FDA Issues Not-Approvable Letter for enVVeno’s VenoValve for CVI

August 20, 2025—enVVeno Medical Corporation announced that it has received a not-approvable letter from the FDA in response to its premarket approval (PMA) application for VenoValve, a surgical replacement venous valve for treating severe deep chronic venous insufficiency (CVI).

According to the company, the letter indicates that the FDA completed its review of the application and determined that it is unable to approve the PMA for the VenoValve in its current form.

enVVeno advised that in particular, the FDA indicated that the favorable revised Venous Clinical Severity Score data generated by the SAVVE United States pivotal trial of the device to show clinical improvement—together with the improvements in pain scores and venous-specific quality-of-life indicators—was not sufficient on its own to determine favorability of the benefit-risk profile for the VenoValve. Without a specific hemodynamic measurement that correlates with patient improvement, the FDA raised concerns about bias and the possibility that clinical improvement occurred as a result of the patients being enrolled in a study.

The FDA also focused on safety concerns attributed to the VenoValve open surgical procedure that required rehospitalizations. The company would not expect to see similar safety events with a nonsurgical replacement valve, noted the press release.

“We are obviously disappointed by the FDA’s decision,” stated Robert Berman, Chief Executive Officer of eVVeno Medical, in the company’s press release. “The results showed that a high percentage of the patients in the SAVVE study, who all previously failed standard-of-care treatments, showed significant clinical improvement after receiving the VenoValve. With the VenoValve being the only difference in their care, it is hard to not attribute the improvement to the VenoValve.”

Berman continued, “We remain committed to the 2.5 to 3.5 million patients suffering from severe deep venous CVI in the United States and who have no effective treatment options and will continue to work with the FDA on new criteria to demonstrate the safety and effectiveness of our devices.”

Also in the press release, enVVeno Medical stated that it is reviewing the feedback from the FDA and is assessing all options, which may include a meeting to discuss requirements for a potential resubmission of the VenoValve or appeal of the decision along with appropriate next steps. The company also expects to apply the key learnings from this FDA approval process as it advances enVVe, its nonsurgical replacement venous valve for which it is preparing an investigational device exemption application.

In November 2024, enVVeno announced that 1-year data on all patients from SAVVE were presented at the 51st annual VEITHsymposium. In April 2025, the company announced the presentation of findings from a subanalysis of the 1-year SAVVE data at the 52nd annual symposium of the Society for Clinical Vascular Surgery.