Milestone Pharma enrols first Canadian patient in AFib-RVR trial

Milestone Pharmaceuticals has enrolled its first Canadian participant in ReVeRA-301, its Phase 3 pivotal trial evaluating etripamil nasal spray for atrial fibrillation with rapid ventricular rate (AFib-RVR). The Montreal Heart Institute becomes the first Canadian site activated in the multinational study, which is targeting approximately 150 patient events in total. The Canadian enrolment follows the first US participant enrolled earlier this year.

ReVeRA-301 is a randomised, double-blind, placebo-controlled study in which participants self-administer etripamil at home when symptoms arise, rather than in a supervised clinical setting. The primary endpoint is reduction in ventricular rate within 30 minutes, with patient-reported symptom improvement as a key secondary measure. Milestone is pursuing a supplemental new drug application pathway with the FDA, meaning a single successful study could support label expansion.

Building on an approved product

Etripamil nasal spray is already FDA-approved under the brand name CARDAMYST for the conversion of paroxysmal supraventricular tachycardia to sinus rhythm in adults, using the same 70 mg repeat-dose regimen being evaluated in ReVeRA-301. That existing approval gives Milestone a meaningful regulatory starting point: the safety profile of the drug is established, and the sNDA route requires only one pivotal trial rather than a full new drug application programme.

Phase 2 data from the ReVeRA-201 study, conducted in an emergency room setting, showed that a single 70 mg dose reduced ventricular rate and improved symptom relief and treatment satisfaction. The Phase 3 design shifts the treatment setting from emergency departments to unsupervised home use, which raises both the commercial opportunity and the regulatory bar for safety monitoring.

Adrian Petzl, cardiologist-electrophysiologist at the Montreal Heart Institute and an investigator on the trial, said that "the ability to intervene promptly with a self-administered therapy outside of the emergency department could represent a meaningful change for patients living with this condition."

Market context and competitive landscape

AFib is the most common sustained cardiac arrhythmia, with an estimated six million patients in the United States alone and up to 800,000 in Canada according to the Canadian Cardiovascular Society. Market research cited by Milestone suggests that 30 to 40 per cent of AFib patients experience at least one rapid ventricular rate episode per year requiring urgent attention, with current management typically involving an emergency department visit for intravenous rate-control agents or cardioversion.

The self-administration angle is the differentiating claim for etripamil in AFib-RVR. No approved self-administered acute rate-control option currently exists in this indication in the US or Canada, and a successful Phase 3 readout would address a gap that generates significant healthcare resource use. Several companies are active in the broader AFib space, though most competitors focus on rhythm control, anticoagulation, or ablation technologies rather than acute episodic rate management via a nasal route.

With 150 patient events targeted across multiple countries, ReVeRA-301 is a relatively compact Phase 3 study by cardiovascular standards. Enrolment pace will be a key indicator to watch: the episodic, symptom-prompted design means that patient recruitment and event capture timelines are harder to predict than in continuous-dosing trials. Investors will be looking for interim updates on site activation and event rates as the trial matures into 2027.