Impel Pharmaceuticals (NASDAQ: IMPL), a commercial-stage
pharmaceutical company developing transformative therapies for
people suffering from diseases with high unmet medical needs, today
presented results from the first-ever pharmacokinetic (PK) and
pharmacodynamic (PD) evaluation of potential drug-drug interactions
(DDIs) between Trudhesa® (dihydroergotamine [DHE] mesylate) nasal
spray (0.725 mg per spray) and orally administered gepant
medications.
The analysis being presented suggests that no
DDIs of clinical concern are theoretically predicted if Trudhesa
and gepants are co-administered within recommended clinical doses.
The study authors believe that the PD profiles of DHE and gepants
are not anticipated to overlap significantly given their differing
mechanisms of action, though potential PD DDIs cannot be completely
excluded. Additionally, while first-pass metabolism may limit the
bioavailability of orally administered drugs, since Trudhesa is
administered via the upper nasal space, it bypasses the
gastrointestinal (GI) and hepatic first-pass metabolism. These
differing routes of administration may further reduce the potential
for interaction.
“Fortunately, more recently FDA-approved
treatments have greatly expanded the tools available to clinicians
and their patients in forming a comprehensive migraine treatment
strategy,” said Nada Hindiyeh, M.D., FAHS, Director of Headache
Medicine, Metrodora Institute. “These data suggest that Trudhesa
used with some oral CGRP (calcitonin gene-related peptide) acute
medications may be a safe option that warrants further study. This
is particularly important for people with migraine who have related
GI disorders and are often unable to achieve relief with oral
routes of administration, as well as for those who don’t respond to
other treatments.”
An additional analysis from the pivotal, Phase 3
STOP 301 trial found that concomitant use of Trudhesa and erenumab,
a preventive CGRP-based therapy, is well tolerated with the
majority of adverse events being mild or moderate and considered
unrelated to treatment. Meanwhile, another analysis in a small
population found that no significant safety concerns emerged
consequent to off-protocol concomitant use of triptans and Trudhesa
during the STOP 301 trial.
“We have previously shared data supporting the
benefits of Trudhesa as a safe and effective treatment that
provides rapid and sustained relief and, importantly, can be taken
at any time within a migraine attack. These analyses shed some
light on the potential safety profile of Trudhesa when prescribed
concomitantly with certain other widely used migraine
therapeutics,” said Sheena Aurora, M.D., Vice President Medical
Affairs, Impel Pharmaceuticals. “Cumulatively, the data we’ve
shared showcase Trudhesa’s potential to address unmet needs for
patients who may have lack of efficacy with the oral gepants by
providing a reliable option that can be used for headaches
accompanied by nausea and/or vomiting and multiple types of
difficult-to-treat migraines. The unique mechanism administering
DHE to the upper nasal space further stands to position Trudhesa as
a valuable resource for effective migraine relief.”
Trudhesa uses Impel’s proprietary Precision
Olfactory Delivery (POD®) technology and is the first and only
migraine nasal spray which delivers DHE – a proven,
well-established migraine therapeutic – quickly to the bloodstream
through the vascular-rich upper nasal space. Trudhesa bypasses the
gut and reduces potential absorption issues, offering rapid,
sustained, and consistent symptom relief without nausea commonly
associated with injection or infusion DHE – even when administered
hours after the onset of a migraine attack.
About STOP 301The New Drug
Application for Trudhesa included the results of the Phase 3,
open-label, pivotal safety study, STOP 301, which is the largest
longitudinal study ever conducted with DHE using nasal spray
delivery.1 More than 5,650 migraine attacks were treated over 24 or
52 weeks during the study. The primary objective of the study was
to assess the safety and tolerability of Trudhesa. Exploratory
objectives included efficacy assessments of migraine measures and a
patient acceptability questionnaire. In the trial, Trudhesa was
generally well tolerated and exploratory efficacy findings showed
it provided rapid, sustained, and consistent symptom relief. Unlike
some oral acute treatments that need to be taken within one hour of
attack onset to be most effective, the STOP 301 study reported
Trudhesa offered consistent efficacy even when taken late into a
migraine attack.2
There were no serious Trudhesa-related
treatment-emergent adverse events (TEAEs) observed in the STOP 301
study and the majority of TEAEs were mild and transient in nature.3
Some of the most frequently reported Trudhesa-related TEAEs (≥2%)
during the entire 52-week study period were nasal congestion
(17.8%), nausea (6.8%), nasal discomfort (6.8%), abnormal olfactory
test (6.8%) and vomiting (2.7%).4
In the STOP 301 study, patient-reported
exploratory efficacy findings reported that more than a third of
patients (38%) had pain freedom, two-thirds (66%) had pain relief,5
and more than half (52%) had freedom from their most bothersome
migraine symptom6 at two hours after their first dose of Trudhesa.
For one in six patients (16%), pain relief started as early as 15
minutes.7 Of patients who were pain free at two hours after their
first migraine attack, 98 percent were still pain free at 24 hours,
and 95 percent were still pain free through two days respectively,
during weeks 21-24.8 The great majority of patients (84%) reported
that Trudhesa was easy to use and preferred it over their current
therapy. 9
About MigraineApproximately 31
million adults in the U.S. are living with migraine,10 and there is
a need for more treatment options. In a survey of nearly 4,000 U.S.
patients using oral acute prescription medication for migraine, 96
percent said they were dissatisfied with at least one aspect of
their treatment—including lack of sustained relief, inconsistent
relief, and lack of relief from a rapid-onset attack. Nearly half
(48%) said they can still have pain two hours after taking
medication and 38 percent say their headache returns within 24
hours of getting relief.11 Additionally, there is a need for
non-oral routes of administration given the high prevalence of
gastrointestinal issues among people with migraine.
About Trudhesa® (dihydroergotamine
mesylate) Nasal SprayTrudhesa® is approved by the FDA for
the acute treatment of migraine with or without aura in adults in
the U.S. Using Impel’s proprietary POD® technology, Trudhesa gently
delivers DHE—a proven, well-established therapeutic8—quickly to the
bloodstream through the vascular-rich upper nasal space. Trudhesa
bypasses the gut and potential absorption issues, offering the
potential for rapid, sustained, and consistent relief without
injection or infusion, even when administered hours after the start
of a migraine attack.12
Trudhesa is a single use, drug-device
combination product containing a vial of DHE (4 mg DHE in a 1 mL
solution that is clear and colorless to faintly yellow) and a POD®
device. Prior to initiation of Trudhesa, a cardiovascular
evaluation is recommended. For patients with risk factors
predictive of coronary artery disease who are determined to have a
satisfactory cardiovascular evaluation, it is strongly recommended
that administration of the first dose of Trudhesa take place in the
setting of an appropriately equipped healthcare facility.
Trudhesa is designed to be self-administered.
Once assembled, Trudhesa should be primed before initial use by
releasing 4 sprays. A patient should use Trudhesa immediately after
priming. The recommended dose of Trudhesa is 1.45 mg administered
as two metered sprays into the nose (one spray of 0.725 mg into
each nostril). The dose may be repeated, if needed, a minimum of 1
hour after the first dose. A patient should not use more than 2
doses of Trudhesa within a 24-hour period or 3 doses within a 7-day
period. A patient should use or discard Trudhesa within 8 hours
once the vial has been opened or the product has been assembled. A
consumer assembly video is available
on www.TRUDHESA.com and please refer to the Instructions
for Use for more details.
The most common adverse reactions (incidence
≥2%) to Trudhesa were nasal congestion, nasal discomfort, nausea,
product taste abnormal, and product package associated injury. For
more information about Trudhesa and Full Prescribing
Information, including BOXED WARNING, please
visit, www.TRUDHESA.com.
About Impel Precision Olfactory Delivery
(POD®) Technology:Impel’s proprietary 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 Pharmaceuticals
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 a
broad range of 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 Dihydroergotamine Mesylate
(DHE)DHE was approved for the treatment of migraine in
19468 and has more than 70 years of therapeutic
use.8 Migraine treatment with DHE has demonstrated efficacy
independent of when the treatment is initiated.13 Unlike other
available treatments for migraine, DHE is known to bind to multiple
receptors theorized to be implicated in migraine onset and
duration.
Trudhesa® Indication and Important
Safety Information
IndicationTrudhesa® is used to
treat an active migraine headache with or without aura in adults.
Do not use Trudhesa to prevent migraine when you have no symptoms.
It is not known if Trudhesa is safe and effective in children.
Important Safety
Information
Serious or potentially life-threatening reductions in blood flow to
the brain or extremities due to interactions between
dihydroergotamine (the active ingredient in Trudhesa) and strong
CYP3A4 inhibitors (such as protease inhibitors and macrolide
antibiotics) have been reported rarely. As a result, these
medications should not be taken together. |
Do not use Trudhesa if you:
- Have any disease affecting your
heart, arteries, or blood circulation.
- Are taking certain anti-HIV
medications known as protease inhibitors (such as ritonavir or
nelfinavir).
- Are taking a macrolide antibiotic
such as clarithromycin or erythromycin.
- Are taking certain antifungals such
as ketoconazole or itraconazole.
- Have taken certain medications such
as triptans or ergot-type medications for the treatment or
prevention of migraine within the last 24 hours.
- Have taken any medications that
constrict your blood vessels or raise your blood pressure.
- Have severe liver or kidney
disease.
- Are allergic to ergotamine or
dihydroergotamine.
Before taking Trudhesa, tell your doctor
if:
- You have high blood pressure, chest
pain, shortness of breath, heart disease; or risk factors for heart
disease (such as high blood pressure, high cholesterol, obesity,
diabetes, smoking, strong family history of heart disease or you
are postmenopausal, or male over 40); or problems with blood
circulation in your arms, legs, fingers, or toes.
- You have or had any disease of the
liver or kidney.
- You are taking any prescription or
over-the-counter medications, including vitamins or herbal
supplements.
- You are pregnant, planning to
become pregnant or are nursing, or have ever stopped medication due
to an allergy or bad reaction.
- This headache is different from
your usual migraine attacks.
The use of Trudhesa should not exceed dosing
guidelines and should not be used on a daily basis. Serious cardiac
(heart) events, including some that have been fatal, have occurred
following the use of dihydroergotamine mesylate, particularly with
dihydroergotamine for injection, but are extremely rare.
You may experience some nasal congestion or
irritation, altered sense of taste, sore throat, nausea, vomiting,
dizziness, and fatigue after using Trudhesa.
Contact your doctor immediately if you
experience:
- Numbness or tingling in your
fingers and toes
- Severe tightness, pain, pressure,
heaviness, or discomfort in your chest
- Muscle pain or cramps in your arms
or legs
- Cold feeling or color changes in 1
or both legs or feet
- Sudden weakness
- Slurred speech
- Swelling or itching
The risk information provided here is not
comprehensive. To learn more, talk about Trudhesa with your
healthcare provider or pharmacist. The FDA-approved product
labeling can be found at www.Trudhesa.com or 1-800-555-DRUG. You
can also call 1-833-TRUDHESA (1-833-878-3437) for additional
information.
About Impel
PharmaceuticalsImpel Pharmaceuticals is a commercial-stage
pharmaceutical company developing transformative therapies for
people suffering from diseases with high unmet medical needs. Impel
offers treatments that pair its proprietary POD® technology
with well-established therapeutics. In September 2021, Impel
received U.S. FDA approval for its first product,
Trudhesa® nasal spray, which is approved in the U.S. for the
acute treatment of migraine with or without aura in adults. In
addition to Trudhesa, the Company continues to address patient
needs via licensing and partnerships.
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, the potential clinical benefits of Trudhesa®,
the market opportunities of Trudhesa within the migraine market,
the speed of uptake and market growth of Trudhesa, the
effectiveness of the Trudhesa sales force, the timing of
announcements of clinical results and clinical development
activities of Impel’s product candidates, and Impel’s 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 maintain regulatory approval of Trudhesa, its
ability to execute its commercialization strategy for Trudhesa, its
ability to develop, manufacture and commercialize its other 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, Trudhesa and the Impel logo are
registered trademarks of Impel Pharmaceuticals Inc. To learn more
about Impel Pharmaceuticals, please visit our website at
https://impelpharma.com.
Contact:
Media RelationsMelyssa WeibleElixir Health
Public RelationsPhone: (1)
201-723-5805Email: mweible@elixirhealthpr.com
Investor RelationsJanhavi MohiteStern Investor
RelationsPhone:
212-362-1200Email: janhavi.mohite@sternir.com
_________________________
1 On file at Impel2 Smith, TR, Winner, P, Aurora, SK, Jeleva, M,
Hocevar-Trnka, J, Shrewsbury, SB. STOP 301: A Phase 3, open-label
study of safety, tolerability, and exploratory efficacy of INP104,
Precision Olfactory Delivery (POD®) of dihydroergotamine mesylate,
over 24/52 weeks in acute treatment of migraine attacks in adult
patients. Headache. 2021; 00: 1– 13.
https://doi.org/10.1111/head.14184 3 Impel Neuropharma. (2020).
INP104-301. Table 3.4.5.4 Impel Neuropharma. (2020). Clinical Study
Report, Protocol No. INP104-301. Version 1.0. Tables 14.3.1.1.3b.5
Impel Neuropharma. (2020). INP104-301. Table 3.3.1.6 Impel
Neuropharma. (2020). INP104-301. Table 3.3.4.7 Shrewsbury SB,
Hoekman J, Jeleva M, Hocevar-Trnka J, Hoekman J, Shrewsbury SB, A
long term, open label study of Safety and Tolerability Of Precision
olfactory delivery of DHE in acute migraine (STOP 301): Clinical
Results, PainWEEK Live Virtual Conference Sept 11-13, 20208 Impel
Neuropharma. (2020). INP104-301. Table 3.3.6.9 Impel Neuropharma.
(2020). Clinical Study Report, Protocol No. INP104-301. Version
1.0. Tables 14.3.11.1a10 R. B. Lipton, M. E. Bigal, M. Diamond, F.
Freitag, M. L. Reed, W. F. Stewart. Migraine prevalence, Disease
Burden, and the Need for Preventive Therapy. Neurology
2007;68;343-349 DOI: 10.1212/01.wnl.0000252808.97649.2111 Impel
Neuropharma. (2020). INP104-301. Table 3.8.2.12 Aurora SK, et al. J
Headache Pain. 2013;14(Suppl 1):P143.13 Impel Neuropharma. (2020).
INP104-301. Table 3.3.6.
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