Slide 1: Efficacy and Safety of Etripamil Nasal Spray for Acute Reduction of Rapid Ventricular Rate in AF
#AHA23 EFFICACY AND SAFETY OF ETRIPAMIL NASAL SPRAY FOR THE ACUTE REDUCTION OF RAPID VENTRICULAR RATE IN PATIENTS WITH ATRIAL FIBRILLATION: PHASE 2 ReVeRA-201 A. John Camm1, Jonathan Piccini2, Marco Alings3, Paul Dorian4, Gilbert Gosselin5, James Ip6, Peter Kowey7, Blandine Mondesert8, Fransisco J P
Slide 2: Disclosures
DISCLOSURES Marco Alings Honoraria/speaking/consulting fee: Sanofi, Milestone Pharmaceuticals AJ Camm Honoraria/speaking/consulting fee: Abbott, Acesion, Anthos Therapeutics, ARCA Biopharma, Bayer Healthcare Pharmaceuticals, Biotronik, Boston Scientific, Bristol Myers Squibb, Daiichi, InCarda Therap
Slide 3: Etripamil: Potential Treatment for AF with RVR
ETRIPAMIL: POTENTIAL TREATMENT FOR AF WITH RVR • Novel, investigational, L-type calcium channel blocker1,2 • Formulated for intranasal spray with: • Rapid onset of action (Tmax ≤ 7 min)3 • Short-lasting plasma exposure: inactivated by blood esterases4 • Developed to satisfy unmet need for self- admi
Slide 4: ReVeRA Study Design
REVERA STUDY DESIGN Objective - To assess the safety and efficacy of intranasal etripamil vs placebo to acutely reduce VR in patients with AF-RVR Screening & Treatment Visit Outcome measures Primary endpoint Study sites ▪ Mean maximum reduction in VR within 60 min RANDOMIZATION (1:1) DOUBLE-BLIND DR
Slide 5: ReVeRA Patient Disposition
REVERA PATIENT DISPOSITION The Safety Population is all randomized patients receiving study drug. The mITT Population is all randomized patients receiving study drug and who had a post-drug ECG CMS recording. The Efficacy Population is all randomized patients who remained in atrial fibrillation with
Slide 6: Demographics & Baseline Characteristics (Safety Population)
DEMOGRAPHICS & BASELINE CHARACTERISTICS (SAFETY POPULATION) Placebo Etripamil Overall (N=29) (N=27) (N=56) Age, Years Mean (SD) 64.59 ± 10.53 64.63 ± 10.61 64.6 (10.47) Median (range) 66.00 (35.00, 83.00) 64.00 (45.00, 88.00) 65 (35.00, 88.00) Sex, Female, n (%) 11 (37.9%) 11 (40.7%) 22 (39.3) Site
Slide 7: Efficacy Results - Primary Analysis
EFFICACY RESULTS - PRIMARY ANALYSIS Placebo NS1 Etripamil NS, 70 mg1 N=25 N=24 Baseline Ventricular Rate (bpm)2 Mean ± SD 135.54 ± 13.93 130.33 ± 15.28 Median (IQR) 135.40 (125.00, 140.20) 126.90 (122.40, 141.60) Nadir (bpm)3 Mean ± SD 130.66 ± 16.37 95.18 ± 23.68 Median (IQR) 132.20 (
Slide 8: Efficacy Endpoints – Mean VR Change from Baseline
EFFICACY ENDPOINTS – MEAN VR CHANGE FROM BASELINE 60 min plot 180 min plot Primary Endpoint (Efficacy Population) Maximum Reduction in VR adjusting for Placebo NS1 Etripamil NS, 70 mg1 Separation of curves baseline VR (bpm) N=25 N=24 (mITT Population) Adjusted mean (95% CI) -5.06 (-7.44, -2.67) -34.
Slide 9: Secondary Analyses
SECONDARY ANALYSES Placebo NS1 Etripamil NS1 70 mg n=25 n=24 Elapsed Time (Minutes) from Drug Administration to Nadir2 Median (IQR) 31.00 (18.00, 51.00) 13.00 (8.50, 28.50) Adjusted mean (95% CI) 32.66 (24.89, 40.43) 20.56 (12.63, 28.49) Difference of Means -- -12.10 (-23.29, -0.91) p-value3 -- 0.03
Slide 10: Achievement of VR <100 bpm or Reduction of ≥10% or ≥20%
ACHIEVEMENT OF VR <100 BPM OR A REDUCTION OF ≥10% OR ≥20% FROM BASELINE BY 60 MINUTES Placebo NS (n=251) vs. Etripamil NS, 70 mg (n=241) Patients Achieving a VR <100 bpm Placebo NS, n=251 Etripamil NS, 70 mg, n=241 Patients Achieving a ≥10% reduction <0.0001 n (%) 1 (4.0) 14 (58.3) in VR from ba
Slide 11: ReVeRA TSQM-9 PRO Assessment and Results
REVERA TSQM-9 PRO1 ASSESSMENT AND RESULTS • Three TSQM-9 Domains: Effectiveness, Global Satisfaction, & Convenience • Three questions per domain, each answered on 7-point anchored scale 1 2 3 4 5 6 7 Extremely Very Somewhat Very Extremely Dissatisfied Satisfied Dissatisfied Dissatisfied Satisfied Sa
Slide 12: Treatment-Emergent Adverse Events
TREATMENT-EMERGENT ADVERSE EVENTS Most common TEAEs ≥ 5%, Patients with ≥ 1 TEAEs (Safety population) Placebo NS1 (n= 29) Etripamil NS1 (n=27) Respiratory, Thoracic, and Mediastinal disorders Epistaxis -- 2 (7.4%) Nasal Congestion 1 (3.4%) 2 (7.4%) Nasal Discomfort 11 (37.9%) 16 (59.3%) Oropharyngea
Slide 13: ReVeRA Phase 2 Study: Summary and Conclusions
REVERA PHASE 2 STUDY: SUMMARY AND CONCLUSIONS • The ReVeRA trial showed that etripamil NS demonstrated substantial reduction in VR in patients with AF-RVR (difference between etripamil vs. placebo in maximum reduction from baseline: -29.91 bpm; p < 0.0001) • Median time to maximum reduction of 13 mi
Slide 14: Acknowledgements
ACKNOWLEDGEMENTS Canada Sites Jean-Francois Roux, Trial Networks Sherbrooke, QC Amir Abdel-Wahab, Halifax, NS Montreal Health Innovations Annie Roy, Laval, QC Coordinating Center (MHICC) Fabian Alejandro Azzari, Rimouski, QC Ian Stiell, Ottawa, ON Denis Roy, Principal Investigator Miguel Barrero, Tr
Slide 15: Simultaneous Publication: ReVeRA Study in Circulation: Arrhythmia and Electrophysiology
#AHA23 Simultaneous Publication: The ReVeRA Study is published on-line, Circulation: Arrhythmia and Electrophysiology https://www.ahajournals.org/doi/10.1161/CIRCEP.123.012567 A Multicenter, Phase 2, Randomized, Controlled Study of the Efficacy and Safety of Etripamil Nasal Spray for the Acute Reduc
Slide 16: Thank You!
EFFICACY AND SAFETY OF SELF-ADMINISTERED ETRIPAMIL NASAL SPRAY FOR THE ACUTE REDUCTION OF RAPID VENTRICULAR RATE IN PATIENTS WITH ATRIAL FIBRILLATION: PHASE 2 REVERA-201 #AHA23 THANK YOU!