- The Food and Drug Administration published a briefing document to inform the discussion at an advisory committee that will debate Abbott’s Triclip device on Tuesday.
- Abbott is seeking premarket approval in symptomatic, severe tricuspid regurgitation on the basis of a pivotal trial that met its primary endpoint but raised questions about the efficacy and safety of the device.
- In a report to investors, J.P. Morgan analysts noted the FDA’s queries on safety, but added the document is “generally supportive” of authorization given the proposed label and “simple voting questions” that “all lean towards approval.”
Abbott developed Triclip to enable surgeons to repair tricuspid valves that no longer close properly and therefore allow blood to leak back into the right atrium of the heart. Edwards Lifesciences won FDA approval for its transcatheter valve replacement device, Evoque, earlier this month.
J.P. Morgan analysts see “a place for both repair and replacement.”
On Tuesday, a panel of experts convened by the FDA will discuss whether the data on Triclip show it is a safe, effective option for valve repair. The briefing document identifies areas the agency wants expert input to inform its decision on whether to approve the device.
As the FDA notes, Abbott’s open-label Triluminate trial met its primary endpoint, a composite of components at 12 months, including all-cause mortality or tricuspid valve surgery and the number of heart failure hospitalizations. However, the primary endpoint was met only in certain patient populations.
The study failed when the analysis was limited to patients treated per protocol, and when COVID-19-related deaths and heart failure hospitalizations were included in the intent-to-treat analysis. The FDA wants the experts to discuss the “robustness” of the superiority of Triclip.
The superiority on the composite primary endpoint was driven by scores on a patient-reported outcome (PRO), namely the Kansas City Cardiomyopathy Questionnaire. Mortality and tricuspid valve surgery rates were similar in the two cohorts, according to the FDA’s executive summary, and the rate of heart failure hospitalization was numerically higher in people treated with Triclip.
Officials want experts to discuss the results in light of concerns about the use of PROs in open-label trials such as Triluminate. Participants “randomized to the investigational group may report more optimistic subjective information than patients in the control group,” the FDA wrote in the briefing document, and “concerns regarding the validity of PRO data in open-label trials seem reasonable.”
The FDA is also asking the experts to discuss the clinical significance of the numerically higher rates of all-cause mortality, cardiovascular mortality, heart failure hospitalization, tricuspid valve intervention, major bleeding and new onset renal failure in the Triclip cohort. The agency also wants the panel to examine the generalizability of the primary endpoint findings given that the device appeared to work better at sites that enrolled more patients.
Despite those issues, J.P. Morgan analysts see the document as positive for Abbott.
“We think the quality-of-life benefit is meaningful for these very sick patients, and Triclip demonstrated overall positive safety outcomes,” the analysts wrote. “With limited alternatives, we think this alone should be enough to drive approval and adoption despite the lack of a mortality/ hospitalization benefit, which the overall tone and substance of the briefing documents are supportive of as well.”