The FDA has given Medtronic plc the go-ahead to conduct an early feasibility study of its Intrepid transcatheter mitral valve replacement (TMVR) system using a minimally invasive transfemoral transseptal approach. The new study builds upon primary endpoint outcomes seen in the company's APOLLO trial to assess Intrepid in patients with severe, symptomatic mitral valve regurgitation (MR) using the transapical approach.
MR affects about 4 million Americans, making it the most common form of heart valve disease. The standard treatment for MR is medical management or open heart surgery to replace or repair the leaky mitral valve, but both have safety and durability issues and many patients are forced to get by on medications that treat MR's symptoms but not the disease because they are not good candidates for the surgical option. Left untreated, MR can lead to chronic heart failure.
Under the protocol approved by the FDA, Medtronic will enroll up to 15 patients with severe, symptomatic MR who are ineligible for conventional mitral valve surgery and treat them using the Intrepid system via transfemoral placement. In this approach, the valve is delivered through a vein in the groin, rather than transapically, which requires an incision through the rib cage called a thoracotomy. The prospective, multicenter, nonrandomized study will assess the safety and performance of device and treatment approach with patient follow-up at one, three, six and 12 months and then every six months through five years. Results from this early feasibility study will help to inform refinements in the next generation of transfemoral TMVR systems, the Dublin-based company said.
The Intrepid TMVR system employs self-expanding, dual-stent technology and a tissue valve, which is delivered via a catheter and inserted into the patient's own mitral valve to restore normal blood flow without having to open up the chest cavity. In the Intrepid TMVR APOLLO study using the transapical point of insertion, 48 of 50 patients were successfully treated with the device. Thirty-day mortality was 14%, with no disabling strokes or repeat interventions. The findings were published in the Jan. 2-9, 2018, issue of the Journal of the American College of Cardiology.
"Medtronic believes that transcatheter mitral valve replacement will have a vital role in treating patients with mitral valve disease and this early feasibility study is another step forward in our Intrepid program," said Nina Goodheart, vice president and general manager of the structural heart business in Medtronic's cardiac and vascular group.
Martin Leon, director of the Center for Interventional Vascular Therapy at New York-Presbyterian/Columbia University Medical Center and professor of medicine at the Columbia University College of Physicians and Surgeons, expressed his optimism about the transfemoral approach. "The early clinical results we have seen with Intrepid and this early feasibility study advances the TMVR field as we look for less invasive ways to treat this patient population, of which a large proportion are considered too high risk for surgery."
Currently, the Intrepid system is not approved for commercial use in any country. Medtronic spokeswoman Wendy Dougherty told BioWorld MedTech that the company is working with regulatory bodies on the regulatory and clinical paths for its investigational TMVR technologies, but declined to specify a timeline for regulatory approvals. The company estimates the market potential for MTVR to be in the $5 billion range.
Plenty of competition
Medtronic is not the only company pursuing TMVR therapies. Abbott Laboratories' Mitraclip remains the only FDA-approved minimally invasive mitral valve repair device. In July 2018, the company reported the agency had approved its pivotal study for the Tendyne TMVR device, which aims to evaluate safety and performance in 1,100 patients with severe MR. The Abbott Park, Ill.-based company is also assessing Tendyne's use in 100 patients with severe mitral calcification. And in a further sign that it intends to be a major contender in the TMVR space, Abbott earlier this year snapped up Cephea Valve Technologies Inc., of Santa Clara, Calif. (See BioWorld MedTech, Jan. 17, 2019.)
Paris-based Highlife SAS closed a €32 million (US$36.4 million) equity financing round in January to back its TMVR system. The proceeds were earmarked for completion of the system's development, which includes regulatory approval trials in Europe and an early feasibility study in the U.S. (See BioWorld MedTech, Jan. 22, 2019.)
Other competitors include Livanova plc, of London, whose Caisson TMVR device is being assessed in pivotal trials in the U.S. and EU, and Edwards Lifesciences Corp., of Irvine Calif., which last week released positive one-year data from the early CLASP study of its Pascal transcatheter valve repair system. (See BioWorld MedTech, Sept. 27, 2019.)
Evolut PRO+ fully launched
Meanwhile, Medtronic has fully launched its Evolut PRO+ transcatheter aortic valve replacement (TAVR) system, following FDA approval last week. The device is now indicated for the treatment of symptomatic severe aortic stenosis patients across all risk categories.
"Medtronic is committed to providing the tools for physicians to fine tune TAVR procedures," Dougherty said. "As TAVR is available now for patients at the lower end of the risk spectrum, and with a wider variety of anatomies, certain features in a valve become more important – like hemodynamics, valve size options, design to help reduce [paravalvular leak]."
In a Friday research note, Joshua Jennings, of Cowen Equity, said Medtronic "reprised its excitement about the PRO+ launch and future TAVR markets like asymptomatic AS patients" during an update at the Transcatheter Cardiovascular Therapeutics conference in San Francisco. The company estimates that the new indication and growing awareness of TAVR's benefits in low-risk patients could spur up to 200 new TAVR centers in the U.S., up from about 600 existing centers.