Milestone Pharma enrols first European patient in AFib-RVR trial
Milestone Pharmaceuticals has enrolled its first European participant in ReVeRA-301, the ongoing Phase 3 pivotal study of etripamil nasal spray for atrial fibrillation with rapid ventricular rate (AFib-RVR). The patient was enrolled through the Dutch Cardiovascular Investigator Network (WCN) in the Netherlands, extending a trial that launched in the United States in August 2026 and has since added Canadian sites.
ReVeRA-301 is a randomised, double-blind, placebo-controlled study targeting approximately 150 patient events. Participants self-administer a 70 mg dose of etripamil in an unsupervised setting, such as at home, and may repeat the dose according to the same regimen already approved by the FDA for paroxysmal supraventricular tachycardia (PSVT) under the brand name CARDAMYST. The primary endpoint is reduction in ventricular rate within 30 minutes; secondary endpoints include patient-reported symptom improvement.
Trial design and regulatory context
Milestone is pursuing a single-study supplemental new drug application pathway for AFib-RVR, based on safety data gathered to date. That strategy places considerable weight on ReVeRA-301 delivering a clean dataset, since there is no separate confirmatory study planned at this stage. The Phase 2 predecessor, ReVeRA-201, studied etripamil in an emergency room setting and showed that a single 70 mg dose reduced ventricular rate and improved symptom relief and treatment satisfaction.
Chief Medical Officer David Bharucha said the WCN collaboration, which began during ReVeRA-201, provides a solid foundation for the Phase 3 programme. Martin Hemels, cardiologist and chair of WCN, said the trial "explores a novel approach that could help patients receive effective treatment earlier and potentially avoid hospital visits."
Market context and competitive positioning
The commercial rationale for etripamil in AFib-RVR is rooted in the limitations of current acute management. Most patients experiencing an AFib-RVR episode require an emergency department visit for intravenous rate-control agents such as beta blockers or calcium channel blockers, or electrical cardioversion. Milestone estimates that 30 to 40 per cent of AFib patients experience at least one RVR episode per year requiring urgent attention, drawing on a global AFib population the company puts at around 59 million people.
A self-administered nasal spray that avoids hospital admission would carry meaningful health-economic appeal for payers, particularly in European systems under pressure to reduce unplanned attendances. No directly comparable self-administered acute rate-control product is currently approved in the indication, which gives etripamil a relatively clear regulatory lane if efficacy holds at Phase 3. However, the acute arrhythmia space is well served by generic intravenous agents at low cost, meaning the commercial argument will rest heavily on patient convenience and quality-of-life data rather than clinical superiority alone.
Milestone's ability to secure European approval will also depend on whether EMA accepts the single-study sNDA strategy mirrored at the FDA, or requires additional data. With enrolment now active across three territories, the company's next disclosed milestone is completion of the 150-event target, after which topline data and a regulatory submission timeline should follow.