This is the first oral film formulation of clobazam approved, highlighting the challenge of medication administration in patients with LGS, who often struggle due to physical, behavioral, or cognitive impacts.
Keith J. Kendall
The FDA has given the go-ahead for clobazam (Sympazan) for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients aged 2 years and older, making it the first and only oral film approved for this indication, according to its manufacturer, Aquestive Therapeutics.1
Clobazam was previously marketed as Onfi, offered in a pair of formulations: tablet and oral suspension. As patients with LGS often face limitations in their ability to swallow pills or large volume suspensions due to the physical, behavioral, or cognitive impacts of the condition, this new formulation seeks to address these issues, which can lead to uncertain or inconsistent dosing and increased burdens of care.
The 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.
"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."
The treatment first received approval from the FDA in 2011 and has been widely used since. In a phase 3 trial of 238 patients with LGS, the therapy significantly reduced the frequency of drop seizures compared to baseline by 41% with the lowest dose and 68% with the highest dose, compared to 12% for placebo (P
<.05, all doses vs. placebo).2
Additionally, responder rates of ≥50% were 31.6% with placebo compared to 43.4% (P
= .3383), 58.6% (P
= .0159), and 77.6% (P
<.0001) for clobazam 0.25-mg/kg, 0.5-mg/kg, and 1.0-mg/kg daily groups, respectively.
“Not only do the patients [with LGS or Dravet syndrome] have seizures, but they have such a severe type of seizure so frequently that the seizures may interfere with the development of the brain,” Steven S. Chung, MD, the executive director and program chair of the Neuroscience Institute and director of the Epilepsy Program at the Banner University Medical Center, told NeurologyLive
. “That kind of necessitates a more aggressive and more appropriate treatment early on, rather than to keep waiting and fussing with the different medications.”
Chung stressed the need for additional treatments for these patients, as they often struggle on medications, and can ultimately be quite refractive.
Aquestive noted that it plans to commercialize its clobazam formulation this month, and has engaged Ashfield Healthcare, a company specializing in commercialization services, to build and train a highly qualified, national sales force, focused on working with pediatric neurologists and epileptologists.
This approval comes on the heels of the FDA green-lighting a number of generic tablet formulations of clobazam, manufactured by companies including Breckenridge Pharmaceutical, Amneal Pharmaceuticals, and Upsher-Smith, among others. Amneal and Upsher-Smith received approval to market clobazam tablets and clobazam oral suspension, while Breckenridge will only market clobazam tablets.
According to industry sales data, the branded Onfi clobazam tablets generated annual sales of approximately $594 million throughout 12 months ending August 31, 2018, while clobazam oral suspension generated an estimated $255 million.
1. Aquestive Therapeutics Announces U.S. Food and Drug Administration (FDA) Approval for SYMPAZAN™ (clobazam) Oral Film [press release]. Warren, NJ: Aquestive Therapeutics; Published November 2, 2018. prnewswire.com/news-releases/aquestive-therapeutics-announces-us-food-and-drug-administration-fda-approval-for-sympazan-clobazam-oral-film-300742913.html. Accessed November 2, 2018.
2. Ng YT, Conry JA, Drummond R, et al. Randomized, phase III study results of clobazam in Lennox-Gastaut syndrome. Neurology. 2011;77(15):1473-81. doi: 10.1212/WNL.0b013e318232de76.