Impel NeuroPharma (NASDAQ: IMPL), a late-stage biopharmaceutical
company focused on the development and commercialization of
transformative therapies for patients living with central nervous
system (CNS) diseases who have high unmet medical needs, announced
today that its pivotal Phase 3, open-label study, STOP 301, was
published in the August 7, 2021 edition of Headache: The Journal of
Head and Face Pain, the official journal of the American Headache
Society. TRUDHESA™ (INP104) is dihydroergotamine mesylate (DHE)
delivered directly into the vascular-rich upper nasal space using
Impel’s proprietary Precision Olfactory Delivery (POD®) technology
for the treatment of acute migraine.
“We are proud to announce the publication of our
pivotal data, which further reinforce the potential for TRUDHESA to
be a differentiated, well-tolerated treatment that, subject to
approval by the FDA, has the potential to deliver rapid and
reliable symptom relief for patients with acute migraine,” said
Stephen Shrewsbury, M.D., Chief Medical Officer at Impel
NeuroPharma. “We were particularly pleased to see that most
patients reported that TRUDHESA was easy to use, and allowed them
to return to normal activities of daily living faster compared with
their previous treatment.”
The publication, which can be found here,
addresses the STOP 301 trial, which is an open-label study with the
primary objective of assessing the long-term safety and
tolerability of TRUDHESA in the acute treatment of migraine, with a
specific focus on nasal mucosa and olfactory function. Exploratory
objectives included efficacy assessments of migraine measures and a
patient acceptability questionnaire.
“I am pleased to see pivotal data demonstrating
that INP104 was both safe and tolerable with long-term use. This is
welcome and important news to people living with migraine who have
experienced inadequate relief with existing therapies and the
physicians who treat them who are in need of new options,” said Tim
Smith, M.D., RPh, FACP, AQH, First Vice President, The National
Headache Foundation, STOP 301 Principal Investigator and lead
author of the publication. “Right now, there is a critical need for
non-oral treatment options in particular because many patients
living with migraine also have related gastrointestinal disorders
and are often unable to achieve relief with oral routes of
administration.”
The New Drug Application (NDA) for INP104 was
accepted for review by the U.S. Food and Drug Administration (FDA)
in January 2021 and has a Prescription Drug User Fee Act (PDUFA)
target action date of September 6, 2021. The FDA has conditionally
accepted a trade name of TRUDHESA.
If approved by the FDA, TRUDHESA will become the
first and only therapy to deliver DHE to the vascular-rich upper
nasal space using the POD technology, a novel delivery system. Many
current nasal delivery technologies – sprays, droppers, and pumps –
may deliver less than five percent of the active drug to the upper
nasal space.1
About STOP 301: 2 STOP 301 is a
pivotal Phase 3 open-label study that evaluated the safety,
tolerability, exploratory efficacy, and patient acceptability of
INP104 (TRUDHESA™). After a 28-day screening period—where patients
kept a daily diary and were being treated with their established
‘best’ usual care—patients were given TRUDHESA to treat
self-recognized migraine attacks.
The trial enrolled 360 patients at 36 sites in
the United States who had a documented diagnosis of migraine with
or without aura, with at least two attacks per month for the
previous six months. In the trial, 354 patients received at least
one dose of TRUDHESA and comprised the 24-week Full Safety Set. The
Primary Safety Set was comprised of 185 patients who took an
average of two or more treatments with TRUDHESA per 28-day period
during the 24-week treatment period. During the 24-week study,
4,515 self-reported migraine attacks were treated with TRUDHESA.
The study evaluated 6,332 doses of TRUDHESA over the full 52
weeks.
In the study, TRUDHESA exhibited a
well-tolerated safety profile throughout the initial 24-week
treatment period and the full 52-week treatment period, with no
serious adverse events (AEs) related to study treatment reported.
TRUDHESA-related treatment-emergent AEs were reported by 36.7
percent of patients, and 6.8 percent discontinued treatment due to
AEs over 24 weeks. No new safety signals, including cardiovascular
(CV) safety signals, were observed following treatment, though
patients with a history of CV disease were excluded from the study.
A Nasal Safety Review Committee reviewed the nasal safety data and
suggested TRUDHESA may be safe and tolerable on the nasal mucosa.
In addition, nausea—which is typically observed in intravenous (IV)
formulations of DHE—was reported by 6.8 percent of patients.
The study also assessed patient-reported
exploratory efficacy using patients’ best usual care at baseline
compared to TRUDHESA-treated attacks over 24 and 52 weeks. Pain
freedom, the most bothersome symptom freedom, and pain relief at 2
hours post-TRUDHESA were self-reported in an eDiary, with almost
half of patients reporting pain relief at one hour following INP104
administration, and efficacy of TRUDHESA was similar if patients
administered within 2 hours of migraine initiation or beyond. A low
recurrence rate at 24 and 48 hours was also observed. Furthermore,
there was a low rate of treatment discontinuation, with 74 percent
of patients completing the 24-week period. Of those who completed
24 weeks, 73 entered the 28-week extension, and of those, 90.4
percent completed the study. The study found that 98 percent of
patients with pain freedom had sustained pain freedom through 24
hours and 95 percent through 48 hours. Additionally, of the 38
percent of patients who self-reported two-hour pain freedom for
their first TRUDHESA-treated attack, only 7.1 percent and 14.3
percent of patients self-reported recurrence of migraine at 24 and
48 hours post- TRUDHESA administration, respectively.
Exploratory endpoints included a patient
acceptability questionnaire (PAQ) assessing the patient's
impression of TRUDHESA usability and effectiveness. Most patients
reported TRUDHESA was easy to use, and patients also reported
faster and more consistent onset of effect with TRUDHESA than with
their previous best usual care treatment. Compared with their
previous treatment, the majority of patients reported that TRUDHESA
kept their migraine from coming back for a longer time and allowed
them to return to normal activities of daily living faster.
About Precision Olfactory Delivery
Technology:Impel’s proprietary Precision Olfactory
Delivery (POD®) technology is able to deliver a range of
therapeutic molecules and formulations into the vascular-rich upper
nasal space, believed to be a gateway for unlocking the previously
unrealized full potential of these molecules. By delivering
predictable doses of drug directly to the upper nasal space,
Impel’s precision performance technology has the goal of enabling
increased and consistent absorption of drug, overriding the high
variability associated with other nasal delivery systems, yet
without the need for an injection. While an ideal target for drug
administration, to date no technology has been able to consistently
deliver drugs to the upper nasal space. By utilizing this route of
administration, Impel NeuroPharma has been able to demonstrate
blood concentration levels for its investigational therapies that
are comparable to intramuscular (IM) administration and can even
reach intravenous (IV)-like systemic levels quickly, which could
transform the treatment landscape for CNS and other disorders.
Importantly, the POD technology offers propellant-enabled delivery
of dry powder and liquid formulations that eliminates the need for
coordination of breathing, allowing for self- or
caregiver-administration in a manner that may improve patient
outcome, comfort, and potentially, compliance.
About Migraine and About the Acute
Treatment of Migraine:Migraine is a common and
debilitating neurological disease characterized by recurrent
episodes of severe head pain and associated with nausea, vomiting
and sensitivity to light and sound.3 Migraine affects
approximately 36 million people in the United States.4 Of the
approximately 18 million diagnosed migraine patients, only four
million are on prescription treatment.5 While triptans account
for almost 80 percent of migraine therapies, approximately 30 to 40
percent of patients do not respond adequately to triptans and up to
79 percent of the patients who do respond to triptans report being
dissatisfied with their current treatment and willing to try a new
therapy.6,7,8 Further, evidence suggests that gastroparesis,
delayed emptying of the stomach, is a prevalent feature in migraine
that may delay or reduce the absorption of oral medications,
including triptans, gepants and ditans. This means that acute
medications can remain in the stomach for hours, delaying symptom
relief, leading to loss of confidence (about future administration)
and prolonged suffering for the current migraine attack.9
About TRUDHESA™:Impel
NeuroPharma is developing TRUDHESA with the goal to be a
transformative new therapy for the acute treatment of migraine
headaches. TRUDHESA aims to optimize dihydroergotamine mesylate
(DHE) for fast and lasting whole migraine relief, regardless of
when in the migraine attack it is administered, without an
injection. Importantly, TRUDHESA is designed to deliver a lower
dose of DHE compared to other nasally administered, FDA-approved
and investigational products. This may enable patients to benefit
from the established efficacy of DHE, without the undesired side
effects that may be experienced with delivery to the lower nasal
space.
TRUDHESA utilizes Impel’s propellant-enabled POD
technology to conveniently and consistently deliver optimal doses
of DHE deep into the vascular rich upper nasal space, an ideal
target for efficient drug administration. This may be particularly
important for the majority of patients with migraine who experience
nausea and/or vomiting during an attack, which presents limitations
for the use of oral therapies, including triptans, CGRP inhibitors
and ditans as well as other non-specific medications used for the
acute treatment of migraine.
About Impel NeuroPharma:Impel
NeuroPharma, Inc. is a late-stage pharmaceutical company focused on
utilizing its proprietary technology to develop and commercialize
transformative therapies for people suffering from diseases with
high unmet needs, with an initial focus on diseases of the CNS. The
Company’s strategy is to rapidly advance its product candidate
pipeline that pairs its proprietary Precision Olfactory Delivery
(POD®) system with well-established therapeutics, including INP104
for the acute treatment of migraine, INP105 for the acute treatment
of agitation in patients with autism, and INP107 for OFF episodes
in Parkinson’s disease.
Cautionary Note on Forward-Looking
StatementsThis press release contains “forward-looking”
statements within the meaning of the safe harbor provisions of the
U.S. Private Securities Litigation Reform Act of 1995, including,
but not limited to, timing of approval of Impel’s NDA for INP104
(proposed trade name TRUDHESA™) and of Impel’s other regulatory
submissions, timing of announcements of clinical results and
clinical development activities of its product candidates,
potential benefits and market opportunities of INP104 and its other
product candidates and its cash runway. Forward-looking statements
can be identified by words such as: “believe,” “may,” “will,”
“potentially,” “estimate,” “continue,” “anticipate,” “intend,”
“could,” “would,” “project,” “plan,” “expect” or the negative or
plural of these words or similar expressions. These statements are
subject to numerous risks and uncertainties that could cause actual
results and events to differ materially from those anticipated,
including but not limited to, Impel’s ability to obtain and
maintain regulatory approval of INP104 and its other product
candidates, its ability to execute its commercialization strategy
for INP104 its ability to develop, manufacture and commercialize
its product candidates including plans for future development of
its POD devices and plans to address additional indications for
which Impel may pursue regulatory approval, whether results of
preclinical studies or clinical trials will be indicative of the
results of future trials, and the effects of COVID-19 on its
clinical programs and business operations. Many of these risks are
described in greater detail in Impel’s filings with the Securities
and Exchange Commission. Any forward-looking statements in this
press release speak only as of the date of this press release.
Impel assumes no obligation to update forward-looking statements
whether as a result of new information, future events or otherwise,
after the date of this press release.
Impel, POD and the Impel logo are trademarks of
Impel NeuroPharma, Inc. To learn more about Impel NeuroPharma,
please visit our website at https://impelnp.com/.
Contact:Lance BuckleyLippe Taylor
Grouplbuckley@lippetaylor.com917-439-2241
________________________
1 Silberstein SD, et al. Headache. 2020;60:p 47/col 2/para 1.2
Data on File.3 Mayo Clinic. Migraine Symptoms & Causes. Last
Accessed February 3, 20204 Migraine Research Foundation. Migraine
Facts. Last Accessed February 3, 20205 Data on File.6 Smitherman
TA, Burch R, et al. The prevalence, impact, and treatment of
migraine and severe headaches in the United States: a review of
statistics from national surveillance studies. Headache. 2013
Mar;53(3):427-367 Leroux E, Buchanan A, et al. Evaluation of
patients with insufficient efficacy and/or tolerability to triptans
for the acute treatment of migraine: A systematic literature
review. Adv Ther. 2020 Dec;37(12):4765-4796.8 Bigal M, Rapoport A,
et al. Satisfaction with current migraine therapy: experience from
3 centers in US and Sweden. Headache. 2007 Apr;47(4):475-99 Aurora
S, et al. Cephalalgia. 2013; 33:408-415; Tokola RA et al. Br J Clin
Pharmacol. 1984. 18:867-871; Volans GN. Clin Pharmacokinet. 1978
3:313-318
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