Aquestive Therapeutics, Inc. (NASDAQ: AQST), a pharmaceutical
company focused on developing and commercializing differentiated
products that address patients’ unmet needs and solve therapeutic
problems, today announced positive topline data from its
first-in-human Phase 1 PK study of AQST-109 sublingual film for the
delivery of epinephrine in the emergency treatment of allergic
reactions including anaphylaxis. Findings from this study support
AQST-109’s potential as the first orally administered epinephrine
treatment for anaphylaxis, with safety, tolerability, PK and
pharmacodynamics (PD) measures that fall within the target range of
standard of care autoinjectors such as epinephrine pens which
require patients or caregivers to inject into their thighs during
an emergency allergic reaction.
“These findings represent a critical step
forward in the development of our product candidate AQST-109 as the
first oral product aiming to treat anaphylaxis,” said Keith
Kendall, Chief Executive Officer of Aquestive. “The optimized PK/PD
profile of our epinephrine prodrug demonstrates that our oral
alternative to epinephrine injection can, in fact, match the PK
parameters of autoinjectors while lowering barriers to use and
improving convenience, ultimately resulting in better, often
life-saving outcomes for patients. Based on our review of published
literature, AQST-109 is the only non-injection form of epinephrine
to achieve a median Tmax of 15 minutes or less. We are encouraged
by these findings and continue to believe patients will embrace
this needle-free, user-friendly alternative.”
AQST-109 is a polymer matrix-based film that can
be applied sublingually (under the tongue) for the rapid delivery
of epinephrine. The product is similar in size to a postage stamp
and begins to dissolve on contact. No water or swallowing is
required for administration. The packaging for AQST-109 is thinner
and smaller than an average credit card, can be carried in a
pocket, and is designed to withstand weather excursions such as
exposure to rain and/or sunlight. Current stability data is
tracking favorably to support a two-year shelf life.
The Phase 1 randomized, single-ascending dose
(SAD) study was performed with AQST-109 in order to assess safety,
tolerability, PK, and PD profiles. The study was conducted in
Canada pursuant to a clinical trial application approved by Health
Canada. Subjects participating in the trial received, in ascending
fashion, sublingually administered doses of AQST-109 across four
different formulations. The four formulation compositions were
varied to assess critical absorption factors including drug loading
and the use of inventive excipients designed to influence
absorption, stability, and the conversion of the prodrug. A target
formulation (“formulation #2” highlighted below) was designed as
the lead candidate for the study.
Study Highlights
- Key clinical measures for
comparability to existing autoinjectors (Cmax, Tmax, and area under
the curve, or AUC) were within expected ranges for formulations 1,
2 (target), and 4
- Observed PD values were comparable
to existing data for autoinjectors
- AQST-109 was generally well
tolerated with no serious adverse events
Study Results |
AQST-109 (epinephrine prodrug sublingual film) 12
mg |
|
Comparable Data from Previous
& Published Studies |
Film Formulation # |
1 |
2 (Target) |
3 |
4 |
|
EpiPen®1 |
EpiPen®2 |
Auvi-Q®1 |
Dosings (n) |
6 |
8 |
6 |
7 |
|
135 |
10 |
67 |
Cmax (pg/mL) |
552 |
762 |
164 |
307 |
|
518 |
341 |
484 |
AUC 0-t (hr*pg/mL) |
634 |
603 |
329 |
303 |
|
560 |
328 |
526 |
Median Tmax (minutes) |
15 |
15 |
20 |
10 |
|
10 |
22 |
20 |
Tmax range (minutes) |
15-25 |
10-35 |
20-50 |
5-50 |
|
4-60 |
5-90 |
5-60 |
This study indicated that AQST-109 was absorbed
and rapidly converted to epinephrine with an observed median Tmax
of 15 minutes and an observed geometric mean Cmax of 762 pg/mL for
the target formulation. The findings for the target formulation are
comparable to published study results for both EpiPen and
Auvi-Q1234567. In addition, the target formulation had similar
median Tmax values at lower dose strengths (15 minutes and 17.5
minutes for the 6 mg and 9 mg doses, respectively, included in the
study). Based on the study results, Aquestive plans on continuing
development of the target formulation to take forward into a
pivotal PK study.
Safety data indicated that AQST-109 was
generally well tolerated with no serious adverse events (SAE’s),
significant medical events, or treatment-related severe adverse
events reported within the trial. All treatment-emergent adverse
events (TEAEs) deemed at least possibly related were mild to
moderate in nature across cohorts.
The PD markers measured changes from baseline in
heart rate, systolic blood pressure, and diastolic blood pressure.
The changes observed suggest a comparable effect for AQST-109 when
compared to autoinjectors in healthy volunteers.
David Fleischer, MD, Section Head, Pediatric
Allergy and Immunology at Children’s Hospital Colorado, Professor
of Pediatrics at University of Colorado School of Medicine,
commented, "An epinephrine delivery solution such as AQST-109 for
cases of severe life-threatening allergic reactions could address
the most important factor contributing to anaphylaxis fatality: the
therapeutic time window. The needle-free, pocket-sized, and
temperature safe attributes of this first-of-its-kind orally
administered prodrug will make it the preferred choice for parents
of children facing these risks.”
Aquestive has submitted its request for a
pre-investigational new drug (IND) meeting with the U.S. Food and
Drug Administration (FDA) and anticipates receiving a written
response from the FDA before the end of the year. In parallel,
Aquestive is on track to conduct a crossover study using an
adaptive design for AQST-109 in Canada beginning in the fourth
quarter 2021. It is anticipated that this study will establish a
final formulation and dose strength for commercial scale-up. The
study will include comparisons to 0.3 mg and 0.5 mg epinephrine
intramuscular (IM) manual injection and is anticipated to complete
in the first half of 2022.
A presentation of the results of the Phase 1 PK
study of AQST-109 is available on the events and presentation of
the investor section of the Company’s website at
https://investors.aquestive.com/events-and-presentations# and has
been filed with the SEC on Form 8-K.
About AnaphylaxisAnaphylaxis is
a potentially life-threatening systemic allergic reaction, with an
estimated incidence of 50 to 112 episodes per 100,000 people per
year. The frequency of hospital admissions for anaphylaxis has
increased 500-700% in the last 10-15 years. The most common causes
of reactions that can include anaphylaxis are medications, foods
(such as peanuts), and venom from insect stings. Epinephrine
injection is the current standard of treatment intended to reverse
the potentially severe manifestation of anaphylaxis, which may
include red rash, throat swelling, respiratory problems,
gastrointestinal distress and loss of consciousness.
About AQST-109Aquestive
Therapeutics is developing a sublingual (SL) film containing a
prodrug of epinephrine as an alternative dosage form to epinephrine
injection (1 mg/mL). The targeted indication for epinephrine
prodrug sublingual film is the same as that for epinephrine
injection in the emergency treatment of Type 1 allergic reactions,
including anaphylaxis.
Aquestive’s SL film contains a prodrug of
epinephrine incorporated into a polymer-based film matrix utilizing
its innovative PharmFilm® technology. Prodrugs are generally not
active moieties and require biotransformation to the parent
compound in vivo to allow for therapeutic activity. Treatment with
AQST-109 has been generally well-tolerated, with treatment-emergent
adverse events observed thus far being mild to moderate in
severity. There have been no serious adverse events observed.
About Aquestive
TherapeuticsAquestive Therapeutics is a pharmaceutical
company that applies innovative technology to solve therapeutic
problems and improve medicines for patients. The Company has
commercialized one internally-developed proprietary product to
date, Sympazan® (clobazam) oral film, has a commercial proprietary
product pipeline focused on the treatment of diseases of the
central nervous system, or CNS, and other unmet needs, and is
developing orally administered complex molecules to provide
alternatives to invasively administered standard of care therapies.
The Company also collaborates with other pharmaceutical companies
to bring new molecules to market using proprietary, best-in-class
technologies, like PharmFilm®, and has proven capabilities for drug
development and commercialization.
Forward-Looking
StatementCertain statements in this press release include
“forward-looking statements” within the meaning of the Private
Securities Litigation Reform Act of 1995. Words such as “believe,”
“anticipate,” “plan,” “expect,” “estimate,” “intend,” “may,”
“will,” or the negative of those terms, and similar expressions,
are intended to identify forward-looking statements. These
forward-looking statements include, but are not limited to,
statements regarding the potential for AQST-109 as the first orally
administered epinephrine prodrug for the treatment of anaphylaxis,
the advancement and related timing of AQST-109 through the
regulatory and development pipeline and clinical and business
strategies, market opportunities, and other statements that are not
historical facts. These forward-looking statements are subject to
the uncertain impact of the COVID-19 global pandemic on our
business including with respect to our clinical trials including
site initiation, patient enrollment and timing and adequacy of
clinical trials; on regulatory submissions and regulatory reviews
and approvals of our product candidates; pharmaceutical ingredient
and other raw materials supply chain, manufacture, and
distribution; sale of and demand for our products; our liquidity
and availability of capital resources; customer demand for our
products and services; customers’ ability to pay for goods and
services; and ongoing availability of an appropriate labor force
and skilled professionals. Given these uncertainties, the Company
is unable to provide assurance that operations can be maintained as
planned prior to the COVID-19 pandemic.
These forward-looking statements are based on
our current expectations and beliefs and are subject to a number of
risks and uncertainties that could cause actual results to differ
materially from those described in the forward-looking statements.
Such risks and uncertainties include, but are not limited to, risks
associated with the Company’s development work, including any
delays or changes to the timing, cost and success of our product
development activities and clinical trials for AQST-109 and our
other product candidates; risk of delays in FDA approval of
AQST-109, our drug candidate Libervant™ (diazepam) Buccal Film and
our other drug candidates or failure to receive FDA approval;
ability to address the concerns identified in the FDA’s Complete
Response Letter dated September 25, 2020 regarding the New Drug
Application for Libervant; risk of our ability to demonstrate to
the FDA “clinical superiority” within the meaning of the FDA
regulations of Libervant relative to FDA-approved diazepam rectal
gel and nasal spray products including by establishing a major
contribution to patient care within the meaning of FDA regulations
relative to the approved products as well as risks related to other
potential pathways or positions which are or may in the future be
advanced to the FDA to overcome the seven year orphan drug
exclusivity granted by the FDA for the approved nasal spray product
of a competitor in the U.S. and there can be no assurance that we
will be successful; risk that a competitor obtains FDA orphan drug
exclusivity for a product with the same active moiety as any of our
other drug products for which we are seeking FDA approval and that
such earlier approved competitor orphan drug blocks such other
product candidates in the U.S. for seven years for the same
indication; risk in obtaining market access for other reasons; risk
inherent in commercializing a new product (including technology
risks, financial risks, market risks and implementation risks and
regulatory limitations); risk of development of our sales and
marketing capabilities; risk of legal costs associated with and the
outcome of our patent litigation challenging third party at risk
generic sale of our proprietary products; risk of sufficient
capital and cash resources, including access to available debt and
equity financing and revenues from operations, to satisfy all of
our short-term and longer term liquidity and cash requirements and
other cash needs, at the times and in the amounts needed; risks
related to the outsourcing of certain marketing and other
operational and staff functions to third parties; risk of the rate
and degree of market acceptance of our product and product
candidates; the success of any competing products, including
generics; risk of the size and growth of our product markets; risks
of compliance with all FDA and other governmental and customer
requirements for our manufacturing facilities; risks associated
with intellectual property rights and infringement claims relating
to the Company’s products; risk of unexpected patent developments;
the impact of existing and future legislation and regulatory
provisions on product exclusivity; legislation or regulatory
actions affecting pharmaceutical product pricing, reimbursement or
access; claims and risks that may arise regarding the safety or
efficacy of the Company's products and product candidates; risk of
loss of significant customers; risks related to legal proceedings,
including patent infringement, investigative and antitrust
litigation matters; changes in government laws and regulations;
risk of product recalls and withdrawals; uncertainties related to
general economic, political, business, industry, regulatory and
market conditions and other unusual items; and other uncertainties
affecting the Company described in the “Risk Factors” section and
in other sections included in our Annual Report on Form 10 K, in
our Quarterly Reports on Form 10-Q, and in our Current Reports on
Form 8-K filed with the Securities Exchange Commission. Given those
uncertainties, you should not place undue reliance on these
forward-looking statements, which speak only as of the date made.
All subsequent forward-looking statements attributable to us or any
person acting on our behalf are expressly qualified in their
entirety by this cautionary statement. The Company assumes no
obligation to update forward-looking statements or outlook or
guidance after the date of this press release whether as a result
of new information, future events or otherwise, except as may be
required by applicable law.
PharmFilm®, Sympazan® and the Aquestive logo are
registered trademarks of Aquestive Therapeutics, Inc. All other
registered trademarks referenced herein are the property of their
respective owners.
Investor Inquiries:ICR Westwicke Stephanie
Carrington Stephanie.carrington@westwicke.com 646-277-1282
1 Dworaczyk D., Hunt A., Presented at American Academy of
Allergy, Asthma, Immunology (AAAAI) National Conference, March 16,
2020.
https://brynpharma.com/media/content/docs/comparative-delivery-poster.pdf.2
Aquestive Therapeutics, Study 160455, on file.3 Dworaczyk D., Hunt
A., J Allergy Clin Immunol Pract. 2021;147(2):(2 suppl) AB241
Presented at American Academy of Allergy, Asthma and Immunology
(AAAAI) National Conference; March 16, 2020; Accessed March 2,
20214 Worm M et al. Clin Transl Allergy. 2020:10:21.5 Duvauchelle T
et al. J Allergy Clin Immunol Pract. 2018;6(4):1257-12636 Breuer C
et al. Eur J Clin Pharmacol. 2013;69:1303-13107 Edwards ES et al.
Ann Allergy Asthma Immunol. 2013;111(2):132-137.
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