Oxcarbazepine XR Indication Expanded to Include Monotherapy for Partial-Onset Seizures

December 17, 2018

The treatment is the first approved novel, oral once-daily extended release formulation of oxcarbazepine for the treatment of partial-onset seizures in patients aged 6 years and older.

Jack Khattar, MBA

The FDA has approved a supplemental New Drug Application (sNDA) for oxcarbazepine extended-release (Oxtellar XR, Supernus Pharmaceuticals) to expand the medication’s indication beyond the current one of adjunctive therapy in the treatment of partial-onset seizures in adults and in children 6 to 17 years of age.1

The treatment is the first approved novel, oral once-daily extended release formulation of oxcarbazepine for the treatment of partial-onset seizures in patients aged 6 years and older. It is available in 150-mg, 300-mg, and 600-mg extended-release tablets.

“We are pleased with the timely approval of the expanded indication for Oxtellar XR. We look forward to launching Oxtellar XR in the first quarter 2019 as a new monotherapy treatment option for partial-onset seizures,” Jack Khattar, MBA, the president and chief executive officer of Supernus Pharmaceuticals, said in a statement. “We believe that expanding the indication to include monotherapy represents an additional growth opportunity for Oxtellar XR.”

In the previous submission to the FDA, clinical studies of the extended release formulation of the therapy showed that although the 1200-mg/day dose did not reach statistical significance in contrast with placebo, the concentration-response analyses revealed that it is an effective dosage. Patients on that dose (n = 122) showed a 38.2% reduction in seizure frequency (P = .078) compared to a 28.7% reduction with placebo. Likewise, the 2400-mg dose (n = 123) showed a 42.9% reduction in frequency of seizures (P = .003).2

In trials of the immediate release formulation, the effectiveness of oxcarbazepine as an adjunctive therapy for partial-onset seizures in adults was demonstrated at dosages of

600-mg/day, 1200-mg/day, and 2400-mg/day (divided twice-daily) in a randomized, double-blind, placebo-controlled trial. All dosages resulted in a statistically significant reduction in seizure frequency when compared to placebo (P <0.05).

The effectiveness of the 30-46 mg/kg/day dose, depending on baseline weight, as an adjunctive therapy for partial-onset seizures in pediatric patients was studied in a randomized, double-blind, placebo-controlled trial. In the single weight-based dosage group, oxcarbazepine resulted in a statistically significant reduction in seizure frequency when compared to placebo (P <0.05).

In terms of adverse events (AEs), the most commonly observed AEs (occurring in ≥5%) seen in approximately 1537 adults who were previously treated with antiepileptic medications were: dizziness, somnolence, diplopia, fatigue, nausea, vomiting, ataxia, abnormal vision, abdominal pain, tremor, dyspepsia, abnormal gait. Roughly 23% of these patients discontinued treatment because of an AE, with dizziness (6.4%), diplopia (5.9%), ataxia (5.2%), vomiting (5.1%), nausea (4.9%), somnolence (3.8%), headache (2.9%), fatigue (2.1%), abnormal vision (2.1%), tremor (1.8%), abnormal gait (1.7%), rash (1.4%), and hyponatremia (1.0%) as the leading reasons.3

For pediatric patients, the most commonly observed AEs observed in association with oxcarbazepine in these patients were similar to those seen in adults. About 11% of the 456 pediatric patients discontinued treatment because of an AE. The AEs most commonly associated with discontinuation were somnolence (2.4%), vomiting (2.0%), ataxia (1.8%), diplopia (1.3%), dizziness (1.3%), fatigue (1.1%), and nystagmus (1.1%).

REFERENCES

1. Supernus Announces FDA Approval of sNDA to Expand Oxtellar XR® Label to Include Monotherapy [press release]. Rockville, MD: Supernus Pharmaceuticals; Published December 14, 2018. globenewswire.com/news-release/2018/12/14/1667490/0/en/Supernus-Announces-FDA-Approval-of-sNDA-to-Expand-Oxtellar-XR-Label-to-Include-Monotherapy.html. Accessed December 17, 2018.

2. Oxtellar XR Prescribing Information. Oxtellar FDA label. Revised December 2018. oxtellarxr.com/assets/OxtellarXRPrescribingInformation.pdf. Accessed December 17, 2018.

3. DailyMed.

Oxacarbazepine

label. US National Library of Medicine. Updated August 8, 2014. dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=17325a80-fb9c-4a83-b4b4-98e0b999d852. Accessed December 17, 2018.