Milestone Pharmaceuticals Inc. announced the publication of results in TheLancet from the Phase 3 RAPID clinical trial evaluating etripamil nasal spray, the Company's investigational calcium channel blocker, in patients with supraventricular tachycardia (PSVT). Phase 3 RAPID Trial: The multi-center, randomized, double-blind, placebo-controlled RAPID trial enrolled 706 patients across clinical sites in North America and Europe. Patients were randomized 1:1 to self-administer a nasal spray of etripamil or placebo, as prompted by symptoms of PSVT, without medical monitoring and when an episode occurred in the course of daily activities.

To maximize the potential treatment effect of etripamil, patients who did not experience PSVT-symptom relief within 10 minutes were directed to self-administer a repeat dose of study drug. Pre- and post-drug ambulatory electrocardiographic (ECG) data were independently adjudicated in this event-driven trial. Key findings from the trial featured in the publication, which support the potential self-administration of etripamil outside of the healthcare setting, are summarized: The RAPID trial achieved its primary endpoint, with patients taking etripamil demonstrating a highly statistically significant and clinically meaningful difference in time to supraventricular tachycardia conversion compared to placebo.

A Kaplan Meier analysis showed a statistically significantly greater proportion of patients who took etripamil converted within thirty minutes compared to placebo (64.3% vs. 31.2%; hazard ratio [HR] = 2.62; 95% CI 1.66, 4.15; p<0.001). Significant reductions in time to conversion in patients who took etripamil were evident early and were durable, persisting throughout the observation window of the study compared to placebo, with a median time to conversion of 17.2 minutes (95% CI= 13·4, 26·5) for patients treated with etripamil versus 53.5 minutes (95% CI= 38.7, 87.3) for patients treated with placebo.

Data demonstrated statistically significant improvement in multiple defined symptoms of PSVT in patients receiving etripamil compared to placebo, using a patient-reported outcome (PRO) questionnaire. Reduction in emergency-department visits and, for example, need for intravenous treatments, was observed, though not with statistical significance in this dataset alone. The safety and tolerability data from the RAPID trial continue to support the potential self-administration of etripamil, with findings consistent with those observed in prior trials.

The most common randomized treatment emergent adverse events (RTEAEs), which are adverse events (AEs) that occurred within 24 hours of study drug administration, were related to the nasal administration site. Overall, the majority of RTEAEs were reported as mild (68%) to moderate (31%). There were no reported serious AEs related to etripamil.

As previously communicated, Milestone plans to submit a New Drug Application (NDA) filing in the third quarter of 2023.