Breaking News
November 19, 2018 - Short Interpregnancy Intervals Tied to Adverse Outcome Risk
November 19, 2018 - New mothers’ breastfeeding pain can affect infant health
November 19, 2018 - Stanford Medicine magazine reports on ways digital technology is transforming health care | News Center
November 19, 2018 - Human drugs alter cricket personality
November 19, 2018 - Insilico Medicine to introduce ‘Cure a disease in a year’ program at Biodata World Congress 2018
November 19, 2018 - Experts debate over whether gut or brain is more important in regulating appetite
November 19, 2018 - Playing on fear and fun, hospitals follow pharma in direct-to-consumer advertising
November 19, 2018 - Low-Carb Diets May Work By Boosting Calorie Burn
November 19, 2018 - Key molecule responsible for learning and memory discovered
November 19, 2018 - New blood test developed for early diagnosis of ovarian cancer
November 19, 2018 - Researchers identify molecule to fight myotubular myopathy
November 19, 2018 - New solution to stop spread of brain cancer
November 19, 2018 - Immune cells trigger OCD-like behaviour in multiple sclerosis, study finds
November 19, 2018 - Scientists equip new virus that kills carcinoma cells with protein
November 19, 2018 - Novel approach could provide painless, efficient alternative for treating eye diseases
November 19, 2018 - Protein in cell membranes of sperm plays key role in finding their way to eggs
November 19, 2018 - Parents who decline flu vaccination for their child may be exposed to limited information
November 19, 2018 - Mirati Presents Data From Ongoing Phase 2 Clinical Trial Of Mocetinostat In Combination With Durvalumab At The SITC 33rd Annual Meeting
November 19, 2018 - FDA warns of common diabetes meds’ link to dangerous genital infection
November 19, 2018 - New methods for preserving shoulder function, quality of life in breast cancer patients
November 19, 2018 - Surprising discovery about BH4 may rekindle interest in once-promising pathway
November 19, 2018 - Nabriva Therapeutics Completes Submission of New Drug Application to U.S. Food and Drug Administration for Intravenous Contepo to Treat Complicated Urinary Tract Infections
November 19, 2018 - Beating breast cancer only to die of opioid use – a sad Appalachian story
November 19, 2018 - Workplace bullying or violence linked to higher risk of cardiovascular problems
November 19, 2018 - Changes in Risk Indicators of MetS Severity Tied to T2DM Risk
November 19, 2018 - ‘Game-changing’ skin sensor could improve life for a million hydrocephalus patients
November 19, 2018 - Alcohol ads on social media sites with pro-drinking comments increase desire to drink
November 19, 2018 - Neural networks could replace marker genes in RNA sequencing
November 19, 2018 - Obese adolescents feel less food enjoyment than those with normal weight, study reveals
November 18, 2018 - Goodbye ‘Gluten-Free’? Celiac Disease Vaccine May Make It Possible
November 18, 2018 - Skin ages when the main cells in the dermis lose their identity and function
November 18, 2018 - Rainforest vine compound makes pancreatic cancer cells susceptible to nutrient starvation
November 18, 2018 - A new mechanism in the control of inflammation
November 18, 2018 - Age-related decline in abstract reasoning ability predicts depressive symptoms over time
November 18, 2018 - Scientists succeed in increasing stability, biocompatibility of light-transducing nanoparticles
November 18, 2018 - Sugar, a ‘sweet’ tool to understand brain injuries
November 18, 2018 - Pharmacist-Led Effort Cuts Inappropriate Rx in Older Adults
November 18, 2018 - Novel discovery could lead to new cancer, autoimmune disease therapy
November 18, 2018 - AHA and ADA launch new initiative to help people with type 2 diabetes reduce heart disease risk
November 18, 2018 - Balanced production of pro and anti-inflammatory cytokines at two years of age protects against malaria
November 18, 2018 - New pharmacological agent shows promise for prevention of heart rhythm disorders
November 18, 2018 - All That Social Media May Boost Loneliness, Not Banish It
November 18, 2018 - Scientists shine new light on link between obesity and cancer
November 18, 2018 - Risk factors for cardiovascular disease closely track with changes in diet patterns
November 18, 2018 - Biogen Scoops Sixth Prix Galien Award with UK Win for Life-Changing Rare Disease Medicine
November 18, 2018 - Detectable HIV-1 in treated human liver cells found to be inert
November 18, 2018 - Using light to control crucial step in embryonic development
November 18, 2018 - Unusual case of father-to-son HIV transmission reported
November 18, 2018 - FDA Approves Aemcolo (rifamycin) to Treat Travelers’ Diarrhea
November 18, 2018 - Poverty blamed on widening north-south gap in young adult deaths in England
November 18, 2018 - Progress in meningitis lags far behind other vaccine-preventable diseases, analysis shows
November 18, 2018 - Consensus Statement Issued on Management of Foot, Ankle Gout
November 18, 2018 - Fine particle air pollution is a public health emergency hiding in plain sight
November 18, 2018 - In-hospital mortality higher among patients with drug-resistant infections
November 17, 2018 - Research shines new, explanatory light on link between obesity and cancer
November 17, 2018 - FIND explores new diagnostic assays for confirmatory HCV diagnosis in community settings
November 17, 2018 - Tracking Preemies’ Head Size May Yield IQ Clues
November 17, 2018 - Scientists call for unified standards in 3-D genome and epigenetic data
November 17, 2018 - Lab Innovations 2018 has beaten all records by attracting 3,113 attendees
November 17, 2018 - New strategy to hinder emergence of antimicrobial-resistant pathogens
November 17, 2018 - Sexuality education before age 18 may reduce risk of sexual assault in college
November 17, 2018 - Reducing cellular proliferation could help deplete HIV reservoir and lead to a functional cure
November 17, 2018 - New model of FSHD could be useful to study effectiveness of experimental therapeutics
November 17, 2018 - FDA approves antibacterial drug to treat travelers’ diarrhea
November 17, 2018 - Lab Innovations 2018 confirmed as a major hit with visitors, exhibitors and speakers
November 17, 2018 - Largest parasitic worm genetic study hatches novel treatment possibilities
November 17, 2018 - UCLA biologists uncover how head injuries can lead to serious brain disorders
November 17, 2018 - Static and dynamic physical activities offer varying protection against heart disease
November 17, 2018 - Obesity significantly increases risk of Type 2 diabetes and coronary artery disease
November 17, 2018 - New method to analyze cell membrane complexes could revolutionize the way we study diseases
November 17, 2018 - Researchers show how proteins interact in hypoxic conditions to facilitate mitochondrial fission
November 17, 2018 - People with rare cancers can benefit from genomic profiling, shows research
November 17, 2018 - NIH awards over $1.8 million to husband-and-wife doctors to test new breast cancer approach
November 17, 2018 - Four-in-one antibody used to fight flu shows promise in mice
November 17, 2018 - New approach allows pathogens to be starved by blocking important enzymes
November 17, 2018 - Higher body mass index could cause depression even without health problems
November 17, 2018 - Protein which plays role in sensing cell damage serves as new target to treat pulmonary hypertension
November 17, 2018 - FDA Approves Adcetris (brentuximab vedotin) in Combination with Chemotherapy for Adults with Previously Untreated Systemic Anaplastic Large Cell Lymphoma or Other CD30-Expressing Peripheral T-Cell Lymphomas
November 17, 2018 - ID specialist input improves outcomes for outpatient parenteral antimicrobial therapy
November 17, 2018 - UT Southwestern scientists selected to receive 2019 Edith and Peter O’Donnell Awards
FDA Approves Sympazan (clobazam) Oral Film for Adjunctive Treatment of Seizures Associated with Lennox-Gastaut Syndrome

FDA Approves Sympazan (clobazam) Oral Film for Adjunctive Treatment of Seizures Associated with Lennox-Gastaut Syndrome

image_pdfDownload PDFimage_print

FDA Approves Sympazan (clobazam) Oral Film for Adjunctive Treatment of Seizures Associated with Lennox-Gastaut Syndrome

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.

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.

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.

SOURCE Aquestive Therapeutics, Inc.

Posted: November 2018

Sympazan (clobazam) FDA Approval History

Tagged with:

About author

Related Articles