Milestone® Pharmaceuticals Inc. announced that the Company received a Refusal to File (RTF) letter from the U.S. Food and Drug Administration (FDA) for the New Drug Application (NDA) for self-administered etripamil nasal spray for the treatment of paroxysmal supraventricular tachycardia (PSVT). Upon preliminary review, the FDA determined that the NDA, submitted in October 2023, was not sufficiently complete to permit substantive review. The FDA requested clarification about the time of data recorded for adverse events in Phase 3 clinical trials; FDA did not express concerns about the nature or severity of adverse events.

Milestone will seek clarification and is in the process of planning a meeting with the FDA. Recently published in The Lancet, RAPID is a global, randomized, double-blind Phase 3 clinical trial of etripamil versus placebo in patients with PSVT. The trial was designed to evaluate the safety and efficacy of self-administered etripamil for treating PSVT.

RAPID achieved its primary endpoint with 64% of patients who self-administered etripamil converting from supraventricular tachycardia (SVT) to sinus rhythm within 30 minutes compared to 31% on placebo (HR = 2.62, p<0.001). At one hour, the benefit was demonstrated in 73% of patients. In addition, significant reductions in time to conversion in patients who took etripamil were evident early and durable, with a median time to conversion of 17 minutes (95% CI: 13.4, 26.5) for patients treated with etripamil versus 54 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. The safety and tolerability profile of etripamil is supportive of the NDA submission. An estimated two million people in the United States are currently diagnosed with PSVT which is a type of arrhythmia or abnormal heart rhythm.

PSVT is characterized by episodes of rapid heartbeats often exceeding 150 to 200 beats per minute. Key features of PSVT include the sudden occurrence of episodes and very rapid heart rate. The heart rate can spike unpredictably and rapidly during an episode.

The rapid heart rate often causes severe palpitations, shortness of breath, chest discomfort, dizziness, or lightheadedness, and distress, forcing patients to limit their daily activities. The uncertainty of when an episode of PSVT will strike or how long it will persist can provoke anxiety in patients and negatively impact their day-to-day life between episodes. The impact and morbidity from an attack can be especially detrimental in patients with underlying cardiovascular or medical conditions, such as heart failure, obstructive coronary disease, or dehydration.

Many health care providers are dissatisfied with the lack of effective treatment options in addition to a prolonged, burdensome, and costly trip to the emergency department or, for some patients, an invasive ablation procedure.