European Medicines Agency accepts marketing authorization application for etripamil nasal spray in PSVT – Milestone Pharmaceuticals

Milestone Pharmaceuticals Inc. announced the acceptance of a Marketing Authorization Application (MAA) by the European Medicines Agency (EMA) seeking the approval of etripamil nasal spray, developed to be the first rapid, reliable option in the treatment of paroxysmal supraventricular tachycardia (PSVT) outside of the healthcare setting. Etripamil, which has the conditionally approved brand name Tachymist in Europe, is an investigational, novel calcium channel blocker delivered via a nasal spray by the patient for the potential treatment of PSVT and other cardiac arrhythmias. A decision on approval is expected by the first quarter of 2027.

“Following guidance from the EMA, this MAA incorporates the global clinical data package that supported the U.S. Food and Drug Administration approval of etripamil for the treatment of PSVT,” said Joseph Oliveto, President and Chief Executive Officer of Milestone Pharmaceuticals. “Tachymist could become the first approved patient self-administered therapy representing a meaningful step forward in patient care for the approximately two million people suffering from PSVT in Europe.”

About the Pivotal RAPID Phase III Trial
The MAA submission is supported by efficacy, safety, and tolerability results from a robust clinical trial program based on data from more than 1,800 participants and more than 2,000 episodes of PSVT. This includes the successful Phase III RAPID trial, a global, randomized, double-blind comparison of etripamil vs. placebo, published in The Lancet in 2023. In clinical studies, participants using etripamil were two times more likely to convert symptomatic PSVT to sinus rhythm and did so more than three times faster compared with placebo. The RAPID trial achieved its primary endpoint with 64% of those who self-administered etripamil (N=99) converting from PSVT to sinus rhythm within 30 minutes compared to 31% on placebo (N=85) (HR=2.62; p<0.001). At one hour, the benefit was demonstrated in 73% of participants. In addition, significant reductions in time to conversion in those who took etripamil were evident early and were durable, with a median time to conversion of 17 minutes (95% CI: 13.4, 26.5) for those treated with etripamil vs. 54 minutes (95% CI: 38.7, 87.3) for those treated with placebo. A consistent safety profile and treatment effects were observed across all subgroups, including participants concurrently on beta blockers or calcium channel blockers. The most frequent adverse events occurring in ≥5% of participants in randomized clinical trials were mild-to-moderate and transient in nature, including local-site nasal discomfort, nasal congestion, rhinorrhea, throat irritation, and epistaxis. Less than 2% of trial participants discontinued therapy due to adverse events.

Citation: Self-administered intranasal etripamil using a symptom-prompted, repeat-dose regimen for atrioventricular-nodal-dependent supraventricular tachycardia (RAPID): a multicentre, randomised trial. Authors: Bruce S Stambler, MD ∙ Prof A John Camm, MD ∙ Marco Alings, MD et al. Published June 15, 2023 The Lancet. DOI: 10.1016/S0140-6736(23)00776-6