Milestone Pharmaceuticals has enrolled the first patient in its Phase 3 ReVeRA-301 pivotal trial evaluating etripamil nasal spray for the acute treatment of Atrial Fibrillation with Rapid Ventricular Rate (AFib-RVR), advancing the company’s efforts to develop a self-administered treatment option for a condition that frequently requires urgent medical care.

The multinational, multicenter, randomised, double-blind, placebo-controlled Phase 3 study is expected to enroll approximately 150 adults with AFib-RVR. Participants will self-administer etripamil in a medically unsupervised setting, such as at home, using the same 70 mg dose and repeat-dose regimen evaluated in the pivotal programme for etripamil’s approved indication in paroxysmal supraventricular tachycardia (PSVT).

The primary endpoint of ReVeRA-301 is a reduction in ventricular rate within 30 minutes of treatment. The study will also assess symptom improvement through patient-reported outcomes.

Etripamil is a rapid-acting calcium channel blocker delivered through a nasal spray. In the United States, it is approved by the US Food and Drug Administration (FDA) as Cardamyst (etripamil) nasal spray for the conversion of acute symptomatic episodes of PSVT to sinus rhythm in adults.

The Phase 3 programme in AFib-RVR builds on findings from the Phase 2 ReVeRA-201 trial, which evaluated etripamil in patients experiencing symptomatic AFib-RVR in an emergency-room setting. The study found that a single 70 mg dose reduced ventricular rate and improved symptom relief and treatment satisfaction.

Atrial fibrillation is 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, patients may experience symptoms including palpitations, shortness of breath and weakness. Current acute treatment approaches frequently require medical evaluation and interventions such as intravenous beta blockers, intravenous calcium channel blockers or electrical cardioversion.

Milestone said the ReVeRA-301 trial is designed to determine whether etripamil could provide a potential self-administered treatment option that may reduce reliance on emergency department care for selected patients experiencing AFib-RVR.

The company is currently pursuing a single-study supplemental New Drug Application (sNDA) registration pathway for AFib-RVR based on the safety data generated to date.

David Bharucha, M.D., Ph.D., FACC, Chief Medical Officer of Milestone Pharmaceuticals, said, “Enrolling the first patient in the ReVeRA-301 phase 3 trial marks an important point in the development of etripamil for patients with AFib-RVR. FDA approval of etripamil for acute episodic PSVT and encouraging Phase 2 data in AFib-RVR provide a foundation for advancing the clinical programme.”

The trial is being activated at sites across North America and internationally. If successful, the study could support the development of a self-administered approach for managing acute episodes of AFib-RVR outside conventional healthcare settings.

Milestone Pharmaceuticals is an emerging commercial-stage biopharmaceutical company focused on developing and commercialising cardiovascular medicines for patients with heart conditions.