New data from the Phase 3 RAPID clinical trial of etripamil, an investigational calcium channel blocker nasal spray, showed positive results in converting paroxysmal supraventricular tachycardia (PSVT) to normal sinus rhythm in the at-home setting. The presentation was featured during a late-breaking clinical trials session at the American Heart Association (AHA) 2022 Scientific Sessions.
The drug allows patients to take control over their condition with self administration and the therapy and may help lower healthcare costs and resource utilization by keeping these patients out of emergency rooms.
"The unpredictable nature of PSVT places an overwhelming burden on patients who lack effective at-home interventions to manage their episodes," said James Ip, MD, associate professor and director of cardiac pacing and implantable devices, Division of Cardiology, Weill Cornell Medicine, New York Presbyterian Hospital, the study's presenter and a RAPID investigator said in a prepared statement. "Data from the RAPID trial demonstrate that patients on the etripamil regimen had both a greater degree of conversion and a much faster conversion than those taking placebo. These findings further support that etripamil could offer patients a meaningful intervention for their condition outside of the more costly and inconvenient acute-care setting."
The multi-center, randomized, double-blind, placebo-controlled RAPID trial enrolled 706 patients across clinical sites in North America and Europe. Patients were randomized 1:1 to a nasal spray of etripamil or placebo, as prompted by symptoms of PSVT and without medical monitoring. To maximize the potential treatment effect of etripamil, patients who did not experience PSVT-symptom relief within 10 minutes were directed to self-administer a repeat dose of study drug. Pre- and post-drug ambulatory electrocardiographic (ECG) data were independently adjudicated.
The RAPID trial achieved its primary endpoint, with patients taking etripamil demonstrating a highly statistically significant and clinically meaningful difference in time to PSVT conversion compared to placebo. A Kaplan Meier analysis showed a statistically significantly greater proportion of patients who took etripamil converted within 30 minutes compared to placebo (64.3% vs. 31.2%; hazard ratio [HR] = 2.62; 95% CI 1.66, 4.15; p<0.001). By 90 minutes post-study drug administration, 80.6% of etripamil patients converted versus 60.7% of placebo patients (HR = 1.93; 95% CI 1.349, 2.752; p<0.001) and statistical significance was maintained throughout the five-hour observation window. Significant reductions in time to conversion in patients who took etripamil were evident early and persisted throughout the observation window of the study compared to placebo. The median time to conversion for patients in RAPID who received etripamil was 17.2 minutes compared to 53.3 minutes for patients on placebo.
The safety and tolerability data from the RAPID trial continue to support the potential self-administration of etripamil, with findings consistent with those observed in prior trials.
Keeping PSVT patients out of emergency rooms
In the RAPID study, patients who were treated with etripamil sought additional medical interventions less frequently (15% vs. 25%; p=0.103) and had fewer emergency department visits (14% vs. 21%; p=0.209) than patients in the placebo arm. These findings were consistent with the previously completed Phase 3 NODE-301 study, in which patients who were treated with etripamil also sought additional medical interventions less frequently (14% vs. 27%; p=0.119) and saw a reduction in emergency department visits (13% vs. 25%; p=0.076) compared to patients in the placebo arm.
FDA submission for etripamil
Results from the RAPID trial, combined with data from the NODE-301 trial, are expected to fulfill the efficacy requirement for a U.S. Food and Drug Administration (FDA) new drug application (NDA) submission for etripamil. Milestone Pharmaceuticals Inc. plans to submit an NDA application in mid-2023 pending agency feedback.
Current treatment for PSVT
PSVT affects about 2 million Americans and is characterized by intermittent episodes of a rapid heartbeat that starts and stops suddenly. Episodes of supraventricular tachycardia (SVT) are often associated with symptoms such as palpitations, sweating, chest pressure or pain, shortness of breath, sudden onset of fatigue, lightheadedness or dizziness, fainting and anxiety. Intravenous medications, including adenosine, beta-blockers and calcium channel blockers, have long been used for the acute treatment of PSVT. But these medications must be administered under medical supervision, usually in an emergency department or other acute care setting.
Many cardiologists have seen etripamil as a break-through treatment because it allows patients to treat their symptoms on their own with an easy to use nasal spray without the need for an emergency room visit and IV drug administration. When the Node-301 trial was presented at the Heart Rhythm Society (HRS) 2017 meeting, it was one of the most talked about trials presented.
Dave Fornell has covered healthcare for more than 17 years, with a focus in cardiology and radiology. Fornell is a 5-time winner of a Jesse H. Neal Award, the most prestigious editorial honors in the field of specialized journalism. The wins included best technical content, best use of social media and best COVID-19 coverage. Fornell was also a three-time Neal finalist for best range of work by a single author. He produces more than 100 editorial videos each year, most of them interviews with key opinion leaders in medicine. He also writes technical articles, covers key trends, conducts video hospital site visits, and is very involved with social media. E-mail: dfornell@innovatehealthcare.com