WARREN, N.J., Nov. 2, 2018 /PRNewswire/ -- Aquestive
Therapeutics, Inc. (NASDAQ: AQST), a specialty pharmaceutical
company, today announced that the U.S. Food and Drug Administration
(FDA) approved SYMPAZAN™ (clobazam) oral
film for the adjunctive treatment of seizures associated with
Lennox-Gastaut syndrome (LGS) in patients 2 years of age or
older.1 SYMPAZAN is the first and only oral film
FDA-approved to treat seizures associated with LGS. Previously,
clobazam was marketed as ONFI® and offered in two formulations –
either tablet or oral suspension.2
"Aquestive Therapeutics is pleased to bring SYMPAZAN to the LGS
community," said Keith J. Kendall, Chief Executive Officer of
Aquestive Therapeutics. "Treating LGS can be difficult; patients
may have a hard time swallowing oral medications. We're optimistic
SYMPAZAN can help address unmet medical needs and be an important
treatment option for this patient population."
LGS is a severe form of epilepsy that begins in early childhood
and is characterized by multiple types of seizures and intellectual
disability.3 LGS patients often have difficulty
swallowing pills and large volume suspensions due to physical
limitations, behavioral or cognitive impact.4,5
Challenges with treatment administration can lead to uncertain and
inconsistent dosing, and increase the burden of care, particularly
for patients that may be combative or resistant to treatment.
5-8
Since FDA approval in 2011, clobazam tablets and oral suspension
(brand name ONFI®) have been a trusted adjunctive treatment for
LGS. In a Phase 3, randomized, double-blind, placebo-controlled
study of 238 LGS patients, clobazam tablets significantly reduced
the frequency of drop seizures (which involve falls) compared to
baseline by 41 percent (low dose) to 68 percent (high dose) vs. 12
percent for placebo (p<0.05 for all doses vs.
placebo).2,9 Please see more Important Safety
Information below, including the Boxed Warning on the risks
associated with concomitant use of opioids.
"Many LGS patients have a hard time swallowing pills and
suspensions. This can make administering medication hard for
caregivers," says Christina
SanInocencio, Executive Director of the LGS Foundation. "We
believe SYMPAZAN will be welcomed by patients and caregivers
impacted by LGS and searching for treatment solutions."
SYMPAZAN is a formulation based on Aquestive's proven PharmFilm®
technology. Multiple pharmacokinetic studies were conducted to
compare SYMPAZAN with ONFI. Based on the studies, SYMPAZAN oral
film was demonstrated to be bioequivalent to clobazam tablets and
have comparable safety profiles.1 Aquestive's clinical
development of SYMPAZAN followed the 505(b)(2) regulatory
pathway.
"SYMPAZAN is the beginning of a meaningful CNS franchise for
Aquestive," Kendall says. "We are actively working to advance more
redesigned, proprietary treatments that can offer meaningful
improvements for patients and caregivers who live with epilepsy and
other complex conditions."
Aquestive plans to commercialize SYMPAZAN in November, and has
engaged Ashfield Healthcare, a company specializing in
commercialization services, to build and train a highly qualified,
national sales force. The sales force will focus on pediatric
neurologists and epileptologists.
SYMPAZAN oral film is berry flavored and offered in 5 mg, 10 mg,
and 20 mg dosages to meet a range of LGS patient and caregiver
needs.1
About Aquestive Therapeutics
Aquestive
Therapeutics is a specialty pharmaceutical company committed
to identifying, developing and commercializing differentiated
products to address unmet medical needs. Aquestive
Therapeutics has a late-stage proprietary product pipeline
focused on the treatment of CNS diseases, and is working to advance
orally-administered complex molecules that it believes can be
alternatives to invasively-administered standard of care therapies.
As the leader in developing and delivering drugs via its PharmFilm®
technology, Aquestive Therapeutics also collaborates with
pharmaceutical partners to bring new molecules to market in
differentiated and highly-marketable dosage forms.
IMPORTANT SAFETY INFORMATION
BOXED WARNING:
RISKS FROM CONCOMITANT USE WITH OPIOIDS
Concomitant use of benzodiazepines and opioids may result in
profound sedation, respiratory depression, coma, and death.
- Reserve concomitant prescribing of these drugs for use in
patients for whom alternative treatment options are
inadequate.
- Limit dosages and durations to the minimum required.
- Follow patients for signs and symptoms of respiratory
depression and sedation.
CONTRAINDICATIONS
SYMPAZAN is contraindicated in patients with a history of
hypersensitivity to the drug or its ingredients. Hypersensitivity
reactions have included serious dermatological reactions.
WARNINGS AND PRECAUTIONS
Potentiation of Sedation from Concomitant Use with Central Nervous
System (CNS) Depressants
SYMPAZAN has a CNS depressant effect. Caution patients and/or
caregivers against simultaneous use with other CNS depressants or
alcohol as the effects of other CNS depressants or alcohol may be
potentiated.
Somnolence or Sedation
SYMPAZAN causes dose-related somnolence and sedation, which
generally begins within the first month of treatment and may
diminish with continued treatment. Monitor patients for somnolence
and sedation, particularly with concomitant use of other CNS
depressants. Caution patients against engaging in hazardous
activities requiring mental alertness, i.e., operating dangerous
machinery or motor vehicles, until the effect of SYMPAZAN is
known.
Withdrawal Symptoms
Abrupt discontinuation of SYMPAZAN should be avoided. The risk of
withdrawal symptoms is greater with higher doses. Withdraw SYMPAZAN
gradually to minimize the risk of precipitating seizures, seizure
exacerbation, or status epilepticus.
Serious Dermatological Reactions
Serious skin reactions, including Stevens-Johnson syndrome (SJS)
and toxic epidermal necrolysis (TEN), have been reported with
clobazam in both children and adults. Discontinue SYMPAZAN at the
first sign of rash, unless the rash is clearly not
drug-related.
Physical and Psychological Dependence
Patients with a history of substance abuse should be under careful
surveillance when receiving SYMPAZAN.
Suicidal Behavior and Ideation
AEDs, including SYMPAZAN, increase the risk of suicidal thoughts or
behavior in patients. Patients treated with SYMPAZAN should be
monitored for the emergence or worsening of depression, suicidal
thoughts or behavior, and/or any unusual changes in mood or
behavior. Inform patients, their caregivers, and families of the
increased risk of suicidal thoughts and behaviors. Advise them to
be alert for and report immediately to healthcare providers any
emergence or worsening signs and symptoms of depression, any
unusual changes in mood or behavior, or the emergence of suicidal
thoughts, behavior, or thoughts of self-harm.
ADVERSE REACTIONS
Adverse reactions (≥10% and more frequently than placebo) included
constipation, somnolence or sedation, pyrexia, lethargy, and
drooling.
DRUG INTERACTIONS
The concomitant use of benzodiazepines and opioids increases the
risk of respiratory depression. Limit dosage and duration of
concomitant use of benzodiazepines and opioids and follow patients
closely for respiratory depression and sedation. Concomitant use of
SYMPAZAN with other CNS depressants, including alcohol, may
increase the risk of sedation and somnolence. Caution patients
and/or caregivers against simultaneous use with other CNS
depressants or alcohol, as effects of other CNS depressants or
alcohol may be potentiated.
Hormonal contraceptives that are metabolized by CYP3A4;
effectiveness may be diminished when given with SYMPAZAN.
Additional non-hormonal forms of contraception are recommended when
using SYMPAZAN. Dose adjustment may be necessary of drugs
metabolized by CYP2D6 and of SYMPAZAN when co-administered with
strong CYP2C19 inhibitors (e.g., fluconazole, fluvoxamine,
ticlopidine).
USE IN SPECIFIC POPULATIONS
Pregnancy and Lactation: SYMPAZAN may cause fetal harm and should
only be used during pregnancy if the potential benefit justifies
the potential risk to the fetus. Infants born to mothers who have
taken benzodiazepines during the later stages of pregnancy can
develop dependence, withdrawal syndrome and symptoms suggestive of
floppy infant syndrome. SYMPAZAN is excreted in human milk. Because
of the potential for serious adverse reactions in nursing infants
from SYMPAZAN, discontinue nursing or discontinue the drug.
Encourage patients to call the toll-free number 1-888-233-2334 to
enroll in the Pregnancy Registry or visit
http://www.aedpregnancyregistry.org/.
You are encouraged to report negative side effects of
prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call
1-800-FDA-1088.
Please click here to see full Prescribing Information, including
Boxed Warning.
Forward-Looking Statement
This press release contains
forward-looking statements within the meaning of the Private
Securities Litigation Reform Act of 1995. Words such as
"anticipate," "believe," "could," "estimate," "expects," "intend,"
"may," "plan," "potential," "project," "will," "would," or the
negative of those terms, and similar expressions, are intended to
identify forward-looking statements. Such statements include, but
are not limited to, statements about regulatory approvals and
pathways, clinical trial timing and plans, the achievement of
clinical and commercial milestones, future financial and operating
results, business strategies, market opportunities, financing, and
other statements that are not historical facts.
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; the risks of delays in FDA approval
of our drug candidates or failure to receive approval; the risks
inherent in commercializing a new product (including technology
risks, financial risks, market risks and implementation risks and
regulatory limitations); development of our sales and marketing
capabilities; the rate and degree of market acceptance of our
product candidates; the success of any competing products; the size
and growth of our product markets; the effectiveness and safety of
our product candidates; risks associated with intellectual property
rights and infringement; unexpected patent developments; and other
risks and uncertainties affecting the Company including those
described in the "Risk Factors" section included in our
Registration Statement on Form S-1 declared effective by the SEC on
July 24, 2018. As with any
pharmaceutical product candidate under development, there are
significant risks with respect to the development, regulatory
approval and commercialization of new products. Given these
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. We assume no obligation to
update our forward-looking statements after the date of this press
release whether as a result of new information, future events or
otherwise, except as may be required under applicable law.
Media inquiries:
Christopher Hippolyte
christopher.hippolyte@syneoshealth.com
212-364-0458
Investor inquiries:
Stephanie Carrington
stephanie.carrington@icrinc.com
646-277-1282
References:
1.
|
Aquestive Data on
File. [SYMPAZAN Prescribing Information]. Warren, NJ: Aquestive
Therapeutics Inc; 2018.
|
2.
|
ONFI [package
insert]. Deerfield, IL: Lundbeck; 2011.
|
3.
|
Lennox-Gastaut
syndrome. National Institutes of Health.
https://ghr.nlm.nih.gov/condition/lennox-gastaut-syndrome.
Published 2018. Accessed November 1, 2018.
|
4.
|
Ogawa K, Kanemoto K,
Ishii Y, Koyama M, Sirasaka Y, Kawasaki J, Yamasaki S. Long-term
follow-up study of Lennox–Gastaut syndrome in patients with severe
motor and intellectual disabilities: with special reference to the
problem of dysphagia. Seizure. 2001; 10:197-202.
|
5.
|
LGS Foundation. About
Lennox-Gastaut Syndrome. Available at:
http://www.lgsfoundation.org/aboutlgs. Accessed November 1,
2018.
|
6.
|
Clobazam. Medline
Plus. https://medlineplus.gov/druginfo/meds/a612008.html. Accessed
October 25, 2018.
|
7.
|
Living with LGS.
About Lennox-Gastaut Syndrome. Available at:
http://www.lgsfoundation.org/livingwithlgs. Accessed November 1,
2018.
|
8.
|
Verrotti A., Coppola
G., Fiordaliso L., D'Egidio C., Loiacono G., Chiarelli F. New
antiepileptic drugs in the treatment of Lennox-Gastaut syndrome.
Journal of Pediatric Sciences. 2009;1:e16.
|
9.
|
Ng YT, Conry JA,
Drummond R, Stolle J, Weinberg MA; OV-1012 Study Investigators.
Randomized, phase III study results of clobazam in Lennox-Gastaut
syndrome. Neurology. 2011 Oct 11;77(15):1473-81.
|
View original
content:http://www.prnewswire.com/news-releases/aquestive-therapeutics-announces-us-food-and-drug-administration-fda-approval-for-sympazan-clobazam-oral-film-300742913.html
SOURCE Aquestive Therapeutics, Inc.