Etripamil nasal spray was shown in a post-hoc analysis to resolve paroxysmal supraventricular tachycardia faster and more completely than placebo in most patients and reduced the number of emergency room visits for additional interventions.
May 16, 2020 — New data from in the NODE-301 Trial for the patient-administered nasal spray etripamil to resolve paroxysmal supraventricular tachycardia (PSVT) found the drug helps reduce emergency room visits and significantly reduced symptoms as compared to placebo. This was the finding of a new post-trial data analysis presented at the American College of Cardiology (ACC) 2021 virtual scientific session.
The trial data originally presented at the 2020 Heart Rhythm Society (HRS) meeting found etripamil did not meet its primary endpoint, because placebo outperformed the drug in PSVT. This new data is a post-hoc analysis of the NODE-301 study looked more closely at the timing of the PSVT resolution in a shorter time frame and factors such as resolution of symptoms and visits to the emergency room.
"This secondary analysis did show a clinically meaningful early treatment effect, showing etripamil 70mg was significantly more effective than placebo nasal spray in converting PSVT in the first 45 minutes," explained Bruce Stambler, M.D., FHRS, Piedmont Heart Institute, Atlanta, Ga., who presented the new data at ACC.21.
He said relief of PSVT symptoms was significantly higher with etripamil vs. placebo, including reductions across the board for rapid pulse, palpitations, dizziness, anxiety, shortness of breath and chest pain.
The post-hoc study also looked more closely at patient reported satisfaction using the nine question treatment satisfaction questionnaire for medication (TSQM-9). Global patient satisfaction for the drug was 57 vs. 43% for placebo. Treatment effectiveness was 54 vs. 35% in favor of etripamil.
Stambler also said patients on placebo were more likely to seek additional interventions to relieve their symptoms. Only 14% of etripamil patients sought additional, while 26.5% of placebo patients sought additional interventions. This included emergency room (ER) visits or taking additional prescribed medications. Of the patients seeking ER help, 12.1% were in the etripamil group and 24.5 were in the placebo group, which Stambler said shows a 51% reduction in ER visits. Of the 25 patients who sought help in an ER, interventions included IV adenosine in 20 patients.
The drug from Milestone Pharmaceuticals Inc. is a novel short-acting calcium channel blocker. The trial enrolled a total of 431 patients across 65 sites in the U.S. and Canada, is an event-driven Phase 3 efficacy trial of etripamil for terminating supraventricular tachycardia (SVT) episodes in the at-home setting.
The data presented in 2020 showed etripamil (70 mg) did not achieve its primary endpoint of time to conversion of SVT to sinus rhythm (SR) compared to placebo over the five hour period following study drug administration (median time to conversion of 25 minutes [95% CI: 16, 43] for etripamil vs. 50 minutes [95% CI: 31,101] for placebo, p=0.12). Despite early activity, including the conversion of 61% of etripamil patients vs. 45% of placebo patients by 45 minutes (p=0.02), a time period consistent with etripamil's known pharmacological activity, results from the latter part of the analysis confounded the statistical analysis of the primary endpoint.
The study did demonstrate statistically significant improvements in favor of etripamil over placebo in the important secondary endpoint of patient reported treatment satisfaction, as measured by TSQM-9 questionnaire, including global satisfaction (p=0.0069) and effectiveness scores (p=0.0015), with questions addressing the relief of symptoms commonly associated with an episode of SVT, such as rapid pulse, heart palpitations, anxiety, shortness of breath and dizziness. Additionally, there was a trend in improvement in the percentage of patients seeking rescue medical intervention, including in the emergency department, with etripamil and placebo patients reporting 15% and 27%, respectively (p=0.12).
The safety and tolerability data from the NODE-301 study are supportive of at-home use of etripamil, with adverse events (AE) consistent with those observed in prior trials. The most common AEs observed in patients receiving etripamil were local to the nose, including nasal irritation and congestion, and these events were typically transient in nature and most commonly characterized by the patient as mild in severity. There were no significant differences in incidences of severe adverse events or adverse events of interest, such as atrioventricular nodal blocks or blood pressure-related symptoms, across the etripamil and placebo groups.
The NODE-301B study, which was designed to collect double-blind data from randomized patients who had not yet experienced an event after the NODE-301 trial reached its target number of adjudicated SVT events, continues. These data will be analyzed separately as a second data set. In addition, open-label safety studies of etripamil in subjects with PSVT, NODE-302 and NODE-303, are ongoing with active recruitment underway. The Company is actively monitoring the potential impact of the COVID-19 pandemic on its ongoing trials and will provide updates on any delayed timelines or cost impacts in the future. Milestone Pharmaceuticals expects to request a meeting with regulators to discuss the NODE-301 results and its ongoing studies.
Read more about the HRS 2020 data in the article Etripamil Nasal Spray Does Not Meet Primary Endpoint in Treating Supraventricular Tachycardia.
The drug was first discussed in the HRS 2017 late-breaking sessions and the early results appeared very promising. Read more in the article First Nasal Spray Successfully Treats Supraventricular Tachycardia.
What is Paroxysmal Supraventricular Tachycardia?
Paroxysmal supraventricular tachycardia (PSVT) is a rapid heart rate condition characterized by intermittent episodes of supraventricular tachycardia (SVT) that start and stop suddenly and without warning. Episodes of SVT are often associated with symptoms including palpitations, sweating, chest pressure or pain, shortness of breath, sudden onset of fatigue, lightheadedness or dizziness, fainting, and anxiety. Certain calcium channel blockers have long been approved for the treatment of PSVT as well as other cardiac conditions; however, when calcium channel blockers are used for the termination of SVT episodes, they must be administered intravenously under medical supervision, usually in an emergency department or other acute care setting.