Milestone Pharmaceuticals Inc., a Canadian biopharmaceutical firm specializing in cardiovascular therapies, recently reported positive results from a Phase III clinical trial of its leading candidate, etripamil nasal spray, for the treatment of paroxysmal supraventricular tachycardia (PSVT).
The trial results, published in The Lancet, demonstrated significant improvement in various PSVT symptoms among patients who received the nasal spray compared to those who received a placebo. This substantial achievement paves the way for Milestone Pharmaceuticals to proceed with a New Drug Application (NDA) submission in late 2023.
“Publication of these results in The Lancet, a high-impact, international journal, underscores our confidence in the potential for etripamil to deliver value to the healthcare system through a reduction in utilization of emergency- and acute-care services and, importantly, to have a meaningful impact on the patients burdened with this unpredictable and serious condition,” said David Bharucha, chief medical officer of Milestone Pharmaceuticals, in the company’s press release.
“We believe that self-administered etripamil could serve as the first approved supraventricular tachycardia treatment for use outside of the healthcare setting. We remain on track for an NDA submission in the third quarter of 2023.”
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What is Paroxysmal Supraventricular Tachycardia (PSVT)?
Paroxysmal supraventricular tachycardia (PSVT) is an arrhythmia characterized by an abnormal heart rhythm. It occurs when a rapid, short-circuit rhythm develops in the heart’s upper chamber.
Normally, the electrical impulse originates from the sinus node, a small area in the heart’s right atrium; however, in PSVT, there is an abnormal electrical activity in the atria, leading to rapid and repetitive contractions. This can potentially affect heart function.
While PSVT may not always require treatment and is typically not life-threatening, it is important to recognize its symptoms. These include a regular but rapid heartbeat ranging from 120 to 230 beats per minute, which starts and stops abruptly. Other symptoms may include palpitations, dizziness or lightheadedness, fatigue and chest pain.
The diagnosis of PSVT involves assessing the patient’s medical history and conducting tests such as a 12-lead electrocardiogram (ECG or EKG) monitoring or an electrophysiological (EP) study. These evaluations help identify abnormal heart rhythm and determine the appropriate treatment course.
Current treatment options for PSVT include the Valsalva maneuver (a technique to stimulate the vagus nerve to slow the heart rate), medications, catheter ablation or surgery to modify the abnormal pathways that transmit electrical signals in the heart. The choice of treatment depends on the individual patient and the severity of their symptoms.
If a patient experiences any symptoms associated with PSVT, it is crucial that they inform their healthcare provider. The healthcare provider can evaluate their condition and recommend the most suitable treatment approach.
How Does Etripamil Nasal Spray Work?
Etripamil is a fast-acting L-type calcium-channel blocker administered intranasally. It is currently being developed for self-administration by patients without medical supervision, specifically for the acute conversion of atrioventricular-nodal-dependent PSVT. When administered through the nasal route, etripamil is rapidly absorbed by the nasal mucosa, with peak concentration achieved within 7 minutes following a 70 mg dose. It is then efficiently metabolized by the body.
The effectiveness of etripamil was evaluated in a multi-center, randomized, double-blind, placebo-controlled clinical trial known as RAPID. This trial enrolled 706 patients from various clinical sites across North America and Europe.
The results showed that etripamil demonstrated both statistically significant and clinically meaningful differences compared to placebo. Approximately 64.3 percent of patients who self-administered etripamil experienced a conversion from PSVT to normal sinus rhythm within 30 minutes, in contrast to 31.2 percent of patients on placebo. Additionally, the time to conversion was significantly reduced in the etripamil group (17.2 minutes) compared to the placebo group (53.5 minutes).
The data also indicated a statistically significant improvement in multiple defined symptoms of PSVT among patients treated with etripamil compared to those receiving the placebo. Moreover, patients treated with etripamil showed a reduction in emergency department visits and a decreased need for intravenous treatments.
The clinical study further demonstrated the favorable tolerability profile of etripamil, reinforcing its potential as a viable long-term treatment option. The most frequently observed randomized treatment-emergent adverse events (RTEAEs), which are adverse events (AEs) occurring within 24 hours of administering the study drug, were primarily associated with the nasal administration site. Overall, the majority of RTEAEs were reported as mild (68 percent) or moderate (31 perceent). Importantly, no serious AEs related to etripamil were reported during the study.
“With patients experiencing PSVT on the etripamil regimen having a much faster and greater degree of conversion to sinus rhythm compared to placebo, these results from the RAPID trial strongly support the potential for etripamil to offer patients a rapid, effective and safe at-home intervention to manage their episodes whenever they occur,” said Bruce Stambler, lead author, Piedmont Heart Institute, Atlanta, GA, in the news release.
Alternative Treatments for PSVT
There are several drugs that are approved by the US Food and Drug Administration (FDA) for the treatment of PSVT. One such drug is Adenosine, which was initially approved by the FDA in 1989. It is used to treat PSVT, including cases associated with accessory bypass tracts like Wolff-Parkinson-White syndrome. Adenosine is typically administered through a rapid intravenous (IV) bolus injection into a vein or an IV line and requires a prescription.
Another prescribed drug for PSVT is Verapamil, a calcium antagonist or slow-channel inhibitor. It received FDA approval in 1998. Verapamil is indicated for various conditions including angina (chronic stable, vasospastic or Prinzmetal variant), unstable angina (crescendo, preinfarction), hypertension as add-on therapy, PSVT and supraventricular tachycardia (SVT).