The Food and Drug Administration (FDA) has accepted for review the New Drug Application (NDA) for FT218, an investigational, once-nightly formulation of sodium oxybate, for the treatment of excessive daytime sleepiness and cataplexy in adults with narcolepsy.
The NDA submission is supported by data from the phase 3 REST-ON study (ClinicalTrials.gov: NCT02720744) that evaluated the efficacy and safety of FT218 in 212 patients with narcolepsy. Patients were randomly assigned to receive FT218 4.5g, 6.0g, 7.5g, 9.0g, or placebo once nightly for 13 weeks. The primary end points of the study included improvements on the maintenance of wakefulness test (MWT), clinical global impression of improvement (CGI-I) in daytime sleepiness, and mean weekly cataplexy attacks recorded on the Sleep and Symptom Daily Diary.
Results showed that patients treated with FT218 9g achieved highly significant and clinically meaningful improvement across all 3 end points compared with placebo at week 13:
- MWT (minutes): minutes): 10.82 vs 4.69, respectively; LS mean 6.13; P <.001.
- CGI-I (% of patients much/very much improved): 72% vs 31.6%, respectively; odds ratio 5.56; P <.001.
- Mean weekly cataplexy attacks: -11.51 vs -4.86; LS mean -6.65; P <.001.
Additionally, the 6g and 7.5g doses of FT218 demonstrated highly statistically significant, clinically meaningful improvements for all 3 end points compared with placebo (P <.001).
The 9g dose was found to be well tolerated with the most common adverse reactions reported being nausea (1.3%), vomiting (5.2%), decreased appetite (2.6%), dizziness (5.2%), somnolence (3.9%), tremor (1.3%), and enuresis (9%).
A Prescription Drug User Fee Act (PDUFA) target date of October 15, 2021 has been set for this application. “If approved, FT218 will be the first and only once-nightly oxybate medication, a significant advancement to the twice-nightly regimen that has been required for nearly 20 years,” said Greg Divis, CEO of Avadel.
Avadel Pharmaceuticals announces FDA acceptance of New Drug Application for FT218 in adults with narcolepsy for the treatment of excessive daytime sleepiness and cataplexy. [press release]. Dublin, Ireland: Avadel Pharmaceuticals; March 1, 2021.