Milestone Starts Phase 3 Trial for AFib-RVR Therapy

Montreal, Canada, and Charlotte, North Carolina, USA, August 21, 2026

ReVeRA-301 Evaluates Self-Administered AFib Treatment

The ReVeRA-301 Phase 3 study is a multinational, multicenter, randomized, double-blind, placebo-controlled trial expected to enroll approximately 150 patients with AFib-RVR. Participants experiencing symptoms will self-administer etripamil nasal spray in a medically unsupervised setting, such as at home. The study is evaluating the 70 mg dose and repeat-dose regimen already used in the pivotal development program supporting etripamil’s FDA-approved PSVT indication. The primary endpoint is reduction in ventricular rate within 30 minutes, while a key secondary endpoint will assess improvement in symptoms through patient-reported outcomes. The company is pursuing a potential single-study supplemental New Drug Application (sNDA) pathway for AFib-RVR based on the safety information available to date. The Phase 3 program builds on findings from the earlier ReVeRA-201 Phase 2 trial, which evaluated etripamil nasal spray for acute reduction of symptomatic AFib-RVR in an emergency-room setting. According to the company, the Phase 2 study showed that a single 70 mg dose reduced ventricular rate and improved symptom relief and treatment satisfaction. ReVeRA-301 is intended to further evaluate these findings in a larger, controlled clinical study and assess whether patients can safely administer the treatment when an AFib-RVR episode occurs.

AFib-RVR Creates Significant Unmet Medical Need

Atrial fibrillation (AFib) is described as the most common sustained cardiac arrhythmia and affects more than 6 million people in the United States. When AFib is accompanied by a rapid ventricular rate, it is referred to as AFib-RVR. Episodes may cause symptoms including palpitations, shortness of breath, and weakness, and patients may require urgent medical evaluation and treatment. Current acute management frequently involves emergency-department care, where patients may receive intravenous beta blockers, intravenous calcium channel blockers, or electrical cardioversion depending on their clinical circumstances. The need for acute treatment also contributes to a substantial healthcare burden. The company cites market research indicating that approximately 30% to 40% of patients with AFib experience at least one RVR episode each year requiring urgent medical attention. U.S. healthcare data cited in the release showed increasing emergency-department utilization associated with AFib, while the American Heart Association has projected a substantial increase in the overall economic burden of AFib in the United States through 2050. These factors highlight the potential importance of treatment approaches that could provide patients with greater flexibility in managing acute episodes.

Etripamil Advances Beyond Approved PSVT Use

Etripamil is a novel calcium channel blocker delivered through a nasal spray, designed to provide a rapid-response treatment option that can be administered without immediate medical oversight. The therapy is already FDA approved as CARDAMYST® for the conversion of acute symptomatic PSVT episodes to sinus rhythm in adults. Milestone is now investigating whether the same therapeutic approach can be extended to acute AFib-RVR episodes in adults. The initiation of ReVeRA-301 represents an important clinical development milestone for Milestone Pharmaceuticals and its cardiovascular pipeline. However, etripamil’s safety and efficacy for AFib-RVR remain under investigation, and the Phase 3 study will be necessary to determine whether the treatment can demonstrate the required clinical benefit and safety profile. If successful, the program could support a future regulatory submission seeking to expand etripamil’s use into self-administered management of AFib-RVR, potentially offering another approach for patients experiencing acute episodes.

Source: Milestone Pharmaceuticals press relese