Etripamil Nasal Spray Shows Promise in AFib with Rapid Ventricular Rates


An analysis of data from the NODE-303 trial provides insight into the effects of etripamil nasal spray in people with atrial fibrillation with rapid ventricular rates.

Paul Dorian, MD, MSc | Credit: St. Michael's Hospital

Paul Dorian, MD, MSc
Credit: St. Michael's Hospital

New data is providing additional insight into the effects of etripamil nasal spray for reducing ventricular rates following self-administration in patients with atrial fibrillation and rapid ventricular rates.

Presented at the Heart Rhythm 2023 Annual Meeting, results of the study, which was an analysis of data from the NODE-303 trial, provide an updated overview of the efficacy and safety of self-administration following symptoms of rapid ventricular rate among patients with atrial fibrillation with rapid ventricular rates (AFib-RVR) rather than paroxysmal supra ventricular tachycardia (PSVT).1

"AFib-RVR frequently causes severe symptoms and anxiety. Slowing the heart rate quickly can offer considerable relief from both symptoms and associated concerns. Etripamil nasal spray, an investigational treatment, would be the only self-administered medication available which suits this purpose," said lead author Paul Dorian, MD, MSC, professor of medicine and pharmacology at University of Toronto and staff cardiac electrophysiologist at St. Michael's Hospital.2 "These initial results are encouraging and support further clinical development of etripamil and highlight the potential of etripamil to offer patients a valuable option to manage their AFib-RVR episodes outside of the stressful and costly acute-care setting."

A phase 3 clinical research trial, the NODE-303 study was launched with the intent of exploring whether use of etripamil nasal spray could provide patients with a safe and efficacious medication for ending PSVT episodes. Per trial protocol, patients were given a cardiac monitoring system to record episodes of PSVT and were asked to complete assessments to track experience with etripamil nasal spray. The overall trial enrolled a cohort of 1118 patients. Among this cohort, total of 1024 treated episodes of arrhythmia, including 26 episodes investigators attributed to AFib-RVR rather than PSVT.1

In the current study, a team of investigators lead by Dorian sought to explore the specific effects of etripamil nasal spray from the trial among the subgroup of patients with AFib-RVR. Of the 26 episodes, a group of 21 episodes had sufficiently interoperable ECG data and were included in the analysis. At baseline, the mean ventricular rate among this cohort was 129.7±5.4 beats per minute and, among the 21 episodes included, 17 had a ventricular rate of 110 beats per minute or greater at baseline.1

For the purpose of analysis, the primary outcomes difference was the differences between initial ventricular rates and ventricular rates at 1-min following intervals were calculated for each episode during the 60-minutes period following drug receipt. Investigators noted ventricular rate data after conversion to sinus rhythm were excluded.1

Of the 21 episodes included in the study, 6 episodes converted to sinus rhythm with use of etripamil nasal spray. Results of the investigators’ analyses indicated there was a maximum reduction of ventricular rate of -27±6.1 beats per minute at 22 minutes and -16.2±5.6 beats per minute at 60 minutes. Analysis of safety and tolerability data were consistent with those observed across prior studies in PSVT. Investigators noted the overall majority of adverse events reported were classified as mild to moderate, with no serious adverse events reported related to use of etripamil.1

"Data from this unplanned analysis represent the first direct clinical evidence of the impact of etripamil on heart rate in patients experiencing an event of AFib-RVR," said Joseph Oliveto, President and Chief Executive Officer of Milestone Pharmaceuticals.2 "We look forward to sharing topline results from our ongoing Phase 2, placebo-controlled study in patients with AFib-RVR, which we expect to report in the second half of 2023. We are firmly committed to our mission of unlocking the full potential of etripamil to serve as a self-administered, on-demand treatment for patients facing episodic cardiovascular conditions associated with rapid heart rate."

In a press release from March 2023, Milestone Pharma noted places to use data from the NODE-303 and phase 3 RAPID trials as part of a New Drug Application submission to the US Food and Drug Administration in Q3 of 2023.3


  1. Dorian P, Alings AM, Benoit C, et al. Effect of Etripamil Nasal Spray on Ventricular Rate in Patients Experiencing Symptomatic Atrial Fibrillation. Paper presented at: Heart Rhythm 2023. New Orleans, LA. May 19 – 21, 2023.
  2. Milestone Pharmaceuticals announces presentation of data from analysis of Etripamil nasal spray in patients experiencing atrial fibrillation with rapid ventricular rate. Milestone Pharmaceuticals, Inc. May 22, 2023. Accessed May 23, 2023.
  3. Milestone Pharmaceuticals progresses clinical and regulatory activities for Etripamil in patients with paroxysmal supraventricular tachycardia. Milestone Pharmaceuticals, Inc. March 6, 2023. Accessed May 23, 2023.

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