– Study missed primary endpoint of mean time to
conversion of SVT to SR over a five-hour period following dosing
(p=0.12) –
– Etripamil showed rapid conversion of SVT to SR during
the first 45 minutes (p=0.02), consistent with its known
pharmacology –
– Study demonstrated a positive safety profile showing
etripamil was well tolerated in the at-home setting –
– Small number of placebo patients and prolonged
efficacy measurement period confounded results –
– Company plans to discuss next steps with regulators
and continue its full PSVT clinical program, including NODE-301B,
NODE-302 and NODE-303 –
– Company to host conference call today at 5:00 p.m. ET –
MONTREAL and CHARLOTTE, N.C., March
23, 2020 /CNW/ -- Milestone Pharmaceuticals Inc. (Nasdaq:
MIST), a biopharmaceutical company focused on the development and
commercialization of innovative cardiovascular medicines, today
announced topline results from its Phase 3, multicenter,
randomized, double-blind, placebo-controlled NODE-301 trial of its
investigational new drug, etripamil nasal spray, the Company's
novel short-acting calcium channel blocker, in patients with
paroxysmal supraventricular tachycardia (PSVT).
The NODE-301 trial, which enrolled a total of 431 patients
across 65 sites in the U.S. and Canada, is an event-driven Phase 3
efficacy trial of etripamil for terminating supraventricular
tachycardia (SVT) episodes in the at-home setting. Etripamil
(70mg) did not achieve its primary endpoint of time to conversion
of SVT to sinus rhythm (SR) compared to placebo over the five hour
period following study drug administration (median time to
conversion of 25 minutes [95% CI: 16, 43] for etripamil vs. 50
minutes [95% CI: 31,101] for placebo, p=0.12). Despite early
activity, including the conversion of 61% of etripamil patients vs.
45% of placebo patients by 45 minutes (p=0.02), a time period
consistent with etripamil's known pharmacological activity, results
from the latter part of the analysis confounded the statistical
analysis of the primary endpoint.
The study demonstrated statistically significant
improvements in favor of etripamil over placebo in the important
secondary endpoint of patient reported treatment satisfaction, as
measured by a treatment satisfaction questionnaire for medication
(TSQM-9), including global satisfaction (p=0.0069) and
effectiveness scores (p=0.0015), with questions addressing the
relief of symptoms commonly associated with an episode of SVT, such
as rapid pulse, heart palpitations, anxiety, shortness of breath
and dizziness. Additionally, there was a trend in improvement in
the percentage of patients seeking rescue medical intervention,
including in the emergency department, with etripamil and placebo
patients reporting 15% and 27%, respectively (p=0.12).
The safety and tolerability data from the NODE-301 study are
supportive of at-home use of etripamil, with adverse events (AE)
consistent with those observed in prior trials. The most common AEs
observed in patients receiving etripamil were local to the nose,
including nasal irritation and congestion, and these events were
typically transient in nature and most commonly characterized by
the patient as mild in severity. There were no significant
differences in incidences of severe adverse events or adverse
events of interest, such as atrioventricular nodal blocks or blood
pressure-related symptoms, across the etripamil and placebo
groups.
NODE-301B, which was designed to collect double-blind data from
randomized patients who had not yet experienced an event after the
NODE-301 trial reached its target number of adjudicated SVT events,
continues. These data will be analyzed separately as a second data
set. In addition, open-label safety studies of etripamil in
subjects with PSVT, NODE-302 and NODE-303, are ongoing with active
recruitment underway. The Company is actively monitoring the
potential impact of the COVID-19 pandemic on its ongoing trials and
will provide updates on any delayed timelines or cost impacts in
the future. The Company expects to request a meeting with
regulators to discuss the NODE-301 results and its ongoing
studies.
"Efficacy signals across the earlier time points in NODE-301, in
both primary and secondary endpoints, correlate directly with our
understanding of the drug's known pharmacologic activity. We are
also encouraged to see very good safety and tolerability across the
broad population enrolled in this study. That said, outcomes after
100 minutes, which were affected by a very small number of placebo
patients remaining in the study at that time, suggest that the
design and analysis plan used in NODE-301 negatively impacted the
study's outcome," said Joseph
Oliveto, President and Chief Executive Officer of Milestone
Pharmaceuticals. "The overall results of the study reinforce our
understanding of the promising profile of etripamil and
meaningfully inform us how best to prove its efficacy moving
forward."
Mr. Oliveto added: "We will continue to execute as prudently
possible on the ongoing NODE studies, including NODE-301B, and look
forward to reviewing these data with regulators. The ongoing
pandemic highlights the need for, and strengthens our commitment
to, home use therapies."
"PSVT places a significant burden on patients and the healthcare
system, and a fast-acting therapy to resolve its symptoms when and
where episodes occur would have a material impact on both," said
Bruce Stambler, MD, FHRS, Piedmont
Heart Institute, Atlanta, GA.
"NODE-301 is a first-of-its-kind study, and as such
encountered a number of challenges relative to studying SVT
episodes outside of a controlled electrophysiology laboratory
environment. The safety results support at-home use and the
multiple efficacy signals show us that, with a confirmatory study,
etripamil could fulfill the promise of delivering a fast-acting,
patient administered therapy for PSVT."
Conference Call and Webcast
Milestone will host a conference call and webcast to discuss the
results of the NODE-301 trial today, March
23, 2020 at 5:00 p.m. ET. To
access the live call by phone, dial (800) 529-3311 (domestic) or
(470) 495-9164 (international); the conference ID is 6152207. A
live audio webcast of the event may also be accessed through the
"Investors" section of Milestone's website at
www.milestonepharma.com. A replay of the webcast will be available
for 30 days following the event.
About NODE-301
The NODE-301 trial is a Phase 3, multicenter, randomized,
double-blind, placebo-controlled trial of etripamil, the Company's
lead investigational product. Etripamil is a novel calcium channel
blocker in the form of a nasal spray, intended for the acute
treatment of PSVT and other episodic cardiovascular conditions
wherever they occur. The study is designed for a population of
those PSVT patients who historically experience 20 minutes or
longer SVT episodes or episodes requiring termination in the
emergency department. Following an in-office test dose of
etripamil, 97.5% of patients were randomized (2:1) to receive
either 70 mg of etripamil or placebo. Upon onset of PSVT symptoms,
patients applied a wireless cardiac monitor to their chest to
record heart rhythm, performed a vagal maneuver, and, if symptoms
persisted, administered study drug. Of the 198 patient-reported
events for which study drug was administered, a total of 156 were
confirmed to be SVT events by a central independent adjudication
committee and used to assess the study's efficacy endpoints.
The primary endpoint of the NODE-301 study is time to conversion
of an SVT episode to sinus rhythm after the administration of study
drug, as confirmed by a central independent adjudication committee.
Secondary study endpoints include relief of symptoms commonly
associated with an episode of SVT such as heart palpitations, chest
pain, anxiety, shortness of breath, dizziness, or fainting, and
rating of treatment satisfaction questionnaire for medication
(TSQM).
About Paroxysmal Supraventricular Tachycardia
Paroxysmal supraventricular tachycardia (PSVT) is a rapid heart
rate condition characterized by intermittent episodes of
supraventricular tachycardia (SVT) that start and stop suddenly and
without warning. Episodes of SVT are often associated with symptoms
including palpitations, sweating, chest pressure or pain, shortness
of breath, sudden onset of fatigue, lightheadedness or dizziness,
fainting, and anxiety. Certain calcium channel blockers have long
been approved for the treatment of PSVT as well as other cardiac
conditions; however, when calcium channel blockers are used for the
termination of SVT episodes, they must be administered
intravenously under medical supervision, usually in an emergency
department or other acute care setting.
About Etripamil
Etripamil, the Company's lead investigational product, is
designed to be a rapid response therapy for episodic cardiovascular
conditions. The novel calcium channel blocker is self-administered
via a nasal spray which may shift the current treatment paradigm
for many patients with PSVT from the emergency department to the
at-home setting. Milestone is conducting a comprehensive
development program for etripamil, with Phase 3 trials underway in
PSVT, and plans to commence a Phase 2 proof-of-concept trial in
atrial fibrillation patients with rapid ventricular rate, with
subsequent studies expected in other conditions where calcium
channel blockers are used.
About Milestone Pharmaceuticals
Milestone Pharmaceuticals is a biopharmaceutical company focused
on the development and commercialization of innovative
cardiovascular medicines. Milestone Pharmaceuticals operates in
Canada and the United States. For more information, visit
www.milestonepharma.com and follow the Company 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 "may," "will," "expect," "plan," "anticipate,"
"estimate," "intend" 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 (i)
the design, progress, timing, scope and results of clinical trials,
(ii) potential interactions with regulators, and (iii) the
possibility that data will support future development.
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 and evaluation of
clinical trials, and whether the clinical trials will validate the
safety and efficacy of etripamil for PSVT or other indications,
among others, as well as risks related to pandemics and public
health emergencies, including those related to COVID-19, and
risks related the sufficiency of our capital resources and our
ability to raise additional capital. 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, 2019, under
the caption "Risk Factors." 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
david@argotpartners.com
View original content to download
multimedia:http://www.prnewswire.com/news-releases/milestone-pharmaceuticals-announces-topline-results-from-first-of-its-kind-phase-3-node-301-trial-of-etripamil-for-at-home-acute-psvt-treatment-301028371.html
SOURCE Milestone Pharmaceuticals, Inc.