Hypertension is a ubiquitous problem that many companies – both pharma and device – are looking to address. Now, a privately held Mountain View, Calif.-based company, Vascular Dynamics Inc., is looking to offer a new minimally invasive option that can help patients who are resistant to drug therapies.
The company this week reported that the CALM-2 (Controlling and lowering blood pressure with Mobiushd) study, which is designed to establish safety and efficacy of the novel endovascular baroreceptor amplification procedure using the Mobiushd device, has begun initial enrollment. It is estimated that more than 100 million people in the U.S. have hypertension. However, more than half of those treated with antihypertensive medications continue to have uncontrolled high blood pressure.
For its part, Vascular Dynamics is concentrating on baroreceptors, which are nerves located in the carotid artery that can detect changes in stretch of the arterial wall and signal the brain to control blood pressure. Mobiushd aims to use this natural blood pressure control system to address uncontrolled hypertension.
This prospective, randomized, sham-controlled, double-blinded CALM-2 pivotal trial will enroll about 300 patients with resistant hypertension who are on up to five medications. Patients will be followed for five years, returning for five follow-up visits over the first year, and then two visits per year over the next four years. The first patients were enrolled at the Center for Clinical Research at Southern Illinois University Medicine and The Lindner Research Center at The Christ Hospital Health Network.
"Enrolling the first patients in the CALM-2 trial is an important step toward offering a new treatment option for this large patient population with resistant hypertension and the associated health risks," said Gregg Stone, co-principal investigator of the CALM-2 trial and director of cardiovascular research and education for New York-Presbyterian/Columbia University Medical Center and co-director of medical research and education at the Cardiovascular Research Foundation.
Stone has had extensive experience with hypertension. "I've recently been involved [with] new device therapies for hypertension, starting with early renal denervation and now with the Mobiushd device," Stone told BioWorld MedTech. "It's actually implanted very similarly to a carotid stent," Stone said when asked about the procedure itself, which is performed under X-ray visualization. "It's done in a cardiac catheterization laboratory. There is a small amount of local anesthesia given in the groin over the femoral artery, and then a catheter is passed from the femoral artery up into the neck in the carotid artery," he added. Once in place in the internal carotid artery, a restraining sheath is retracted, allowing the nitinol-based implant to pop out. It is then held in place by outward forces. The catheter is subsequently removed, ending the approximately 30-minute procedure. Stone noted that the whole process is "essentially painless" and poses a low risk.
"It's very different from renal denervation, of course," Stone said when asked about other procedures. "Renal denervation is using either radiofrequency or ultrasound or alcohol ablation to denervate the renal nerves," he explained. While it is a relatively simple procedure, it is more complicated than delivering the Mobiushd. In addition, it can cause pain, particularly with the radiofrequency and ultrasound techniques.
Learning from the past
"There's been a lot of learning from the prior renal denervation experience," said Stone. "This saga has been going on for 10 years now." He noted that initial studies were unblinded and uncontrolled, and the results looked promising. However, when the large, sham-controlled study was performed, the results were negative.
"In retrospect, there were a lot of things that could have been or should have been done differently – [controlling] which patients got into the study, [standardizing] the technique, [minimizing] crossover in medications from one arm to the other – which might have led to a positive study," Stone explained.
With that said, Medtronic plc and Recor Medical Inc. have taken these lessons and conducted smaller pilot sham-controlled studies that yielded positive results. Still, the procedure appears to work best in those off-medication or with mild-to-moderate hypertension, but there is a great clinical need for those with a more severe form of the condition.
In terms of feedback for Mobiushd, Stone said the reduction in blood pressure seen with this technique has been impressive, "more so than we've seen with renal denervation," he added. For some patients, the reduction has been so marked, that they have had to back off on some of their hypertension medications.
Ed Roschak, the company's president and CEO, is looking to expand the company to execute on the CALM-2 trial. "We are putting the right team and processes in place to successfully complete this landmark trial and to develop compelling clinical evidence to support future FDA approval," he said. The company reported his hiring as CEO in December 2017.
There are other potential players looking to make a splash in helping those suffering from hypertension, including Israel-based Pythagoras Medical. Earlier this year, Pythagoras won the CE mark for its minimally invasive Confidenht system, which is intended for those whose hypertension is not controlled by medication, for renal denervation combined with real-time guidance for ablation, as well as confirmation of successful ablation. (See BioWorld MedTech, April 2, 2018.) Specifically, the system is designed to provide real-time guidance in finding hot spots to ablate in renal denervation procedures.
For its part, Medtronic, of Dublin, won FDA IDE approval for a pivotal study of its Symplicity Spyral renal denervation system in treatment of patients with hypertension earlier this year. (See BioWorld MedTech, April 10, 2018.) The trial, SPYRAL HTN, is being conducted as part of the multiphase Spyral HTN global clinical program evaluating its renal denervation platform. Symplicity Spyral has scored approval in 50 countries, but is an investigational device in Japan and the U.S.
Palo Alto, Calif.-based Recor has received a green light for a pivotal study, dubbed RADIANCE-II, evaluating the Paradise ultrasound denervation system for the treatment of hypertension. (See BioWorld MedTech, July 3, 2018.) The study aims to build on results from the RADIANCE-HTN SOLO trial and will assess patients with moderate hypertension as the company looks to make a submission to the FDA. In July, Recor reported that it was being bought by Otsuka Holdings, of Tokyo.
Another player is Rox Medical, of San Clemente, Calif. It has developed a coupler that is placed between the artery and vein in the upper thigh to allow a fixed amount of blood to flow between them. It is placed during the minimally invasive Rox Flow procedure. The company is sponsoring the Rox Medical CONTROL HTN-2 clinical trial, which is currently enrolling in the U.S. The coupler is commercially available in Europe under CE mark. Last month, the company reported the hiring of its new CEO, Mike MacKinnon.