shifts back to its liquid state, thereby releasing the stored thermal energy, and increasing the temperature of the tissue in the treated area to over 70°C, which causes instantaneous tissue cell death. Once cell death occurs, the body’s immune system comes in and cleans up the dead tissue. It’s a fundamentally different approach for transferring thermal energy in a very controlled and targeted fashion. The thermal energy doesn’t go anywhere other than where it is targeted to be delivered because vapor takes the shape of whatever container it is put in, and the prostate gland is anatomically compartmentalized.
Medgadget: It is my understanding that the Rezūm system was granted FDA clearance in August 2015. What kind of clinical trials did the Rezūm system go through to get FDA clearance? What current research supports the use of the Rezūm system?
Paulson: There were a series of studies that began with animal studies, progressed to studies of extirpated human prostate tissue – where patients were treated in vivo, and then, their prostates were removed and evaluated.
Once we validated the technology, we moved to a combined first-in-man/pilot study where 65 patients were treated with the Rezūm technology and evaluated through a combination of MRIs and patient-reported symptom relief using a series validated assessment instruments. As a part of these early studies, we worked with the Mayo Clinic Foundation Biomedical Imaging Resource Center to create three-dimensional volumetric renderings of these MRIs to assess the treatments and resorption of treated tissue at 1 week, 1, 3 and 6 months. This imaging data then was correlated to the patient outcomes data. The one and two year data from the Rezūm FIM and Rezūm I pilot study has been published and demonstrates the safety, efficacy and sustained outcomes from this study.
Collectively, the Rezūm FIM and Rezūm I pilot study data was used to support obtaining an investigational device exemption (IDE) from FDA to conduct the Rezūm II pivotal study that was done in the U.S., a 197-patient 2:1 randomized controlled study. The one-year safety and efficacy data from the Rezūm II pivotal study supported a 510(k) clearance by FDA and has been published. The net takeaway is that the one and two year outcomes and safety data demonstrated in both the Rezūm FIM & Rezūm I pilot study, and the Rezūm II pivotal study – all of which have been published in peer-reviewed articles – correlate almost dead-on demonstrating sustained improvement in symptom scores, urinary flow rates, quality of life, no change in sexual function – the means by which the severity of this condition are measured.
Medgadget: Has Rezūm been approved for use in other countries besides the U.S., and/or are there plans to try and get Rezūm approved in other countries?
Paulson: Yes, the Rezūm system received CE mark in 2013. While we were running the Rezūm II pivotal study, we worked on early commercial adoption at various accounts in Germany and a clinic in Stockholm, Sweden. However, as a venture-backed medical device company, we are forced to make choices on where we spend our capital, and we chose to limit our international business to these two markets at this time. Between 2013 and 2015, our priority was to obtain FDA clearance. In 2017, we expect to begin a staged expansion outside the U.S., moving more aggressively in Germany and expanding into the UK while we are concurrently expanding commercial adoption in the US.
Medgadget: What advantage does Rezūm have over other available treatments like UroLift, Greenlight Laser PVP, or TURP? Basically, why should people choose Rezūm over other BPH treatment options?
Paulson: First let’s talk about what the other treatments are, and then, my answers will make sense. TURP and Greenlight are surgical procedures. One of the significant side effects of surgical procedures is a higher incidence of retrograde ejaculation. There is not much you can do to avoid this side effect simply because, anatomically, tissue is being resected or vaporized from the prostate which can impact the bladder neck, which affects ejaculation. So, preserving sexual function is a big consideration for a patient.
At the other end of the scale, there are two primary classes of drugs used to treat BPH. There are Alpha-blockers which selectively block Alpha-receptors in the hyperplastic stromal tissue of the prostate. These drug are taken systemically, which not only affects the Alpha-receptors in the prostate, but in every muscle in the body, including the heart. Aging men, who are highly affected by BPH, have a higher incidence of other advancing chronic conditions. If somebody is taking hypertension medications, like Beta-blockers, and an Alpha-blocker is added to their medication regime, they likely will feel lethargic and tired. The other class of drugs is 5-Alpha-reductase inhibitors, which reduce the production of testosterone. Again, in an aging male population, many men begin to experience erectile dysfunction (ED), and by reducing testosterone, a man’s ED may be exacerbated. Neither of these drugs treats the underlying condition – the hyperplastic tissue that obstructs the urethra. These drugs can mask the symptoms, but do not treat the underlying growth of hyperplastic tissue.
Surgical BPH procedures resect or vaporize prostate tissue, but side effects can include significant post-procedure discomfort, pain, bleeding and other complications. Plus, a patient will spend 45 to 90 minutes under general anesthesia during these procedures, and many physicians try to avoid general anesthesia in an aging population.
UroLift is an implant – an interesting concept. A series of implants mechanically pulls open the prostate. However, the implants do not treat the underling hyperplastic tissue, so the hyperplastic tissue will continue to grow over time. While the longer-term outcomes data appears to be declining somewhat over time, in some respects that is to be expected because the hyperplastic prostate tissue continues to grow. Because implants are permanent, in time, if the hyperplastic tissue growth continues, another procedure may be required to alleviate the obstruction. UroLift procedures often are done in the operating room, and for the most part, under general anesthesia or conscious sedation. So the typical anesthesia protocol often is comparable to a more invasive surgical procedure.
So, what has been missing? An efficient, office-based, minimally invasive procedure that provides consistent sustained outcomes, with minimal complications or side effects. Earlier radiofrequency and microwave ablation therapies were traditionally office-based procedures, but the clinical outcomes were not consistent or predictably durable. These ablation procedures imparted significant amounts of electromagnetic energy to the tissue, were 30- to 45-minute procedures, and patients often experienced extended post-procedure discomfort. They didn’t fit well into the standard clinical office algorithm, and the post-procedure pain and discomfort led to very narrow adoption.
In contrast, the Rezūm system is a very efficient procedure, a series of 9-second injections of convective RF thermal energy, which typically are delivered only under a prostate block as anesthetic. With an effective prostate block, patients tolerate the procedure very well. The Rezūm II pivotal study demonstrated that physicians can choose a variety of anesthetics that fit patient needs or a physician’s practice – a prostate block, anti-anxiety and pain medications, or conscious sedation, whatever works best in the physician’s judgment. The Rezūm procedure is efficient and will fit into a physician’s normal clinic office algorithm. In addition, the published clinical data has demonstrated sustained clinical outcomes at one and two years are comparable to that reported for surgical procedures, but done in a very efficient and cost-effective office-based procedure.
Medgadget: From your perspective as a CEO, what do you think the future holds for this technology? Do you see it being utilized to treat other types of medical conditions (i.e., prostate cancer), etc.?
Paulson: There is no question. Convective RF thermotherapy is a platform technology – NxThera is licensed to use this technology for urological applications. There are other companies who have a license to the underlying intellectual property to use for other indications. At NxThera, we are focused on just urology. The beauty of this technology is that you can do zonal ablation, regional ablation, hemi ablations (e.g., ablate half the prostate), whole gland ablations, or just a spot (e.g., focal ablation). We are working on creating an ablation tool for the physician to decide how best to treat prostate cancer. Where today the options for patients with prostate cancer are all “sledgehammers” – the whole prostate is radiated, treated with cryoablation, high intensity focused ultrasound (HIFU), or removed – each with a very high incidence of ED and/or incontinence which affects men for the rest of their lives.
Medgadget: What is the training process for physicians who would like to offer Rezūm to their patients?
Paulson: Interested urologists either contact us, or we will contact them within their practices. We take urologists through a series of discussions to review the clinical data and help them understand the convective RF water vapor thermal ablation technology. We also have invested in procedure simulators which allow physicians to learn the procedures by performing a series of simulated cases.
The cases are very realistic as the baseline cases were developed using procedure videos from 197 different patients in the Rezūm II pivotal study. We developed five very representative procedures from easy to most challenging – “most challenging” is primarily related to differences in anatomy. The simulator software allows the physicians to see exactly what is happening during the procedure. Not only do they have the direct visualization of the procedure as they will see it during an actual case, but the simulator software also allows them to visualize the effect of the tissue ablation occurring within the prostate. The simulator scores how effectively the physicians perform the procedure, and a physician must score 85 percent or higher on each of the five cases before they can go on and perform their initial patient case(s). A NxThera clinical representative attends a physician’s first ten cases to assist and guide staff and the physician, as needed. Once a physician successfully completes their initial 10 case training regime, we sign off, and the urologist can perform future Rezūm procedures independently.
Medgadget: How much does Rezum cost? How expensive is this technology for physicians to use in the clinic, and how does the cost of Rezūm compare to other minimally invasive BPH treatments options?
Paulson: The AUA has advised urologists to use an existing CPT code 53852 – transurethral destruction of prostate tissue; by radiofrequency thermal therapy. The national average Medicare reimbursement for CPT 53852 is approximately $1,950 when performed in the office. That means after paying for the device and whatever supplies the physician uses during the procedure, the net difference is what the physician makes on each procedure. The list price of the delivery device, which is single use, is $1,400 per device. The average selling price is just over $1,150. So if a physician pays $1,150 for the device and receives $1,950 for the procedure, they will receive $800 per procedure, less any other costs and overhead.
RF thermotherapy to treat BPH has been around since the mid-nineties – it is considered medically necessary and covered by most insurance companies. Because transurethral needle ablation (TUNA) procedures are covered procedure under most health insurance polices, patients are required only to pay whatever their deductible is for their covered policy.
Now, let’s talk about the cost to the health care system. The average reimbursement for a TURP or laser treatment, which includes both a facility fee, because it has to be done in the hospital, and a physician fee, the all-in cost is around $3,500 to $4,500 to the healthcare system. If you talk about the UroLift implants, they will receive an increased reimbursement in 2017, and the average cost to the healthcare system is over $7,000.
So, Rezūm is on the “right side” of the health care equation. The reason we believe payers will look favorably upon Rezūm is that we now have two-year clinical efficacy and safety data which demonstrate outcomes comparable to BPH surgical procedures, with a cost to the healthcare system of somewhere between $2,500 and $3,000 less than the other more aggressive or permanent implant options.
Medgadget: What can patients expect during and after the procedure? What adverse effects may patients experience after a Rezūm treatment?
Paulson: During a Rezūm system procedure physicians have options as to what anesthetic they use. The majority of practices today use a modified prostate block, the same type of local anesthetic procedure typically used for trans-rectal biopsies. With an effective prostate block, patients tolerate the procedure very well and do not feel much of anything during the procedure. Many physicians send patients home with a catheter for 48 – 72-hours post-procedure to allow tissue inflammation from the ablative therapy to moderate. Again, this is the physician’s choice.
During the Rezūm II pivotal study, the reported adverse events were of the type typically observed with any transurethral procedure with a rigid scope. First, 60% of the patients did not report any adverse events, and those adverse events that were reported typically were mild-to-moderate in severity and resolved within 3 weeks. The most common adverse events included discomfort urinating, frequency of urination, urgency to urinate, or blood in the urine or semen.
Here’s a video introducing the technology followed by an actual example procedure:
Product page: Rezūm…