Announced by Milestone Pharmaceuticals on October 24, 2023, the New Drug Application includes positive results on etripamil from the pivotal phase 3 RAPID trial.
Milestone Pharmaceuticals has announced the submission of a New Drug Application (NDA) to the US Food and Drug Administration (FDA) for etripamil nasal spray for the treatment of paroxysmal supraventricular tachycardia (PSVT).1
Announced on October 24, 2023, the NDA’s comprehensive data package includes positive results from the pivotal phase 3 RAPID trial, demonstrating etripamil provided superior time to conversion to normal heart rhythm compared to placebo in patients with PSVT.
The FDA has a 60-day filing review period to determine whether the NDA is complete and accepted for review. Pending acceptance, Milestone Pharmaceuticals expects a standard 10-month review period of the NDA. The company will continue to pursue commercial preparations to support the launch of etripamil nasal spray, with the proposed trade name CARDAMYST™.
“With this submission, we are one step closer to getting etripamil into the hands of patients who are seeking a new treatment option that will allow them to take an active role in managing their PSVT,” said Joseph Oliveto, the president and chief executive officer of Milestone Pharmaceuticals.1
Approximately 2 million people in the US are currently diagnosed with PSVT, a type of arrhythmia characterized by episodes of rapid heartbeats, often exceeding 150 to 200 beats per minute. Presentation of the arrhythmia can include the sudden occurrence of episodes and extremely rapid heart rate, often spiking unpredictably during a PSVT episode.
Given the uncertainty of when an episode of PSVT will strike, it can provoke anxiety in patients between episodes, with a particularly detrimental impact on patients with underlying cardiovascular or medical comorbidities. There are currently no medications FDA-approved for acute termination of PSVT without direct medical supervision.
Etripamil is a novel calcium channel blocker nasal spray being developed for elevated and often highly symptomatic heart-rate attacks associated with PSVT and atrial fibrillation with a rapid ventricular rate (AFib-RVR). The rapid-response therapy is designed to be self-administered by a patient, without the need for direct medical oversight. Pending its approval, the portable treatment could provide patients with greater management and control over their condition.
The agent has been well-studied in a robust clinical trial program, including the completed phase 3 RAPID trial for the treatment of PSVT and the not yet reported phase 2 proof-of-concept trial for the treatment of patients with Afib-RVR.
RAPID, a global, randomized, double-blind, phase 3 clinical trial, was designed to evaluate the safety and efficacy of self-administered etripamil versus placebo in PSVT treatment.2 The primary endpoint was achieved in RAPID, with 64% of patients who self-administered etripamil converting from supraventricular tachycardia (SVT) to sinus rhythm within 30 minutes, compared to 31% on placebo (hazard ratio [HR], 2.62; P <.001). At the 1-hour mark, a benefit was observed in 73% of patients.
The results also found the significant reductions in time to conversion in patients who took etripamil were obvious early and durable, with a median time to conversion of 17 minutes (95% CI, 13.4 - 26.5) for those treated with etripamil. In contrast, those treated with placebo had a mean time to conversion of 54 minutes (95% CI, 38.7 - 87.3).
Findings from a patient-reported outcome questionnaire indicated statistically significant improvement in several defined symptoms of PSVT in patients treated with etripamil, compared to placebo. Overall, Milestone considered the safety and tolerability profile of etripamil in RAPID supportive of the NDA submission.1
“With the achievement of our first NDA submission, we want to thank the investigators, clinical trial teams, our colleagues, and, most importantly, patients whose contributions were critical to completing our registration trials,” Oliveto said.1