Milestone Pharmaceuticals Inc., a biopharmaceutical company focused on the development and commercialization of innovative cardiovascular medicines, announced topline results from its Phase III, multicenter, randomized, double-blind, placebo-controlled NODE-301 trial of its investigational new drug, etripamil nasal spray, the Company's novel short-acting calcium channel blocker, in patients with paroxysmal supraventricular tachycardia (PSVT).
The NODE-301 trial, which enrolled a total of 431 patients across 65 sites in the U.S. and Canada, is an event-driven Phase III efficacy trial of etripamil for terminating supraventricular tachycardia (SVT) episodes in the at-home setting. Etripamil (70mg) 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 demonstrated statistically significant improvements in favor of etripamil over placebo in the important secondary endpoint of patient reported treatment satisfaction, as measured by a treatment satisfaction questionnaire for medication (TSQM-9), 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.