FDA Pathway to Approval: Clinical Requirements for Renal Denervation Todd Courtney, MS Peripheral Interventional Devices Branch Division of Cardiovascular Devices Food and Drug Administration

Current Regulatory Status There are no cardiovascular devices approved for renal denervation.

Pre-Clinical Testing Animal Testing Bench testing Acute/Chronic Assess proof of concept for therapy Bench testing Use risk analysis to develop engineering tests Consider worst case scenario Biocompatibility, EMC/EMT, etc.

Patient Population Patients should have refractory hypertension. Systolic blood pressure ≥160 mmHg (≥150 mmHg for type 2 diabetics) Adhering to a stable drug regimen of 3 or more anti-hypertensive medications (including 1 diuretic) ABPM should be used to rule out ‘white coat’ hypertension No renal artery stenosis or anatomy that would be ineligible for treatment

Patient Population Blood pressure measurement should be objective for entry and baseline. Same devices and protocols to measure SBP/DBP There should be a run-in period to ensure patient is refractory. 2 weeks of blood pressure and medication monitoring Confirmation of refractory hypertension Office SBP > 160 mmHg Ambulatory blood pressure monitoring Medication compliance

Primary Endpoints Effectiveness: Improvement in blood pressure (6 mo) Systolic as primary endpoint Should be clinically meaningful, not just a statistically significant decrease as compared to a control or performance goal Reduction should be sustained. Safety: MAE compared to other renal interventions at 6 mo. MAE based on literature rates of renal interventions Death, stroke, MI, perforation, dissection, etc. Study should be powered for both safety and effectiveness

Secondary Analyses Important because first device will go to panel Secondary analyses should investigate How patients fare depending on entry blood pressure Reduction in medications Treatment number of medications DBP improvement Correlation of ambulatory and office-based BP

Important Considerations First-in-Man study important to assess proof of concept Prefer a randomized trial, because there isn’t robust control data. Follow-up at 1, 3, 6, 9, 12 months for year 1; every 6 months thereafter. Long term follow-up to assess sustainablility of treatment effect. Post-market study to assess effect of therapy on broader population

Other Considerations Early Feasibility Study Presubmission program Allows for early clinical evaluation of devices to provide proof of principle and initial clinical safety data. Appropriate early in device development when clinical experience is necessary because nonclinical testing methods are not available or adequate to provide the information needed to advance the developmental process. Presubmission program Old pre-IDE submission process

Todd Courtney todd.courtney@fda.hhs.gov 301-796-6371 Thank You! Todd Courtney todd.courtney@fda.hhs.gov 301-796-6371