On October 17, Milestone Pharmaceuticals announced positive data from the Phase III RAPID study of the inhaled calcium channel blocker Etripamil in the treatment of paroxysmal supraventricular tachycardia, and plans to submit a marketing application in mid-2023.
Paroxysmal supraventricular tachycardia (PSVT) is a rapid heart rate state characterized by intermittent episodes of supraventricular tachycardia, often accompanied by symptoms such as palpitations, sweating, chest tightness, shortness of breath, and dizziness. Certain calcium channel blockers are currently approved globally to treat PSVT and other heart conditions, but these drugs must be administered intravenously under physician supervision, usually in emergency departments or other acute care settings.
Etripamil, a novel calcium channel blocker and a self-administered nasal spray that patients can use at home, promises to change the treatment paradigm for PSVT. Milestone is conducting a comprehensive clinical development program for Etripamil, including a Phase III study of PSVT and a Phase II proof-of-concept trial in patients with atrial fibrillation. To date, more than 1,600 patients have been treated with Etripamil at doses ≥70 mg.
RAPID was a randomized, double-blind, placebo-controlled study that enrolled 706 patients. In the absence of medical monitoring, these patients were randomized 1:1 to receive Etripamil or a placebo nasal spray. To maximize the potential therapeutic effect of Etripamil, patients whose symptoms did not improve within 10 minutes were prompted to self-administer repeated doses of the drug.
The results showed that patients treated with Etripamil showed a statistically and clinically meaningful benefit in the length of time to return to sinus rhythm from PSVT compared to the placebo group. 64.3% of patients in the Etripamil group recovered within 30 minutes, compared with 31.2% in the placebo group ([HR]=2.62; 95% CI: 1.66, 4.15; P<0.001).
In addition, patients in the Etripamil group had a median recovery time three times faster than in the placebo group. Etripamil prompted many patients to experience symptom relief early on in treatment, and this improvement persisted throughout the study.
In a pooled analysis of the NODE-301 and RAPID studies, Etripamil treatment significantly reduced the use of other medical interventions and was statistically significant in reducing emergency department visits.
Overall, the drug was safe and well-tolerated, with the most common treatment-related adverse events related to the nasal administration site, which were mild (68%) to moderate (31%). No patients reported serious adverse reactions related to Etripamil.
In March 2020, Etripamil’s Phase III NOTD-301 study in PSVT patients failed to meet its primary endpoint of restoring sinus rhythm within 5 hours of dosing. Notably, the benefit of Etripamil was more pronounced within 45 minutes after administration. At the time, the company said two factors, a small number of placebo patients and an extended period of efficacy measurement, had interfered with the study results.
“The success of the RAPID study marks an important achievement for our company and for patients with PSVT,” said Joseph Oliveto, President and CEO of Milestone. “We believe that if Etripamil is approved, it will have the potential to enable patients to take control of their condition and protect health insurance. The system provides value in part by reducing the number of emergency patient visits. We look forward to working with the FDA to provide the first self-administered therapy of its kind.”