Milestone Pharma starts Phase 3 trial of etripamil for AFib-RVR
Milestone Pharmaceuticals has dosed the first patient in ReVeRA-301, its pivotal Phase 3 trial of etripamil nasal spray in atrial fibrillation with rapid ventricular rate (AFib-RVR). The Montreal and Charlotte-based biopharmaceutical company is evaluating the same 70 mg repeat-dose regimen already FDA-approved under the CARDAMYST brand for paroxysmal supraventricular tachycardia (PSVT), seeking a supplemental new drug application (sNDA) pathway into a second indication.
The trial is randomised, double-blind, and placebo-controlled, targeting enrolment of approximately 150 patients across sites in North America and internationally. Its primary endpoint is reduction in ventricular rate within 30 minutes of self-administration in a home or unsupervised setting, with symptom improvement via patient-reported outcomes as a key secondary endpoint. Milestone said it is pursuing a single-study sNDA registration pathway, supported by safety data accumulated to date.
Phase 2 foundation
ReVeRA-301 builds on the Phase 2 ReVeRA-201 study, conducted in an emergency department setting, which demonstrated that a single 70 mg dose of etripamil nasal spray reduced ventricular rate and improved both symptom relief and treatment satisfaction in AFib-RVR patients. The design shift to home self-administration in Phase 3 is clinically significant: if validated, it would offer patients a way to manage acute episodes without an emergency department visit.
James Ip, professor of medicine and director of cardiac pacing and implantable devices at Weill Cornell Medicine, and the study's principal investigator, highlighted the gap the trial is attempting to close. "Patients experiencing AFib-RVR have no optimally effective self-administered treatment options, meaning many require evaluation and treatment in the emergency department," he said. "We are eager to determine if we can clinically validate a safe and effective self-administered treatment option."
Market context and competitive landscape
The commercial rationale is substantial. AFib affects more than six million patients in the United States, and market research cited by Milestone suggests 30 to 40 per cent of those patients experience at least one RVR episode requiring urgent care per year. American Heart Association projections referenced in the release estimate the total US economic burden of AFib will rise from $59.4 billion in 2020 to $174.8 billion by 2050, with direct healthcare costs accounting for the majority of that figure.
Current acute management relies heavily on intravenous beta-blockers, intravenous calcium channel blockers, or electrical cardioversion, all of which require supervised clinical settings. No self-administered, patient-initiated option is currently approved for the indication, which is the gap Milestone is targeting. The self-administration angle also echoes a broader trend across cardiovascular medicine: regulators and payers are increasingly receptive to out-of-hospital management tools that can reduce emergency department pressure.
Milestone already has a commercial footprint with CARDAMYST in PSVT, which means manufacturing, safety pharmacovigilance, and prescriber education infrastructure are partially in place. That reduces execution risk for the AFib-RVR programme relative to a company launching a de novo asset. The company is also running a separate Phase 2 programme in paediatric PSVT, suggesting it is treating etripamil as a platform rather than a single-indication product.
Investors will focus on enrolment pace and the event-driven nature of the study design. Because episodes of AFib-RVR are episodic and unpredictable, enrolment timelines and the number of evaluable events can be harder to forecast than in conventional chronic-disease trials, and any slippage on that front is likely to draw scrutiny on a NASDAQ-listed small-cap.