FDA Approves Clobazam (SYMPAZAN) Oral Film for Lennox-Gastaut Syndrome

The US Food and Drug Administration (FDA) has approved Aquestive Therapeutics’ clobazam (SYMPAZAN) oral film for the treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients aged 2 years or older. This approval marks the first and only oral film approved by the FDA for the treatment of seizures associated with Lennox-Gastaut Syndrome.

“Treating Lennox-Gastaut Syndrome can be difficult; patients may have a hard time swallowing oral medications,” said Keith J. Kendall, chief executive officer of Aquestive Therapeutics, in a recent statement. “We’re optimistic SYMPAZAN can help address unmet medical needs and be an important treatment option for this patient population.”

Earlier this past September 2018, clobazam was granted a tentative approval from the FDA for the same indication. Clobazam tablets and oral suspension (brand name ONFI) were previously approved by the FDA in 2011

Clobazam is a benzodiazepine and a proprietary formulation based on the company’s PharmFilm technology. The berry-flavored oral film is offered in 5 mg, 10 mg, and 20 mg dosages. In recent pharmacokinetic studies that compared clobazam oral film with clobazam tablets, investigators found the film to be bioequivalent to the tablets, with comparable safety.

Clobazam tablets demonstrated significant reductions in the frequency of drop seizures (which included falls) compared with baseline by 41% (low dose) to 68% (high dose) versus 12% for placebo (P<.05 for all doses versus. placebo) in 238 patients with Lennox-Gastaut Syndrome in a phase 3, randomized, double-blind, placebo-controlled trial.

Two multicenter controlled studies also established the effectiveness of clobazam for the adjunctive treatment of seizures associated with Lennox-Gastaut Syndrome, according to the prescription information.

In Study 1, a randomized, double-blind, placebo-controlled study that included a 4-week baseline period followed by a 3-week titration period and 12-week maintenance period, all dose groups of clobazam experienced statistically superior reductions in weekly drop seizures from this baseline (P≤.05) compared with baseline. (The observed effects appeared to be dose-dependent.)

In Study 2, a randomized, double-blind comparison study of high- and low-dose clobazam that included a 4-week baseline period followed by a 3-week titration period and 4-week maintenance period, the high-dose clobazam group experienced statistically significant greater reductions in seizure frequency compared with the low-dose group (median percent reduction of 93% versus 29%; P<.05).

Constipation, somnolence or sedation, pyrexia, lethargy, and drooling included observed adverse reactions (≥10% and more frequently than placebo).

“Many patients with Lennox-Gastaut Syndrome have a hard time swallowing pills and suspensions,” added Christina SanInocencio, executive director of the LGS Foundation. “This can make administering medication hard for caregivers. We believe SYMPAZAN will be welcomed by patients and caregivers impacted by Lennox-Gastaut Syndrome and searching for treatment solutions.”