FDA Advisory Panel Unanimously Rejects Johnson & Johnson's V-Wave Heart Shunt for Heart Failure
核心洞察
The FDA's Circulatory System Devices Panel voted 0-15 against approving Johnson & Johnson's V-Wave Ventura interatrial shunt for heart failure patients with reduced ejection fraction.
The panel concluded there was insufficient evidence of effectiveness, as the RELIEVE-HF trial failed to meet its primary endpoint despite showing some safety in periprocedural outcomes.
While 9 of 15 panelists considered the device safe, all 15 voted that effectiveness was not proven, citing concerns about long-term efficacy and potential harm in certain patient subgroups.
An FDA advisory panel delivered a unanimous rejection of Johnson & Johnson's V-Wave Ventura interatrial shunt system, voting 0-15 against recommending approval for treating heart failure patients with reduced ejection fraction who remain symptomatic despite guideline-directed medical therapy.
The FDA's Circulatory System Devices Panel determined that the risks from the interatrial shunt system outweighed the benefits in patients with NYHA class III heart failure with left ventricular ejection fraction of 40% or less. All 15 panelists voted that the device's effectiveness was not proven, while the safety vote was split with nine panelists supporting safety and six opposing.
Trial Results Drive Rejection
The panel's decision was based primarily on results from the RELIEVE-HF trial, a double-blind, randomized placebo-procedure-controlled study presented at the 2024 American College of Cardiology Scientific Session. While the implant showed some reduction in heart failure hospitalization risk for patients with heart failure with reduced ejection fraction versus placebo, it was associated with a more than threefold increased risk for all-cause mortality in patients with heart failure with preserved ejection fraction.
"Everything was driven by the absence of overwhelming evidence of benefit, and given the number of other opportunities to change the natural history of heart failure and all its various phenotypes, the evidence bar is high," said Clyde W. Yancy, MD, professor and chief of cardiology at Northwestern University Feinberg School of Medicine. "This is not an end of this discovery... There may be benefit, and if we continue to work diligently like we have in heart failure for decades, we may be able to answer this question with more precision."
Device Technology and Safety Profile
The V-Wave Ventura system is implanted via a 14 French delivery system, creating a small orifice in the fossa ovalis. In the left atrium, expanded polytetrafluoroethylene channels blood flow into the right atrium while preventing lumen loss. The device is designed as a permanent implant to shunt blood from the left to the right atrium, reducing elevated left atrial pressure in patients with advanced chronic heart failure.
In the RELIEVE-HF trial, there were no reported device- or procedure-related adverse cardiovascular events at 30 days or 2 years. However, panelists expressed concerns about long-term effects and potential harm to certain patient populations.
Primary Endpoint Concerns
Panel members emphasized their adherence to the trial's primary endpoint, which was not met in the study. "We didn't meet the primary endpoint, and therefore the rest is hypothesis generating," said Richard Page, dean of the Larner College of Medicine at the University of Vermont. "We don't want to give false hope, and we don't want to believe that we're addressing a problem if we really don't have data to support that."
Paul J. Hauptman, MD, dean and professor at University of Nevada, Reno School of Medicine, noted his struggle with safety concerns: "Like some others, I struggled with safety more than efficacy. Periprocedurally, this appears to be a safe procedure. I do have concerns about the long-term effects with regards to efficacy."
Regulatory Status and Next Steps
Johnson & Johnson acquired V-Wave Ltd (搜索). in 2024, bringing the interatrial shunt technology into its portfolio. The device received FDA breakthrough device designation in 2019 for its potential to address unmet needs in improving prognosis for patients at significant risk for hospitalization and death. The shunt has received CE mark approval and is approved for marketing in the European Union but remains unapproved for commercial use in the United States.
Following the panel vote, a Johnson & Johnson spokesperson stated the company is reviewing the FDA advisory panel's recommendation for additional clinical evidence. "We will continue to work closely with the FDA, clinicians and other stakeholders to determine next steps," the spokesperson said.
FDA staff noted in their briefing that "statistical testing of subgroups beyond an interaction test of the primary endpoints may be considered hypothesis-generating and should be interpreted with caution." While the FDA is not required to follow advisory committee recommendations, it typically does so in making final approval decisions.