Milestone Pharmaceuticals Presents Positive Results from ReVeRA Phase 2 Study of Etripamil in AFib-RVR at the American Heart Association Scientific Sessions 2023
- Etripamil, an investigational drug, showed statistically significant reduction in ventricular rate by 30 beats per minute for episodes of atrial fibrillation with rapid ventricular rate (p < 0.0001) compared to placebo
- Results also showed statistically significant rapid and sustained reductions in ventricular rate and improvement in patient reported symptoms
- Safety and tolerability data were generally consistent with data from studies evaluating etripamil in PSVT
- Results support further clinical development in a Phase 3 clinical trial evaluating patient-administered etripamil for management of AFib-RVR
MONTREAL and CHARLOTTE, N.C.,
Incidence of atrial fibrillation (AFib) in
"Breakthrough episodes of rapid ventricular rate in patients with AFib are frequent and often symptomatic and may result in increasing burdens in patients' everyday lives and disruptions to the healthcare system. Today, there is an unmet need for a portable, fast-acting treatment solution that can be easily administered by patients when they experience a sudden episode," said
"The results from the ReVeRA study are promising and demonstrate the potential of etripamil nasal spray to rapidly reduce heart rate and provide symptomatic benefit to patients suffering from AFib-RVR," said
Randomized, Controlled Study of the Efficacy and Safety of Etripamil Nasal Spray: Findings from Phase 2 ReVeRA-201 Study (AHA Featured Science Session)
The randomized, controlled Phase 2 ReVeRA study treated 56 patients aged 18 years and older presenting in an emergency department or hospital with AFib with a ventricular rate of 110 or more beats per minute (bpm) prior to receiving either etripamil nasal spray or placebo. The study was designed to assess the reduction in ventricular rate (primary endpoint), the time to achieve maximum reduction in ventricular rate, the duration of effect, and patient satisfaction with treatment using the Treatment Satisfaction Questionnaire 9 (TSQM-9) patient reported outcome (PRO) tool (secondary endpoints).
Data from the ReVeRA trial showed that delivery of etripamil nasal spray significantly and rapidly reduced ventricular rate, consistent with the drug's pharmacologic profile. The study achieved its primary endpoint with high statistical significance with patients experiencing a mean ventricular rate reduction of 29.91 bpm (95% confidence interval: -40.31, -19.52; p < 0.0001) in the etripamil arm compared to placebo. The absolute maximum reduction in rate was 35 bpm in the etripamil arm, compared with 5 bpm in the placebo arm. The median time to maximum reduction in ventricular rate was 13 minutes in the etripamil arm, and time course graphs of mean ventricular rate reduction illustrate onset of etripamil within minutes after drug administration and lasting approximately 150 minutes compared to placebo.
A greater number of patients receiving etripamil achieved a ventricular rate of less than 100 bpm (58.3%) than those receiving placebo (4%). Furthermore, 67% of patients receiving etripamil achieved at least 20% reductions in ventricular rate and 96% achieved at least 10% reductions in ventricular rate in the first 60 minutes compared to 0% and 20% on placebo, respectively. Using the TSQM-9, compared to placebo, patients treated with etripamil demonstrated significant improvements in two satisfaction ratings: effectiveness (p < 0.0001) and relief of symptoms (p = 0.0002).
Serious adverse events (SAEs) occurring in the 24 hours after drug were rare, with two occurring in one patient in the etripamil arm (3.7%) and four occurring in two patients in the placebo arm (6.9%). The SAEs in the etripamil arm were transient severe bradycardia and syncope, assessed as due to hyper-vagotonia, which occurred in a patient with a history of vagal events, and fully resolved by placing the patient supine and without sequelae. The most common (≥ 5%) adverse events were mild or moderate in intensity and included nasal discomfort and congestion, rhinorrhea ("runny nose"), and dizziness.
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About Atrial Fibrillation with Rapid Ventricular Rate
An estimated five million Americans suffer from atrial fibrillation (AFib), a common arrhythmia marked by an irregular, disruptive and often rapid heartbeat. The incidence of AFib is expected to grow to approximately 10 million by 2025 and up to about 12 million by 2030.1,2,3 A subset of patients with AFib experience episodes of abnormally high heart rate most often accompanied by palpitations, shortness of breath, dizziness, and weakness. While these episodes, known as AFib-RVR, may be treated by oral calcium channel blockers and/or beta blockers, patients frequently seek acute care in the emergency department to address symptoms. In 2016, nearly 800,000 patients were admitted to the emergency department due to AFib symptoms where treatment includes medically supervised intravenous administration of calcium channel blockers or beta blockers, or electrical cardioversion. With little available data for AFib-RVR, Milestone's initial market research indicates that 30 to 40% of patients with AFib experience one or more symptomatic episodes of RVR per year that require treatment, suggesting a target addressable market of approximately three to four million patients in 2030 for etripamil in patients with AFib-RVR.
Etripamil is Milestone's lead investigational product. It is a novel calcium channel blocker nasal spray under clinical development for elevated and often highly symptomatic heart-rate attacks associated with PSVT and AFib-RVR. It is designed to be a rapid-response therapy that is self-administered by the patient, without the need for direct medical oversight. If approved, etripamil is intended to provide health care providers with a new treatment option to enable on demand care and patient self-management. If approved, the portable treatment, studied as self-administered, may provide patients with active management and a greater sense of control over their condition. CARDAMYST™, the conditionally approved brand name for etripamil nasal spray, is well studied with a robust clinical trial program that includes a completed Phase 3 clinical-stage program for the treatment of PSVT and Phase 2 proof-of-concept trial for the treatment of patients with AFib-RVR.
Milestone Pharmaceuticals Inc. (Nasdaq: MIST) is a biopharmaceutical company developing and commercializing innovative cardiovascular medicines to benefit people living with certain heart conditions. Milestone recently submitted a New Drug Application (NDA) to the
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as "believe," "continue," "could," "demonstrate," "designed," "develop," "estimate," "expect," "may," "pending," "plan," "potential," "progress," "will" and similar expressions (as well as other words or expressions referencing future events, conditions, or circumstances) are intended to identify forward-looking statements. These forward-looking statements are based on Milestone's expectations and assumptions as of the date of this press release. Each of these forward-looking statements involves risks and uncertainties. Actual results may differ materially from these forward-looking statements. Forward-looking statements contained in this press release include statements regarding the anticipated growth of incidence of AFib and AFib-RVR by 2030; the ability of etripamil to provide patients with a treatment solution that delivers significant symptom relief and helps reduce potential visits to the emergency department; the ability of etripamil nasal spray to rapidly reduce heart rate and provide symptomatic benefit to patients suffering from AFib-RVR; the continued ability of etripamil provided superior time to conversion to normal heart rhythm compared to placebo; the timing of the anticipated launch of etripamil; the success of the NDA submission for etripamil nasal spray and the timing of the
1 Colilla S, Crow A, Petkun W, Singer DE, Simon T, Liu X. Estimates of current and future incidence and prevalence of atrial fibrillation in the
2 Miyasaka Y, Barnes ME, Gersh BJ, et al. Secular trends in incidence of atrial fibrillation in
3 Benjamin, E. J., Muntner, P., et al.
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