FDA Approves Edwards Lifesciences’ SAPIEN M3 as First Transseptal Transcatheter Mitral Valve Replacement Therapy

Edwards Lifesciences has received U.S. Food and Drug Administration (FDA) approval for its SAPIEN M3 mitral valve replacement system, making it the first transcatheter therapy using a transseptal approach to be cleared for the treatment of mitral regurgitation. The system is indicated for patients with symptomatic moderate-to-severe or severe mitral regurgitation who are considered unsuitable for surgery or transcatheter edge-to-edge repair by a multidisciplinary heart team. The approval also covers certain patients with mitral valve dysfunction associated with mitral annular calcification.

Mitral regurgitation is among the most common forms of valvular heart disease, and many patients remain untreated due to limited therapeutic options. David Daniels, M.D., a cardiologist at Sutter West Bay Medical Group, said, “Up to this point, many patients were unsuitable for available treatment options, leaving the vast majority untreated and suffering.” He added that the SAPIEN M3 system offers a fully percutaneous approach that can substantially reduce regurgitation and improve symptoms in a population with few alternatives.

The SAPIEN M3 procedure is performed in two stages, beginning with the delivery of a docking system and followed by the implantation of the replacement valve. Both components are delivered through a steerable guide sheath inserted via the femoral vein, allowing for complete mitral valve replacement without open-heart surgery.

Clinical evidence supporting the approval comes from the ENCIRCLE single-arm pivotal trial, with one-year data presented at TCT in October 2025 and published in The Lancet. In the main study cohort of 299 patients deemed unsuitable for other therapies, the trial met all primary and secondary safety and effectiveness endpoints. Investigators reported that 95.7 percent of patients achieved near-complete elimination of significant mitral regurgitation, alongside meaningful improvements in symptoms and quality of life.

The SAPIEN M3 system received CE Mark approval in April 2025, becoming the first transfemoral transcatheter mitral valve replacement (TMVR) system approved in Europe. Daveen Chopra, corporate vice president for transcatheter mitral and tricuspid therapies at Edwards, said the approval expands the company’s ability to address unmet needs in structural heart disease and complements its existing portfolio of FDA-approved mitral and tricuspid repair and replacement therapies.