NATIONAL HARBOR, Md. – Cardiovalve Ltd., of Or Yehuda, Israel, scored a double hit with the U.S. FDA, winning a breakthrough device designation for its transcatheter tricuspid valve replacement system, as well as approval to conduct an early feasibility study in tricuspid regurgitation (TR). The tricuspid application builds on Cardiovalve’s ongoing studies in mitral regurgitation (MR) patients.

Clinical sites for the TR study are being activated, and “recruitment will start in Q2 2020,” founder and CEO Amir Gross told BioWorld.

TR is a condition where the valve between the two right chambers of the heart don’t close properly, allowing blood to flow back into the heart’s upper right chamber, or atrium. The leaky valve can cause patients to feel fatigued and short of breath, and can lead to heart failure and atrial fibrillation. An estimated 1.6 million Americans have TR, yet only about 8,000 a year have surgery to treat the condition.

Three valve sizes

The Cardiovalve system is designed to be a transfemoral venous access system with a transseptal approach, and is intended to replace the mitral or tricuspid valve via a minimally invasive procedure. The company has three valve sizes (M, L and XL), which cover about 90% of prospective patients.

“Cardiovalve is a truly percutaneous transfemoral system with a valve that fits almost all annuli sizes … with very limited anatomical restraints,” Gross said. The company plans to add an XXL size in the next year.

The prospective, multicenter, single-arm study will evaluate the safety and feasibility of the device and procedure in reducing TR, with evaluations at 30 days and periodically up to five years. in 15 patients at up to five clinical sites in the U.S. The target population is patients with moderate to sever TR requiring tricuspid valve replacement who are at a high risk for open chest surgery. A total of 15 patients will be enrolled at up to five centers in the U.S., with enrollment to last up to one year.

“I am excited to finally have a truly percutaneous approach for treating TR,” said Azeem Latib, medical director of structural heart interventions at Montefiore Medical Center in New York City, and principal investigator for the U.S. TR study. “The Cardiovalve system is an innovative solution for an unmet clinical need.”

Cardiovalve is currently testing the feasibility of its system in treating mitral regurgitation in the AHEAD studies in the U.S. and Europe. Both are prospective, multicenter, single-arm studies targeting symptomatic, New York Heart Association (NYHA) Class II-IV patients with severe MR requiring valve replacement who are at risk for open chest surgery. The U.S. study is enrolling a total of 15 patients at five clinical sites. Its European counterpart will enroll a total of 30 patients at up to 20 sites in Germany, Switzerland and Italy.

Early results for AHEAD EU pilot

During a session on recent pilot studies at CRT20 on Feb. 23, Latib shared results from the first five patients treated in the EU study.

All of the patients were symptomatic, NYHA Class III with ischemic MR. in addition, all had severe MR with an average effective regurgitant orifice area (EROA) of .6, average left ventricular end-diastolic distention (LVEDD) of 61, systolic pulmonary arterial pressure (sPAP) of 52 and an ejection fraction of 33%. The entry criteria was an ejection fraction of 30%.

Investigators successfully implanted the valve in all five patients. “The results were really good,” Latib said. “The valve did what it was supposed to do, got rid of MR. So in 80% of the patients, no MR. One patient had mild MR.”

The positive outcome was marred, however, by three patient deaths at 30 days. While none was device-related, they pointed to procedural issues with exit site bleeding and deep vein thrombosis.

“The biggest challenge yet wasn’t really getting the valve to the right place and implanting the valve in the right place, it was how do you manage these patients’ exit sites,” Latib said.

The results raise questions such as “should we be using surgical access in these procedures? Would that be better than percutaneous access through the femoral vein? But also how do we manage … these very sick, frail patients who … can’t tolerate a complication,” he said.

As Cardiovalve launches in-human studies in tricuspid regurgitation, it will benefit from the breakthrough designation, which comes with extra communication from FDA and expedited review and reimbursement processes.

“We now have clinical data two years out that our implant is functioning as expected and the patient is improved clinically,” said Amir Gross, Cardiovalve’s founder and CEO. “FDA’s ‘breakthrough’ designation validates and reaffirms our commitment to improving and extending the lives of millions of patients suffering from heart valve disease across the world.”

He declined to discuss possible regulatory pathways and timelines for the MR and TR indications.

Competition

Spun out of Valtech Cardio Ltd. when the latter was acquired by Edwards Lifesciences Corp. in 2016, which Gross also founded, privately held Cardiovalve has a 27,000-square-foot ISO-certified R&D and manufacturing center in Israel, with 40 full-time employees. Gross said the company’s investors include large venture capital firms, but did not provide details except to say a new financing is being planned for this year.

As it advances its mitral and tricuspid programs, Cardiovalve faces competition from weighty contenders like Edwards, Abbott Laboratories and Medtronic plc. Edwards’ Pascal transcatheter valve repair system received CE mark approval to treat MR in February 2019. A trio of U.S. pivotal trials for Pascal are continuing to enroll. Edwards also has the Cardioband MR system, but has postponed starting a pivotal trial until a next-generation version is ready.

Meanwhile, Abbott’s investigational Triclip device for TR patients has been shown to be safe and associated with strong clinical improvement at six months. Last fall, the company also reported new data demonstrating the cost-effectiveness of Mitraclip vs. guideline-directed medical therapy alone in heart failure patients with secondary MR. Abbott also has the Portico self-expanding transcatheter aortic valve replacement system, which has been shown to be noninferior to Edwards’ Sapien and Medtronic’s Corevalve in extreme or high-risk aortic stenosis patients at one year.

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