- Primary
endpoint met, with 64.3% of patients who self-administered
etripamil converting from supraventricular tachycardia to sinus
rhythm within 30 minutes compared to 31.2% on placebo (HR = 2.62,
p<0.001)
- Significant
improvement in multiple symptoms of supraventricular
tachycardia in patients receiving etripamil compared to
placebo
- Safety and
tolerability profile of repeat-dose regimen consistent with
previously studied single-dose self-administration and supportive
of NDA submission
- NDA submission
for etripamil in patients with PSVT on track for 3Q23
MONTREAL and CHARLOTTE, N.C., June 20, 2023 /CNW/ -- Milestone
Pharmaceuticals Inc. (Nasdaq: MIST), a biopharmaceutical
company focused on the development and commercialization of
innovative cardiovascular medicines, today announced the
publication of results in The Lancet from the Phase 3
RAPID clinical trial evaluating etripamil nasal spray, the
Company's investigational calcium channel blocker, in patients with
paroxysmal supraventricular tachycardia (PSVT).
"PSVT places a significant burden on both patients and the
healthcare system, with currently available acute therapies often
marked by low effectiveness or undesirable side effects, and
limited to the costly and inconvenient acute-care setting," said
Bruce Stambler, M.D., Lead Author,
Piedmont Heart Institute, Atlanta,
GA. "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."
"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,
M.D., Ph.D., F.A.C.C., Chief Medical Officer of Milestone
Pharmaceuticals. "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."
The publication, titled "Self-administered Intranasal
Etripamil Using a Symptom-Prompted, Repeat-Dose Regimen for
Atrioventricular-Nodal Dependent Supraventricular Tachycardia: The
Randomised, Controlled RAPID Trial," is available via the
following link:
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)00776-6/fulltext.
Phase 3 RAPID Trial
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
self-administer a nasal spray of etripamil or placebo, as prompted
by symptoms of PSVT, without medical monitoring and when an episode
occurred in the course of daily activities. 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 in this event-driven trial.
Key findings from the trial featured in the publication, which
support the potential self-administration of etripamil outside of
the healthcare setting, are summarized below:
- The RAPID trial achieved its primary endpoint, with patients
taking etripamil demonstrating a highly statistically
significant and clinically meaningful difference in time to
supraventricular tachycardia conversion compared to placebo. A
Kaplan Meier analysis showed a
statistically significantly greater proportion of patients who took
etripamil converted within thirty minutes compared to placebo
(64.3% vs. 31.2%; hazard ratio [HR] = 2.62; 95% CI 1.66, 4.15;
p<0.001).
- Significant reductions in time to conversion in patients who
took etripamil were evident early and were durable,
persisting throughout the observation window of the study compared
to placebo, with a median time to conversion of 17.2 minutes
(95% CI= 13·4, 26·5) for patients treated with
etripamil versus 53.5 minutes (95% CI= 38.7,
87.3) for patients treated with placebo.
- Data demonstrated statistically significant improvement in
multiple defined symptoms of PSVT in patients
receiving etripamil compared to placebo, using a
patient-reported outcome (PRO) questionnaire.
- Reduction in emergency-department visits and, for example, need
for intravenous treatments, was observed, though not with
statistical significance in this dataset alone.
- 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. The
most common randomized treatment emergent adverse events
(RTEAEs), which are adverse events (AEs)
that occurred within 24 hours of study drug administration, were
related to the nasal administration site. Overall, the majority
of RTEAEs were reported as mild (68%) to moderate
(31%). There were no reported serious AEs related
to etripamil.
As previously communicated, Milestone plans to submit a New Drug
Application (NDA) filing in the third quarter of 2023.
About Paroxysmal Supraventricular Tachycardia
Paroxysmal Supraventricular Tachycardia (PSVT) is a highly
symptomatic and impactful heart arrhythmia characterized by
unpredictable attacks of a racing heart that afflicts approximately
two million Americans. Symptoms of PSVT, including palpitations,
chest pressure, and shortness of breath are often debilitating,
causing the patient to stop their current activities or avoid
pursuits altogether. The impact and morbidity from an attack can be
especially detrimental in patients with underlying cardiovascular
or medical conditions, such as heart failure, obstructive coronary
disease, or dehydration. The uncertainty of when an episode of SVT
will strike or how long it will persist can provoke anxiety in
patients, which can have a negative impact on their day-to-day
life. Many doctors are unsatisfied by the lack of effective
treatment options besides a prolonged, unpleasant, and costly trip
to the emergency department or, for some patients, an invasive
ablation procedure.
About Etripamil
Etripamil, Milestone's lead investigational product, is a novel
calcium channel blocker nasal spray. It is designed to be a
rapid-response therapy that is self-administered by the patient,
without the need for direct medical oversight, and is being
developed for elevated and often highly symptomatic heart rate
attacks associated with PSVT and AFib-RVR. If approved, etripamil
is intended to provide health care providers with a new tool to
enable virtual care and patient self-management, and to impart upon
the patient a greater sense of control over their condition.
Milestone is conducting a comprehensive development program for
etripamil, with Phase 3 trials completed and an NDA soon to be
submitted in the third quarter of 2023 in paroxysmal
supraventricular tachycardia (PSVT). Milestone also has a Phase 2
proof-of-concept trial that is ongoing in patients experiencing
atrial fibrillation with rapid ventricular rate (AFib-RVR).
About Milestone Pharmaceuticals
Milestone Pharmaceuticals Inc. (Nasdaq: MIST) is a
biopharmaceutical company focused on the development and
commercialization of innovative cardiovascular medicines.
Milestone's lead product candidate etripamil recently completed its
Phase 3 clinical-stage program for the treatment of paroxysmal
supraventricular tachycardia (PSVT) and is in a Phase 2
proof-of-concept trial for the treatment of patients with atrial
fibrillation with rapid ventricular rate (AFib-RVR). Milestone
Pharmaceuticals operates
in Canada and the United States. For more
information, visit www.milestonepharma.com and follow
Milestone on Twitter at @MilestonePharma.
Forward-Looking Statements
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 potential of etripamil to serve as a promising
therapy for PSVT patients; the potential for self-administered
etripamil to serve as the first approved supraventricular
tachycardia treatment for use outside of the healthcare
setting; the timing of the NDA submission for etripamil nasal
spray; and further clinical development of etripamil and continued
success with future clinical trials. Important factors that could
cause actual results to differ materially from those in the
forward-looking statements include, but are not limited to, the
risks inherent in biopharmaceutical product development and
clinical trials, including the lengthy and uncertain regulatory
approval process; uncertainties related to the timing of
initiation, enrollment, completion, evaluation and results of our
clinical trials; risks and uncertainty related to the complexity
inherent in cleaning, verifying and analyzing trial data; and
whether the clinical trials will validate the safety and efficacy
of etripamil for PSVT or other indications, among others, general
economic, political, and market conditions, including deteriorating
market conditions due to investor concerns regarding inflation and
Russian hostilities in Ukraine and overall fluctuations
in the financial markets in the United States and abroad,
risks related to pandemics and public health emergencies, and risks
related the sufficiency of Milestone's capital resources and its
ability to raise additional capital in the current economic
climate. These and other risks are set forth in Milestone's filings
with the U.S. Securities and Exchange Commission, including in
its annual report on Form 10-K for the year ended December 31,
2022 and its quarterly report on Form 10-Q for the quarter ended
March 31, 2023, in each case under
the caption "Risk Factors," as such discussion may be updated from
time to time by subsequent filings it may make with the U.S.
Securities & Exchange Commission. Except as required by law,
Milestone assumes no obligation to update any forward-looking
statements contained herein to reflect any change in expectations,
even as new information becomes available.
Contact
David Pitts
Argot Partners
212-600-1902
milestone@argotpartners.com
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SOURCE Milestone Pharmaceuticals, Inc.