FDA has approved clobazam, also named Onfi, from Lundbeck and Catalent Pharma Solutions, as adjunctive therapy for seizures associated with Lennox-Gastaut syndrome (LGS) in patients aged 2 years and older.

onfi clobazamThe drug Onfi is intended to treat a disease or condition that affects fewer than 200,000 people in the United States, therefore it was granted orphan drug designation by FDA.

The US regulators approval of Onfi was based on 2 multicenter controlled studies similar in terms of disease characteristics and prior treatment of patients, including a pivotal phase 3 study in 238 patients with a current or prior diagnosis of LGS. Named the CONTAIN Trial, the study’s primary end point was the percent reduction in the weekly frequency of drop seizures (atonic, tonic, or myoclonic), from the 4-week baseline period to the 12-week maintenance period. A phase 2 dose-ranging study was also conducted (n=68) that was consistent with results of the CONTAIN Trial.

“As an epileptologist treating patients with a variety of challenging seizure disorders, I’m aware of the need for new add-on therapies to address the severe and frequent seizures associated with LGS,” Joan A. Conry, MD, professor of neurology at Children’s National Medical Center in Washington, DC, and a principal investigator of the CONTAIN Trial, said in a Lundbeck press release. “Clobazam, now approved as Onfi, was shown to be effective as adjunctive therapy for reducing seizures associated with LGS, and its upcoming availability provides hope for additional seizure management to patients and their physicians, caregivers, and families.”

LGS usually begins before 4 years of age, and can be caused by a number of conditions, including brain malformations, severe head injuries, central nervous system infections, and inherited degenerative or metabolic conditions. In 30% to 35% of patients, no cause can be found. Patients commonly have frequent seizures of a wide variety, including tonic (stiffening of the body, upward deviation of the eyes, dilation of the pupils, and altered respiratory patterns), atonic (brief loss of muscle tone and consciousness, causing abrupt falls), atypical absence (staring spells), and myoclonic (sudden muscle jerks).

Most children with LGS experience some degree of impaired intellectual functioning or information processing, as well as developmental delays and behavioral disturbances.

The most common adverse reactions in the CONTAIN Trial included sleepiness or tiredness, fever, drooling, acting aggressive, irritability, lack of coordination, and constipation. The adverse reactions leading to discontinuation in ≥1% in the CONTAIN Trial in decreasing order of frequency included tiredness, sleepiness, lack of coordination, acting aggressive, fatigue, and difficulty sleeping.

Like other antiepileptic drugs, Onfi may increase the risk of suicidal thoughts or behaviors in a very small number of people taking the drug. Patients taking antiepileptic drugs should be monitored for depression, suicidal thoughts or behavior, and unusual changes in mood or behavior.

Onfi is an oral antiepileptic drug and will be available in 5-mg, 10-mg, and 20-mg tablets. Onfi is a 1,5 benzodiazepine. The exact mechanism of action for ONFI is not fully understood, but is thought to involve potentiation of GABAergic neurotransmission resulting from binding at the benzodiazepine site of the GABAA receptor. Onfi will be available in US pharmacies in early January and is a federally controlled Schedule 4 substance.

FDA is requiring that a medication guide be given to patients and caregivers when Onfi is dispensed.