Cataplexy, Sleep Latency in Narcolepsy May Improve With Nightly Sodium Oxybate

Findings from 2 post-hoc analyses of the phase 3 REST-ON study showed that differing doses of once-nightly sodium oxybate, FT218, maintained significant reductions in cataplexy attacks and improved sleep latency among patients with narcolepsy compared with placebo.

As an investigational, extended-release, once-nightly formulation of sodium oxybate, FT218 has been cited to improve a significant barrier in adherence for patients with narcolepsy who rely on the sedation-inducing sodium oxybate. The current 2-dose formulation requires patients to wake up 2.5 to 4 hours after the first dose to take the second dose.

Previously, the 13-week, phase 3, double-blind, placebo-controlled, multicenter, randomized phase 3 REST-ON study showed the novel formulation was associated with significant improvements vs placebo on the coprimary end points of Maintenance of Wakefulness Test (MWT), Clinical Global Impressions of Improvement, and weekly cataplexy attacks at all 3 tested doses (6, 7.5, and 9 g; all P < .001).

Presented at the CHEST Annual Meeting 2021, the post hoc responder analyses REST-ON sought to further assess the improvement in mean sleep latency on the MWT and the improvement in the mean number of weekly cataplexy attacks.

Participants aged 16 or older with narcolepsy type 1 or 2 were randomized 1:1 to receive FT218 or placebo once nightly before bedtime (N = 212).

“Patients took 4.5 g for 1 week, 6 g for 2 weeks, 7.5 g for 5 weeks, and then 9 g for 5 weeks, with safety and efficacy assessments completed at the end of each dosing period,” added the researchers.

For the first study, the percentage of participants in each treatment arm who experienced 25% or greater, 50% or greater, 75% or greater, and 100% reductions from baseline in the mean number of weekly cataplexy attacks was determined.¹

At baseline, the mean (SD) number of weekly cataplexy attacks was 18.9 (8.7) and 19.8 (8.9) for the FT218 and placebo arms, respectively. In their findings, a significantly greater proportion of patients randomized to FT218 experienced reduction in the number of weekly cataplexy attacks vs the placebo arm across dosages:

• 6-g dose (week 3: ≥ 25% reduction, 68.5% vs 40.3%; P < 0.001; ≥ 50% reduction, 38.4% vs 20.8%; P < .05; ≥ 75% reduction, 23.3% vs 4.2%; P = .001; 100% reduction, 2.7% vs 0%; P = NS)
• 7.5-g dose (week 8: ≥ 25% reduction, 67.1% vs 43.1%; P < .001; ≥ 50% reduction, 53.4% vs 25.0%; P < .001; ≥ 75% reduction, 32.9% vs 8.3%; P < .001; 100% reduction, 6.8% vs 0; P < .05)
• 9-g dose (week 13: ≥ 25% reduction, 58.9% vs 41.7%; P = .001; ≥ 50% reduction, 49.3% vs 26.4%; P < .001; ≥ 75% reduction, 32.9% vs 15.3%; P < .01; 100% reduction, 11.0% vs 2.8%; P < .05).

For the second study, mean sleep latency was measured using the MWT across 5 trials, up to 30 minutes each.² “The percentage of participants in each treatment arm whose sleep latency improved 5 or more, 10 or more, 15 or more, and 20 or more minutes from baseline and percentage with a mean MWT of 30 minutes was determined.”

At baseline, the mean (SD) sleep latency on the MWT was 5.0 (3.1) and 4.7 (2.6) minutes for the FT218 and placebo arms, respectively. Moreover, the mean MWT equal to 30 minutes achieved in participants receiving FT218 6, 7.5, and 9 g vs placebo was 5.7% vs 0% (P < .05), 10.5% vs 1.3% (P < .05), and 13.2% vs 5.1% (P = .14), respectively.

Findings similarly showed significantly greater proportions of individuals in the FT218 group, across the dosages, who achieved increased mean sleep latency vs placebo:

• 6-g dose (week 3: ≥ 5 min, 57.5% vs 25.0%; P < .001; ≥ 10 min, 35.6% vs 9.1%; P < .001; ≥ 15 min, 18.4% vs 3.4%; P = .001; ≥ 20 min, 10.3% vs 1.1%; P < .01)
• 7.5-g dose (week 8: ≥ 5 min, 63.2% vs 28.2%; P < .001; ≥ 10 min, 43.4% vs 11.5%; P < .001; ≥ 15 min, 31.6% vs 3.8%; P < .001; ≥ 20 min, 15.8% vs 1.3%; P < .001)
• 9-g dose (week 13: ≥ 5 min, 66.2% vs 37.2%; P < .001; ≥ 10 min, 50.0% vs 19.2%; P < .001; ≥ 15 min, 32.4% vs 10.3%; P < .01; ≥ 20 min, 17.6% vs 6.4%; P < .05)

This year, the FDA granted approval to FT218's new drug application in adults with narcolepsy for the treatment of excessive daytime sleepiness and cataplexy, with a Prescription Drug User Fee Act (PDUFA) target action date of October 15, 2021—which has since been extended as the FDA noted the review is still ongoing.

References

1. Corser B, Ajayi A, Thorpy M, Seiden D, Dubow J, Bogan R. Cataplexy response with FT218, a once-nightly sodium oxybate: Post-hoc responder analyses from the phase 3 REST-ON clinical trial. CHEST. 2021;160(suppl 4):A2412-A2414. doi:10.1016/j.chest.2021.07.2087

2. Winkelman J, Ohayon M, Thorpy M, Bogan, et al. Sleep latency response with FT218, a once-nightly sodium oxybate: Post-hoc responder analyses from the phase 3 REST-ON clinical trial. CHEST. 2021;160(suppl 4):A2426-A2428. doi:10.1016/j.chest.2021.07.2097